I recently wrote an article that introduces the Open Cures initiative and explains the backdrop of medical research and regulation that makes Open Cures - or something very much like it - absolutely necessary. The piece is presently published at h+ Magazine:

You may recognize me as the author-slash-editor of Fight Aging!, a long-running news and advocacy site focused on progress towards reversal of aging and engineering longer human lives. There is more to progress in the general sense than just the underlying science, however, and with that in mind I recently announced the launch of Open Cures, a volunteer initiative with the aim of greatly speeding up the development of clinical applications of longevity science. Participation is open to anyone who can help with the goals listed in the Open Cures roadmap: for example, we're presently looking for life science writers and people familiar with the medical tourism industry, amongst others.

But why, in this age of biotechnology and accelerating progress, it is even necessary to build an organization to help speed matters along? What is the roadblock that stands in the way of the clinical development of longevity-enhancing biotechnology?

I encourage you to read it all: it's a fairly concise outline as to why developing the scientific tools of rejuvenation is not enough in and of itself to win the game. We also have to ensure that clear paths exist for commercial development of legitimate treatments for aging - which is far from the case today:

Aging is not a disease, per the FDA - and therefore, no one is legally permitted to treat aging in humans with biotechnology in the US.

A fair number of well funded groups have been burning money and time in well-thought, well-connected efforts to change the FDA: to make it less hostile to progress, to enable therapies to come to market more rapidly (or in some cases at all). This has been going on for years - see FasterCures, for example - but has come to nothing. Changing the FDA is not the way forward: instead we need to work around it - and that is the Open Cures methodology:

Open Cures is a young volunteer initiative, formed in mid-2011 to work upon a grand long term vision: to orchestrate the clinical development of therapies already demonstrated to either extend life or reverse narrow aspects of aging in mice, and which may be capable of doing the same for humans. A dozen or more such biotechnologies presently languish with little effort devoted to their clinical development, because regulatory bodies such as the FDA forbid treatments for aging.

The following roadmap outlines a series of overlapping phases of development by which Open Cures volunteers can change this present environment and its hostility to the development of effective therapies to treat degenerative aging. The Open Cures vision is of a bridge built between the undeveloped biotechnologies of rejuvenation produced in US and European laboratories and the overseas developers who could usher these technologies into the clinic for human trials.

An open access review of work on regenerative medicine based on embryonic stem cells: "The prospect of repairing or replacing damaged, dysfunctional or missing cells with new functional cells has shifted the therapeutic paradigm toward restoring tissue function in individuals affected with aging-associated diseases. The primary candidate for the development of these therapies is stem cells, particularly human embryonic stem cells (hESC), which have the capacity to self-renew indefinitely and differentiate into all tissue-specific cell types... In this review, we will describe the derivation, maintenance, and properties of pluripotent hESCs. We will also outline the methods used to induce the generation of specific cell types from hESCs, with primary focus on cell types that are applicable in understanding the pathology, as well as a potential source of cell-based therapies, in aging-associated diseases. ... As cell replacement therapies are envisioned and realized, their use in the treatment of aging-associated diseases becomes a compelling prospect. hESCs provide much promise as a potential tool in designing such therapies, as well as in drug discovery. It is clear that there are still major scientific challenges as well as ethical and legislative issues that must be addressed. However, it is encouraging to see that clinical trials involving the use of hESCs have begun, and that extensive efforts are underway to efficiently, successfully, and safely differentiate hESCs into specific cell types. These studies will pave the way toward leveraging the therapeutic benefit of hESCs for regenerative medicine, particularly in aging-associated diseases."

Link: http://www.impactaging.com/papers/v3/n5/full/100328.html

As you might recall, manipulation of RasGrf1 extends life in mice: "The most intriguing finding was that the complete elimination of normal RasGrf1 increased both average and maximal longevity independent of a role in cancer. We found this to be surprising ... The effect of RasGrf1 deletion on aging, which is also accompanied by lower frailty and retention of motor control, appears to be mediated by greater protection against oxidative damage as observed by lower brain lipid peroxidation, liver protein oxidation and maintenance of the brain and liver glutathione redox potential. We must note that the use of malondialdehyde levels as a measure of overall lipid peroxidation in whole tissues is rather suspect and subject to numerous artifacts; nevertheless, the approximate 25% lower MDA levels in RasGrf-/- mice (in comparison with wild-type mice) were significant. ... it is impressive that the old RasGrf1 deletion mutants exhibited almost 30% lower levels of oxidized liver proteins than did the young wild-type mice. ... RASGRF1 is expressed in pancreatic β-cells where it regulates β-cell mass. So the effects on glucose metabolism is unsurprising. RasGrf1 is also expressed in the hippocampus and hypothalamus is involved in learning and memory. So, one wonders how a human without RasGrf1 would be able to do those functions and whether living longer and stronger might be accompanied by not remembering why one cared. ... Another interesting point raised by the authors is that RasGrf1,which is an exclusively paternal allele imprinted gene, suggests that only the male parent determines the effect of this gene's expression on longevity. In several ways, the RasGrf1-/- mice metabolically resemble mice fed a calorie-restricted diet. One exciting outcome of these studies is that RasGrf1 may be a potential target for design of agents that prolong lifespan and healthspan without the obvious difficulty of restricting caloric intake."

Link: http://www.impactaging.com/papers/v3/n5/full/100331.html

As I've noted in the past, one of the challenges that faces present day cryonics as an industry is that it requires a measure of proactive organization and ongoing effort on the part of customers. You can't just sign up for cryopreservation, pay your monthly dues, and let matters coast along unattended - not if you want things to go smoothly when the service is needed. All sorts of obstacles, both organizational and bureaucratic, can rear their ugly heads: arranging your own cryopreservation is less a matter of agreeing to go to a party than it is a matter of agreeing to be the host and organizer of a party.

This, of course, greatly reduces the range of people who are willing to sign up for cryonics - no-one likes inconvenience, and there's a certain irrationality when it comes to using (or avoiding) inconvenient services that may save your life one day. There is, I think, an opportunity here for some service provider to emerge and offer a more managed cryonics membership, in which these issues are are smoothed away in return for a higher membership cost. But perhaps that lies ahead, in a future in which the cryonics industry grows much larger than it is today.

But back to the challenges: many of them are legal in nature, or involve the intruding hand of local government. For example, a coroner may wish to conduct an autopsy, which will certainly spoil the chance of a successful cryopreservation. Working through the legal niceties to ensure that the local coroner's office cannot do this is one amongst many line items that must be addressed - and addressed well, as it's not as though you will be up and able to talk your way through any problems that happen at the time. But here are a couple of recent articles that address some of these legal issues:

Medico-Legal Aspects of Human Cryopreservation Optimization

One aspect of cryonics optimization planning that has received little attention to date is to develop legal strategies to deal with medical and legal issues surrounding one's death, terminal illness, and the dying phase. In this memo I will outline some of the most important medical and medico-legal issues, how cryonicists could benefit from recognizing them, and suggest some legal and practical solutions.

...

It has become clear that in the case of many topics we would all benefit from uniform and effective language. The next step is to translate the concerns discussed in this document in clear legal language so that templates can be offered to all members of cryonics organizations to draft their own Living Will and Advance Directives. One potential problem of such a general template is that it may not conform to state regulations and needs additional tweaking to make it valid in the state where the person lives.

Advance Directives and Transhumanism

Advance directives are documents which give guidance on what should be done when your health deteriorates to the point where you can no longer make decisions for yourself. Sadly, these documents are often neglected by the general public until it is too late, but it's even more crucial for transhumanists to think about and complete these documents.

...

Of course, ideally in near-death scenarios you'd have the option of either vitrification
and cryonic preservation or brain plastination. Unfortunately, you can't yet use advance directives to specify that you'd like to undergo such procedures while still alive, when they would be most effective. But you can use advance directives in an attempt to minimize the likelihood of end of life care interfering with a successful cryopreservation. For example, you could specify that if your condition is deemed irrecoverable and keeping you alive could incur further neuronal damage, your body should be allowed to de-animate.

...

We need to work towards a time when individuals do have the legal option of brain plastination or cryopreservation while still alive. But until such a time, the more people who make informed decisions about their end of life care, the better.

No-one likes to think about their own impending death - but if you want to take advantage of the opportunity offered by cryonics, the chance at something other than oblivion after you die, then you'll have to plan and organize effectively.

Here's an interesting study that might place some upper bounds on the benefits of exercise accruing to longevity by looking at a cohort of the most highly trained and fit athletes. There are potential selection effects here, however - it's possible that only those already predisposed towards longevity on the grounds of general resiliency tend to become highly trained and fit athletes: "It is widely held among the general population and even among health professionals that moderate exercise is a healthy practice but long term high intensity exercise is not. The specific amount of physical activity necessary for good health remains unclear. To date, longevity studies of elite athletes have been relatively sparse and the results are somewhat conflicting. The Tour de France is among the most gruelling sport events in the world, during which highly trained professional cyclists undertake high intensity exercise for a full 3 weeks. Consequently we set out to determine the longevity of the participants in the Tour de France, compared with that of the general population. We studied the longevity of 834 cyclists from France, Italy and Belgium who rode the Tour de France between the years 1930 and 1964. Dates of birth and death of the cyclists were obtained on December 31 2007. We calculated the percentage of survivors for each age and compared them with the values for the pooled general population of France, Italy and Belgium for the appropriate age cohorts. We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners. Our findings underpin the importance of exercising without the fear that becoming exhausted might be bad for one's health."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21618162

Some mainstream media attention for the work of the SENS Foundation: "Rather than simply slowing ageing down, which is what most people have been focused on, we are interested in reversing ageing. So taking people who are already in middle age or older and [getting them back to] the same state of health as a young adult. ... [SENS Foundation co-founder Aubrey de Grey was in Dublin] to talk about how he thinks science will achieve that. ... So how do you reverse ageing? The basis of de Grey's argument is that our metabolism, that complex biochemical orchestra that keeps our bodies running, has side effects that cause damage in the long term. ... The big insight that governs our work is that we can classify these many different types of damage into just seven major categories. And within each category, there is a particular approach that seems promising to not simply slow it down but repair the damage, so we have less of it than we had before the therapy was started. ... The research is at a basic stage, and therapies for use on humans are decades away, according to de Grey. He considers the theme that looks to tackle junk that accumulates between cells to be the most advanced. That's an area being looked at by Dr Brian O'Nuallain, who has just left University College Dublin for Harvard Medical School, and Brigham and Women's Hospital. He is starting work on a Sens-funded project into an age-associated condition called senile systemic amyloidosis. One aim is to develop an antibody that will pick up when a protein called transthyretin clumps abnormally in heart tissue, which can lead to organ failure. Being able to diagnose this early would maximise the beneficial effects of future therapies for the incurable condition,"

Link: http://www.irishtimes.com/newspaper/features/2011/0525/1224297699236.html

FIGHT AGING! NEWSLETTER
May 30th 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- Countries, Medical Tourism, Law: Research Volunteers Wanted
- Senescent Cells Make Lungs More Vulnerable
- Three Parallel Tracks
- The Most Important Debate in Longevity Science
- Discussion
- Latest Headlines from Fight Aging!

COUNTRIES, MEDICAL TOURISM, LAW: RESEARCH VOLUNTEERS WANTED

I am looking for volunteers to help assemble some foundational information for the Open Cures initiative:

http://www.fightaging.org/archives/2011/05/countries-medical-tourism-law-a-research-project-for-the-open-cures-initiative.php

"[Later phases of the Open Cures initiative involve] building relationships with the medical tourism industry and developers outside the US. At present I have just as little an idea of the fine details of that process as you do - but discovery is half the challenge in building any initiative. This is where research and volunteers come into the picture. There is a great deal of very useful information out there in various websites and publications that I would like to see assembled into one place - or at least the references to it all assembled in one place. This is light research work that any smart person with an internet connection can undertake, and it can take place in parallel to other foundational work for Open Cures - and be accomplished piecemeal by many different people. Many hands make light work."

So I am looking for volunteers to help assemble basic information on the state of medical tourism on a country by country basis, listing out the major players in the industry, and itemizing data on medical investment and development. Take a look at the link above for an initial list of line items. This may be a case of cleverly finding out that someone in the medical tourism industry has done much of this work already, but I think there's a little more to it than that. To my mind the eligible countries include much of the Asia-Pacific region, India, and a few others - but validating that list with real numbers is one of the tasks on the table.

SENESCENT CELLS MAKE LUNGS MORE VULNERABLE

Senescent cells accumulate in our tissues with age: these are cells that become damaged or worn, fall out of the normal cell cycle, but fail to self-destruct as they are programmed to do. The immune system should hunt down and destroy these errant cells, but it too becomes worn with age. Growth in the senescent cell population has direct, material effects on health - such as this:

http://www.fightaging.org/archives/2011/05/senescent-cells-make-lungs-more-susceptible-to-infection.php

"The researchers found that when it comes to aging and pneumonia, one bad apple can ruin the barrel. Lung cells that were supposed to die due to DNA damage - but didn't - were 5 to 15 times more susceptible to invasion by pneumonia-causing bacteria. These bad apples also increased the susceptibility of normal cells around them. Both age and [pneumonia] are associated with senescent cells, which are unable to die due to dysregulated function. These cells have increased levels of proteins that disease-causing bacteria stick to and co-opt to invade the bloodstream. The cells also spew out molecules that increase inflammation, and make normal cells nearby do the same.

"How will we deal with senescent cells with near future biotechnology? The likely answer is through the use of technologies pioneered in cancer research: precision cell-killing strategies that can locate and destroy very specific types of cell without harming any other cell types. These may use nanoparticles or they may involve training the immune system to attack senescent cells with vigor, but both paths have been demonstrated effective in the laboratory."

THREE PARALLEL TRACKS

There are three parallel tracks along which the future development of longevity science must progress, and we'll reach the end goal only as rapidly as the slowest of the three tracks moves.

http://www.fightaging.org/archives/2011/05/three-parallel-tracks.php

"1) Science: The most obvious of the tracks is that the technologies of rejuvenation must be developed. We can see what the form that these technologies must take: damage repaired, waning cell populations renewed, waste byproducts broken down and removed, cancer thwarted. Initiatives like SENS can describe the needed procedures in great detail, at the level of cells and molecular machinery, as we truly are within a tantalizingly close reach of their creation.

"2) Clinical Development: Taking the output of the scientific method and turning it into reliable, affordable, widely available technology is no less a challenge than scientific progress. It is fraught with risk, and the stakes are much higher: the cost of developing new science is small in comparison to the costs of building an industry. Moving from one technology demonstration and a few patients to a technology used by hundreds of thousands of patients around the world is a massive undertaken in risk, development, innovation, and cutthroat competition.

"3) Persuasion: You can change the world with ten thousand people who think the same way as you do, that much is true, but it will be hard and it will take a long, long time. In the end, you'll only succeed by convincing hundreds of thousands more to contribute their support. It does't require all the world to agree with you. Half a percentage point of the world's population is hundreds of millions of people. Markets with hundreds of millions of customers are worth billions of dollars, even though they gain only a tiny, tiny fraction of the attention and expenditure of those people - and billions of dollars would be more than enough to fund the first emergence of true rejuvenation biotechnology."

THE MOST IMPORTANT DEBATE IN LONGEVITY SCIENCE

Will the research community focus on slowing aging through metabolic manipulation or reversing aging through repair of damaged biological machinery? This is what will determine whether we in fact live far longer healthy lives:

http://www.fightaging.org/archives/2011/05/the-latest-rejuvenation-research-and-the-most-important-debate.php

"It is likely to be easier and less costly to produce rejuvenation therapies than to produce a reliable and significant slowing of aging. A rejuvenation therapy doesn't require a whole new metabolism to be engineered, tested, and understood - it requires that we revert clearly identified changes to return to a metabolic model that we know works, as it's used by a few billion young people already. Those rejuvenation therapies will be far more effective than slowing aging in terms of additional years gained, since you can keep coming back to use them again and again. They will also help the aged, who are not helped at all by a therapy that merely slows aging.

"Whatever the course of research, the first resulting widespread therapies to significantly extend healthy human life are two or more decades away. Most of us will be old before the second generation of better and more reliable therapies emerges thereafter. Thus repair strategies for ongoing research must come to dominate the funding landscape over the next decade if we are to see meaningful progress in engineered human longevity within our lifetimes. Slowing aging will be of little use to us by the time it becomes available.

"All of this means that this scientific debate is far too important for all of us to refrain from participation. We should all absolutely dive in and loudly offer our own opinions on the topic, and help the researchers and fundraisers focused on repair biotechnologies succeed in their aims: it is, after all, the future of all our lives on the line."

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

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LATEST HEADLINES FROM FIGHT AGING!

CONSCIENTIOUSNESS AND LONGEVITY
Friday, May 27, 2011
http://www.fightaging.org/archives/2011/05/conscientiousness-and-longevity.php
The conclusion of the researchers in this study is interesting, leaning as it does towards cognitive function rather than better implementation of health practices - though both general health and cognitive function are linked via mechanisms such as blood vessel health in the brain. Untangling the knots of many interrelated correlations in such complex things as human beings isn't easy: "Conscientious individuals tend to experience a number of health benefits, not the least of which being greater longevity. However, it remains an open question as to why this link with longevity occurs. The current study tested two possible mediators (physical health and cognitive functioning) of the link between conscientiousness and longevity. ... We tested these mediators using a 10-year longitudinal sample [of 512 people], a subset of the long-running Health and Retirement Study of aging adults. Measures included an adjective-rating measure of conscientiousness, self-reported health conditions, and three measures of cognitive functioning (word recall, delayed recall, and vocabulary) included in the 1996 wave of the HRS study. ... Our results found that conscientiousness significantly predicted greater longevity, even in a model including the two proposed mediator variables, gender, age, and years of education. Moreover, cognitive functioning appears to partially mediate this relationship. ... This study replicates previous research showing that conscientious individuals tend to lead longer lives, and provides further insight into why this effect occurs."

MORE TRANSDIFFERENTIATION, SKIN CELLS TO NEURONS
Friday, May 27, 2011
http://www.fightaging.org/archives/2011/05/more-transdifferentiation-skin-cells-to-neurons.php
Transdifferentiation is the act of changing a cell directly from one type to another, without having to first go through the process of producing induced pluripotent stem cells and then differentiating them into the desired final product. This shows some promise as a yet more effective way of producing cells to order for research and therapies: "Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins ... The finding is significant because it bypasses the need to first create induced pluripotent stem cells, and may make it much easier to generate patient- or disease-specific neurons for study in a laboratory dish. It may also circumvent a recently reported potential problem with iPS cells, in which laboratory mice rejected genetically identical iPS cells - seemingly on the basis of the proteins used to render them pluripotent. The new research parallels that of the same Stanford group in 2010, which showed it was possible to change mouse skin cells directly into neurons with a similar combination of proteins. However, when done in human cells, the conversion of skin cells to neurons occurs less efficiently and more slowly. ... We are now much closer to being able to mimic brain or neurological diseases in the laboratory. We may perhaps even be able to one day use these cells for human therapies. ... The direct conversion of skin cells to neurons contrasts with similar research that first transforms skin cells to a pluripotent, or developmentally flexible, state and then coaxes them to become neurons or other specialized cells. ... The iPS cell approach is doable and has been shown to work. We need to keep working on both strategies. It's possible that the best approach may vary depending on the disease or the type of research being done."

DAMAGE, LIFESPAN, AND ITS MEASUREMENT IN NEMATODE WORMS
Thursday, May 26, 2011
http://www.fightaging.org/archives/2011/05/damage-lifespan-and-its-measurement-in-nematode-worms.php
This open access work looks like a solid way to measure accumulated biochemical damage in nematode worms, and link it to both its causes and its resulting effects on life span: "A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates. To unveil mechanisms that influence aging variability, we identified markers of remaining lifespan for Caenorhabditis elegans. In transgenic lines, we expressed fluorescent reporter constructs from promoters of C. elegans genes whose expression change with age. The expression levels of aging markers in individual worms from a young synchronous population correlated with their remaining lifespan. We identified eight aging markers, with the superoxide dismutase gene sod-3 expression being the best single predictor of remaining lifespan. Correlation with remaining lifespan became stronger if expression from two aging markers was monitored simultaneously, accounting for up to 49% of the variation in individual lifespan. ... Our results indicate that pathogenicity from Escherichia coli used as food is a major source of lifespan variability due to variable activation of the insulin-signaling pathway. ... E. coli, the common diet for worms, is mildly pathogenic whereas Bacillus subtilis is not pathogenic. Accordingly, worms fed B. subtilis live longer than worms grown on E. coli. ... The finding that the amount of sod-3 expression present in a middle-aged worm is correlated with its remaining lifespan indicates that events have occurred that affect its future aging trajectory. If so, feeding a worm either E. coli or B. subtilis should have greatest effect when it is young rather than when it is old. To test this, we fed worms one type of bacteria (E. coli or B. subtilis) when they were young and then shifted them to the other type of bacteria at day 8 of adulthood. Young worms fed E. coli had short lifespans, no matter what they ate when they were old. Conversely, young worms fed B. subtilis had long lifespans no matter what they ate when they were old. This result indicates that pathogenicity or some other factor associated with E. coli initiates changes in young worms that affect their time of death later on."

CALORIE RESTRICTION AND NITRIC OXIDE
Thursday, May 26, 2011
http://www.fightaging.org/archives/2011/05/calorie-restriction-and-nitric-oxide.php
An open access paper in which researchers delve into the mechanisms of longevity induced through calorie restriction in yeast: "Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. ... . Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan. ... CR-induced NO production may extend lifespan by increasing the stress response (mitohormesis). Our study may have uncovered potential novel components in the CR pathway and provided tools to analyze the interconnections between NO, mitochondrial respiration, CR, and longevity. Although the CR mimics identified in this study share similar NO levels, lifespan, and oxygen consumption phenotypes with CR, they may activate NO production and regulate mitochondrial respiration and lifespan via different mechanisms. It will be enlightening to examine these differences in future studies. Finally, we propose that CR likely confers its beneficial effects via a mitochondria-NO-mediated adaptive metabolic shift, which optimizes metabolism and at the same time improves cellular defense system against the oxidative stress that accumulates with age."

INTEREST IN RADICAL LIFE EXTENSION IN THE MAINSTREAM MEDIA
Wednesday, May 25, 2011
http://www.fightaging.org/archives/2011/05/interest-in-radical-life-extension-in-the-mainstream-media.php
As a sign of changing attitudes amongst run of the mill journalists whose first reaction is to mock everything that isn't widespread knowledge, this is encouraging: "Want to live to be a thousand years old? It's not far-fetched at all if you ask theoretician and geneticist Aubrey de Grey. He believes within the next 25 years there is a 50/50 chance we'll have the technologies to extend human life indefinitely. I learned of Aubrey and his ideas in 2005 and immediately pitched the story to NBC's Today Show. They were intrigued. With the help of correspondent Kerry Sanders and the London bureau, we went out and interviewed Aubrey in a pub in Cambridge. When we finished the story we sent it in to the show. It was promptly killed. Too out there for a mainstream audience. Plus it didn't help that Aubrey looked like Methuselah. Fast forward to 2011 and there Aubrey was in the news again. This time I pitched the story to HDNet's World Report. The program is always looking for stories that deal with interesting issues and are not widely told. This time correspondent Willem Marx met up with Aubrey in a pub in Cambridge and also went punting with him on the Thames River. For my part, I finally got to meet Aubrey at his SENS Foundation laboratory in Mountain View, California. He is tall and wiry and moves like someone with no time to lose. He lovingly strokes the beard which hangs almost to his waist. I asked him if his distinctive look helped or hurt him as he went out in the world trying to win over scientists and venture capitalists to support his work. He said it helped because people looked at him and saw a guy who is not materialistic in the least. It's very clear to them that he is not doing this to get rich. Through his SENS Foundation nonprofit, Aubrey and the scientists who work with him are creating an intersection between research on the biology of aging and regenerative medicine. By doing experiments with the building blocks of cells they hope to someday develop treatments that repair the damage caused by aging, and restore people to a state where they are biologically younger than they were when they started. In other words, people could live out their entire lives as healthy as young adults. Five years ago, the scientific community considered his ideas kind of kooky but now the research is catching up with his theories and Aubrey is gaining credibility. 'This is not science fiction anymore, this is science forseeable,' Aubrey proclaims."

IRON, COPPER, AND BRAIN DNA REPAIR
Wednesday, May 25, 2011
http://www.fightaging.org/archives/2011/05/iron-copper-and-brain-dna-repair.php
A novel view of the mechanisms of neurodegeneration: "o one knows the cause of most cases of Alzheimer's, Parkinson's and other neurodegenerative disorders. But researchers have found that certain factors are consistently associated with these debilitating conditions. One is DNA damage by reactive oxygen species, highly destructive molecules usually formed as a byproduct of cellular respiration. Another is the presence of excessive levels of copper and iron in regions of the brain associated with the particular disorder. ... A high level of copper or iron, they say, can function as a 'double whammy' in the brain by both helping generate large numbers of the DNA-attacking reactive oxygen species and interfering with the machinery of DNA repair that prevents the deleterious consequences of genome damage. ... We don't yet know enough about all the biochemical mechanisms involved, but we have found multiple toxic mechanisms linking elevated iron and copper levels in the brain and extensive DNA damage - pathological features associated with most neurodegenerative disorders. ... some people's tissues contain much larger quantities of iron or copper, which overwhelm the proteins that normally bind the metals and sequester them for safe storage. The result: so-called 'free' iron or copper ions, circulating in the blood and able to initiate chemical reactions that produce reactive oxygen species. Reactive oxygen species cause the majority of the brain cell DNA damage that we see in Alzheimer's and Parkinson's disease, as well as most other neurodegenerative disorders."

A REVIEW AND APPRAISAL OF THE ROLE OF DNA DAMAGE IN AGING
Tuesday, May 24, 2011
http://www.fightaging.org/archives/2011/05/a-review-and-appraisal-of-the-role-of-dna-damage-in-aging.php
A review paper: "Given the central role of DNA in life, and how ageing can be seen as the gradual and irreversible breakdown of living systems, the idea that damage to the DNA is the crucial cause of ageing remains a powerful one. DNA damage and mutations of different types clearly accumulate with age in mammalian tissues. Human progeroid syndromes resulting in what appears to be accelerated ageing have been linked to defects in DNA repair or processing, suggesting that elevated levels of DNA damage can accelerate physiological decline and the development of age-related diseases not limited to cancer. Higher DNA damage may trigger cellular signalling pathways, such as apoptosis, that result in a faster depletion of stem cells, which in turn contributes to accelerated ageing. Genetic manipulations of DNA repair pathways in mice further strengthen this view and also indicate that disruption of specific [repair pathways] is more strongly associated with premature ageing phenotypes. Delaying ageing in mice by decreasing levels of DNA damage, however, has not been achieved yet, perhaps due to the complexity inherent to DNA repair and DNA damage response pathways. Another open question is whether DNA repair optimization is involved in the evolution of species longevity, and we suggest that the way cells from different organisms respond to DNA damage may be crucial in species differences in ageing. Taken together, the data suggest a major role of DNA damage in the modulation of longevity, possibly through effects on cell dysfunction and loss, although understanding how to modify DNA damage repair and response systems to delay ageing remains a crucial challenge."

THE NEXT STEP IN THE STUDY OF LONGEVITY IN ASHKENAZI JEWS
Tuesday, May 24, 2011
http://www.fightaging.org/archives/2011/05/the-next-step-in-the-study-of-longevity-in-ashkenazi-jews.php
The topic of study moves from genes to stem cells: "Scientists at Cornell Medical College in New York are due to begin to study the stem cells of almost a dozen Ashkenazi Jews, who were a heavily persecuted group which originated from Russia. Experts believe that years of intermarriage - and the sharing of genetic traits - might have helped the group live for so long. In an attempt to find out how they live such long lives, research will be performed on the heart, lung, liver and other cells. .. The reason they live so long is not because they live healthy lives. Interbreeding can have a negative impact, but, in this case, some families had the opposite effect. They don't get cardiovascular disease, cancer, neurodegeneration or diabetes or very low rates. And we believe that one aspect to their resistance to disease has a stem-cell base. ... will extract stem cells from the elderly Jews' blood before transforming them into the cells of some vital organs ... The cells which have been engineered will then undergo stress tests, and then they will be assessed to see how they fared."

PRODUCING ASTROCYTES TO ORDER
Monday, May 23, 2011
http://www.fightaging.org/archives/2011/05/producing-astrocytes-to-order.php
Another cell type is added to the list of those that can be produced on demand in the laboratory: "Pity the lowly astrocyte, the most common cell in the human nervous system. Long considered to be little more than putty in the brain and spinal cord, the star-shaped astrocyte has found new respect among neuroscientists who have begun to recognize its many functions in the brain, not to mention its role in a range of disorders of the central nervous system. [Now] a group [reports] it has been able to direct embryonic and induced human stem cells to become astrocytes in the lab dish. The ability to make large, uniform batches of astrocytes [opens] a new avenue to more fully understanding the functional roles of the brain's most commonplace cell, as well as its involvement in a host of central nervous system disorders ranging from headaches to dementia. What's more, the ability to culture the cells gives researchers a powerful tool to devise new therapies and drugs for neurological disorders. ... Not a lot of attention has been paid to these cells because human astrocytes have been hard to get. But we can make billions or trillions of them from a single stem cell. Without the astrocyte, neurons can't function. Astrocytes wrap around nerve cells to protect them and keep them healthy. They participate in virtually every function or disorder of the brain. ... They could be used as screens to identify new drugs for treating diseases of the brain, they can be used to model disease in the lab dish and, in the more distant future, it may be possible to transplant the cells to treat a variety of neurological conditions, including brain trauma, Parkinson's disease and spinal cord injury. It is possible that astrocytes prepared for clinical use could be among the first cells transplanted to intervene in a neurological condition as the motor neurons affected by the fatal amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, are swathed in astrocytes."

SPURRING NEUROGENESIS IN THE LIVING BRAIN
Monday, May 23, 2011
http://www.fightaging.org/archives/2011/05/spurring-neurogenesis-in-the-living-brain.php
Researchers here demonstrate a method of adjusting the pace at which nerve cells in the brain are created, and suggest that it might work on other cell types in the body: "Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)-cyclinD1 complex in the adult mouse hippocampus cell autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4-cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells."

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I am looking for volunteers to undertake some light, spare-time research for Open Cures:

An open volunteer initiative that aims to speed the advent of biotechnologies that can slow down or repair aspects of the biological damage of aging and thus extend healthy human life. Our primary long-term goal is to bring together (a) promising but undeveloped biotechnologies of longevity and (b) the developers who can bring them to the clinic.

The Open Cures roadmap looks a way past the present foundational work (website, writing, organizational details, and so forth) and past the forthcoming efforts to build a repository of documentation for longevity-enhancing biotechnologies. Beyond all of that lies a process of building relationships with the medical tourism industry and developers outside the US. At present I have just as little an idea of the fine details of that process as you do - but discovery is half the challenge in building any initiative.

This is where research and volunteers come into the picture. There is a great deal of very useful information out there in various websites and publications that I would like to see assembled into one place - or at least the references to it all assembled in one place. This is light research work that any smart person with an internet connection can undertake, and it can take place in parallel to other foundational work for Open Cures - and be accomplished piecemeal by many different people. Many hands make light work.

Thus I am looking for volunteers to take on the assembly the following data, and other items that logically follow on from it, for as many different countries as make sense to look at. This may be a case of cleverly finding out that someone in the medical tourism industry has done much of this work already, but I think there's a little more to it than that. To my mind the eligible countries include much of the Asia-Pacific region, India, and a few others - but validating that list with real numbers is one of the tasks on the table.

The state of medical tourism

How many people travel to this country for medical procedures on a yearly basis, and how does that compare with historical data? Are there estimates for the market value of this medical tourism? Is there data broken down by types of procedures and institutions?

Noteworthy organizations and advocates in the field of medical tourism

Who is leading the charge in growing medical tourism to this country? Which organizations and advocates are prominent, both in the US and in the other country?

Conferences and trade shows

Where does the medical tourism industry focused on this country gather when they come together? Are there established conference series, either in the US or overseas? Are these general conferences, or focused on this particular country?

The state of investment into medical research

How much public and private investment into medical research takes place in this country? How does that break down by field of medicine?

Noteworthy developers and medical tourism destinations

Who are the leaders in offering new medical technologies for medical tourism in this country? What procedures do they specialize in? What is their background and how are they funded? For example, see Beike Biotech in China.

Existing international arrangements

Are there already examples of international cooperation between local developers in this country and developers or research groups in the US or Europe? For example, see Vescell/TheraVitae which offers stem cell treatments in Thailand, but is a Canadian and Israeli company. Countries and regions where there are existing arrangements will likely prove easier to nudge into producing new ones.

Legal environment

To what degree are developers in this country legally bound by various forms of intellectual property in the US? To what degree does that matter on a practical basis? Is there a lot of scofflaw development taking place, for example? The legal details are likely to be quite different for copyright, patents (and international patents), trademarks, and other distinct forms of intellectual property.

Other important matters

How does the country rank in safety for US tourism, local bureaucratic corruption, and items that will factor into its attractiveness as a destination?

One of the near term items on my to-do list for Open Cures is to set up a wiki to better allow people to incrementally contribute this sort of information. As data like this is assembled, it will be posted and made available as a resource to inform later decisions and relationship building exercises.

If you are interested in helping with this part of the Open Cures agenda, please sign up for the discussion group and let us know.

The conclusion of the researchers in this study is interesting, leaning as it does towards cognitive function rather than better implementation of health practices - though both general health and cognitive function are linked via mechanisms such as blood vessel health in the brain. Untangling the knots of many interrelated correlations in such complex things as human beings isn't easy: "Conscientious individuals tend to experience a number of health benefits, not the least of which being greater longevity. However, it remains an open question as to why this link with longevity occurs. The current study tested two possible mediators (physical health and cognitive functioning) of the link between conscientiousness and longevity. ... We tested these mediators using a 10-year longitudinal sample [of 512 people], a subset of the long-running Health and Retirement Study of aging adults. Measures included an adjective-rating measure of conscientiousness, self-reported health conditions, and three measures of cognitive functioning (word recall, delayed recall, and vocabulary) included in the 1996 wave of the HRS study. ... Our results found that conscientiousness significantly predicted greater longevity, even in a model including the two proposed mediator variables, gender, age, and years of education. Moreover, cognitive functioning appears to partially mediate this relationship. ... This study replicates previous research showing that conscientious individuals tend to lead longer lives, and provides further insight into why this effect occurs."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21604882

Transdifferentiation is the act of changing a cell directly from one type to another, without having to first go through the process of producing induced pluripotent stem cells and then differentiating them into the desired final product. This shows some promise as a yet more effective way of producing cells to order for research and therapies: "Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins ... The finding is significant because it bypasses the need to first create induced pluripotent stem cells, and may make it much easier to generate patient- or disease-specific neurons for study in a laboratory dish. It may also circumvent a recently reported potential problem with iPS cells, in which laboratory mice rejected genetically identical iPS cells - seemingly on the basis of the proteins used to render them pluripotent. The new research parallels that of the same Stanford group in 2010, which showed it was possible to change mouse skin cells directly into neurons with a similar combination of proteins. However, when done in human cells, the conversion of skin cells to neurons occurs less efficiently and more slowly. ... We are now much closer to being able to mimic brain or neurological diseases in the laboratory. We may perhaps even be able to one day use these cells for human therapies. ... The direct conversion of skin cells to neurons contrasts with similar research that first transforms skin cells to a pluripotent, or developmentally flexible, state and then coaxes them to become neurons or other specialized cells. ... The iPS cell approach is doable and has been shown to work. We need to keep working on both strategies. It's possible that the best approach may vary depending on the disease or the type of research being done."

Link: http://www.eurekalert.org/pub_releases/2011-05/sumc-ss052511.php

Senescent cells build up in our tissues with age. They have left the cell cycle, damaged and dysfunctional, fail to self-destruct through one of the many systems for cell suicide, and linger on to cause all sorts of problems for their neighbors. Tissue riddled with senescent cells is less effective, less resilient, and more prone to developing further damage.

One of the roles of the immune system is to clear out these problem cells, but the immune system itself progressively fails in all its tasks with age, a victim of its own issues. So the senescent cell population grows, promoted by increasing levels of damage caused by the other processes of aging, and the immune system fails to rein it in.

Here, researchers demonstrate one specific result of an increased population of senescent cells: an additional susceptibility to lung infection over and above the issues caused by an age-damaged immune system.

The researchers found that when it comes to aging and pneumonia, one bad apple can ruin the barrel. Lung cells that were supposed to die due to DNA damage - but didn't - were 5 to 15 times more susceptible to invasion by pneumonia-causing bacteria. These bad apples also increased the susceptibility of normal cells around them.

Both age and [pneumonia] are associated with senescent cells, which are unable to die due to dysregulated function. These cells have increased levels of proteins that disease-causing bacteria stick to and co-opt to invade the bloodstream. The cells also spew out molecules that increase inflammation, and make normal cells nearby do the same.

How will we deal with senescent cells with near future biotechnology? The likely answer is through the use of technologies pioneered in cancer research: precision cell-killing strategies that can locate and destroy very specific types of cell without harming any other cell types. These may use nanoparticles or they may involve training the immune system to attack senescent cells with vigor, but both paths have been demonstrated effective in the laboratory.

Sadly, as for so much of what might be done, next to no-one is actually working on adapting these developing technologies for use against senescent cells. That's one more thing to add to the long term to-do list for Open Cures and a strategy of promoting overseas development of new biotechnologies.

This open access work looks like a solid way to measure accumulated biochemical damage in nematode worms, and link it to both its causes and its resulting effects on life span: "A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates. To unveil mechanisms that influence aging variability, we identified markers of remaining lifespan for Caenorhabditis elegans. In transgenic lines, we expressed fluorescent reporter constructs from promoters of C. elegans genes whose expression change with age. The expression levels of aging markers in individual worms from a young synchronous population correlated with their remaining lifespan. We identified eight aging markers, with the superoxide dismutase gene sod-3 expression being the best single predictor of remaining lifespan. Correlation with remaining lifespan became stronger if expression from two aging markers was monitored simultaneously, accounting for up to 49% of the variation in individual lifespan. ... Our results indicate that pathogenicity from Escherichia coli used as food is a major source of lifespan variability due to variable activation of the insulin-signaling pathway. ... E. coli, the common diet for worms, is mildly pathogenic whereas Bacillus subtilis is not pathogenic. Accordingly, worms fed B. subtilis live longer than worms grown on E. coli. ... The finding that the amount of sod-3 expression present in a middle-aged worm is correlated with its remaining lifespan indicates that events have occurred that affect its future aging trajectory. If so, feeding a worm either E. coli or B. subtilis should have greatest effect when it is young rather than when it is old. To test this, we fed worms one type of bacteria (E. coli or B. subtilis) when they were young and then shifted them to the other type of bacteria at day 8 of adulthood. Young worms fed E. coli had short lifespans, no matter what they ate when they were old. Conversely, young worms fed B. subtilis had long lifespans no matter what they ate when they were old. This result indicates that pathogenicity or some other factor associated with E. coli initiates changes in young worms that affect their time of death later on."

Link: http://dx.doi.org/10.1371/journal.pgen.1002047

An open access paper in which researchers delve into the mechanisms of longevity induced through calorie restriction in yeast: "Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. ... . Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan. ... CR-induced NO production may extend lifespan by increasing the stress response (mitohormesis). Our study may have uncovered potential novel components in the CR pathway and provided tools to analyze the interconnections between NO, mitochondrial respiration, CR, and longevity. Although the CR mimics identified in this study share similar NO levels, lifespan, and oxygen consumption phenotypes with CR, they may activate NO production and regulate mitochondrial respiration and lifespan via different mechanisms. It will be enlightening to examine these differences in future studies. Finally, we propose that CR likely confers its beneficial effects via a mitochondria-NO-mediated adaptive metabolic shift, which optimizes metabolism and at the same time improves cellular defense system against the oxidative stress that accumulates with age."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092605/

There are three parallel tracks along which the future development of longevity science must progress, and we'll reach the end goal only as rapidly as the slowest of the three tracks moves.

1) Science and Biotechnology

The most obvious of the tracks is that the technologies of rejuvenation must be developed. We can see what the form that these technologies must take: damage repaired, waning cell populations renewed, waste byproducts broken down and removed, cancer thwarted. Initiatives like SENS can describe the needed procedures in great detail, at the level of cells and molecular machinery, as we truly are within a tantalizingly close reach of their creation.

But the biotechnologies of rejuvenation don't yet exist, and the many technology demonstrations of long-lived mice, flies, and worms in laboratories around the world are nothing but a warm-up for the main event. Even the amazing pace of progress in stem cell medicine and cancer research these days is just a toe across the starting line when it comes to true rejuvenation. A great deal of work lies ahead, for all that it is very clear just what that work must be.

We are truly fortunate in comparison to the previous generation of activists and scientists in being able to state the nature of a cure for aging. We can see exactly what it is that we need to accomplish - and so our job should be that much easier than theirs in many ways.

2) Clinical Development

Taking the output of the scientific method and turning it into reliable, affordable, widely available technology is no less a challenge than scientific progress. It is fraught with risk, and the stakes are much higher: the cost of developing new science is small in comparison to the costs of building an industry. Moving from one technology demonstration and a few patients to a technology used by hundreds of thousands of patients around the world is a massive undertaken in risk, development, innovation, and cutthroat competition.

Today, we see the impersonal engines of bureaucracy engaged in crushing this track to the future of longevity science. Practical medicine lags far behind practical science, and the costs of pushing through each new development program increase every year - thanks to organizations like the FDA, whose appointees have no incentive to do anything other than make it ever harder to bring new biotechnologies to the marketplace. In the case of longevity science, matters are yet worse than in other fields, as the FDA outright forbids commercial development of therapies for aging.

That the track of development and clinical translation of research is lagging so badly is what prompted me to the vision of the Vegas Group. That in turn led to the recent launch of Open Cures - an initiative to help speed commercial development of longevity science. There are plausible, cost-effective ways in which matters can be put right, making use of the existing institutions of medical tourism, overseas research and development, the internet, and the growing community of garage biotech and open biotech developers.

3) Persuasion

People strongly enough in favor of engineered human longevity to get up and do something about it, who have a fair layman's or better grasp of the science, and thus know enough to support research like SENS rather than fall for any of the nonsense put out by the "anti-aging" industry, probably number a few thousand. There are probably tens of thousands more of a similar mindset, but not are motivated enough to contribute materially beyond conversation and hope.

You can change the world with ten thousand people who think the same way as you do, that much is true, but it will be hard and it will take a long, long time. In the end, you'll only succeed by convincing hundreds of thousands more to contribute their support. It does't require all the world to agree with you. Half a percentage point of the world's population is hundreds of millions of people. Markets with hundreds of millions of customers are worth billions of dollars, even though they gain only a tiny, tiny fraction of the attention and expenditure of those people - and billions of dollars would be more than enough to fund the first emergence of true rejuvenation biotechnology.

The form of the track that lies ahead for advocacy is well known: at the highest level, all grand campaigns of persuasion are the same, and there are many successful examples to choose from in the field of patient advocacy. But it is a long way from where we are, a core group of thousands, to where we want to be - a core group of millions. Much remains to be accomplished.

As a sign of changing attitudes amongst run of the mill journalists whose first reaction is to mock everything that isn't widespread knowledge, this is encouraging: "Want to live to be a thousand years old? It's not far-fetched at all if you ask theoretician and geneticist Aubrey de Grey. He believes within the next 25 years there is a 50/50 chance we'll have the technologies to extend human life indefinitely. I learned of Aubrey and his ideas in 2005 and immediately pitched the story to NBC's Today Show. They were intrigued. With the help of correspondent Kerry Sanders and the London bureau, we went out and interviewed Aubrey in a pub in Cambridge. When we finished the story we sent it in to the show. It was promptly killed. Too out there for a mainstream audience. Plus it didn't help that Aubrey looked like Methuselah. Fast forward to 2011 and there Aubrey was in the news again. This time I pitched the story to HDNet's World Report. The program is always looking for stories that deal with interesting issues and are not widely told. This time correspondent Willem Marx met up with Aubrey in a pub in Cambridge and also went punting with him on the Thames River. For my part, I finally got to meet Aubrey at his SENS Foundation laboratory in Mountain View, California. He is tall and wiry and moves like someone with no time to lose. He lovingly strokes the beard which hangs almost to his waist. I asked him if his distinctive look helped or hurt him as he went out in the world trying to win over scientists and venture capitalists to support his work. He said it helped because people looked at him and saw a guy who is not materialistic in the least. It's very clear to them that he is not doing this to get rich. Through his SENS Foundation nonprofit, Aubrey and the scientists who work with him are creating an intersection between research on the biology of aging and regenerative medicine. By doing experiments with the building blocks of cells they hope to someday develop treatments that repair the damage caused by aging, and restore people to a state where they are biologically younger than they were when they started. In other words, people could live out their entire lives as healthy as young adults. Five years ago, the scientific community considered his ideas kind of kooky but now the research is catching up with his theories and Aubrey is gaining credibility. 'This is not science fiction anymore, this is science forseeable,' Aubrey proclaims."

Link: http://www.huffingtonpost.com/vicky-collins/longevity-research_b_858244.html

A novel view of the mechanisms of neurodegeneration: "o one knows the cause of most cases of Alzheimer's, Parkinson's and other neurodegenerative disorders. But researchers have found that certain factors are consistently associated with these debilitating conditions. One is DNA damage by reactive oxygen species, highly destructive molecules usually formed as a byproduct of cellular respiration. Another is the presence of excessive levels of copper and iron in regions of the brain associated with the particular disorder. ... A high level of copper or iron, they say, can function as a 'double whammy' in the brain by both helping generate large numbers of the DNA-attacking reactive oxygen species and interfering with the machinery of DNA repair that prevents the deleterious consequences of genome damage. ... We don't yet know enough about all the biochemical mechanisms involved, but we have found multiple toxic mechanisms linking elevated iron and copper levels in the brain and extensive DNA damage - pathological features associated with most neurodegenerative disorders. ... some people's tissues contain much larger quantities of iron or copper, which overwhelm the proteins that normally bind the metals and sequester them for safe storage. The result: so-called 'free' iron or copper ions, circulating in the blood and able to initiate chemical reactions that produce reactive oxygen species. Reactive oxygen species cause the majority of the brain cell DNA damage that we see in Alzheimer's and Parkinson's disease, as well as most other neurodegenerative disorders."

Link: http://www.eurekalert.org/pub_releases/2011-05/uotm-hic052011.php

I'd missed the emergence of the latest issue of Rejuvenation Research last month, which opens with this:

Possibly the biggest battle that I have had to fight over the past decade is to persuade people to take seriously the idea that it is time even to think about "reversing aging" while we remain so negligibly able even to slow aging down. The flaw in that logic is simple: it is that rejuvenation, i.e. the restoration of an organism's physiological state to how it was at an earlier age, will be achieved not by reversing the processes of aging but by repairing the accumulated damage that those processes create. To get back to where we came from, in other words, we do not need to retrace the route we took from there to here. Any route will do, and in this case there turns out to be a vastly more plausible route than the retracing one.

The debate over the the large-scale course of longevity science, focusing on either repair of aging (thus effectively reversing its effects) or slowing aging through re-engineering human metabolism, will determine how long we all live.

It is likely to be easier and less costly to produce rejuvenation therapies than to produce a reliable and significant slowing of aging. A rejuvenation therapy doesn't require a whole new metabolism to be engineered, tested, and understood - it requires that we revert clearly identified changes to return to a metabolic model that we know works, as it's used by a few billion young people already. Those rejuvenation therapies will be far more effective than slowing aging in terms of additional years gained, since you can keep coming back to use them again and again. They will also help the aged, who are not helped at all by a therapy that merely slows aging.

Whatever the course of research, the first resulting widespread therapies to significantly extend healthy human life are two or more decades away. Most of us will be old before the second generation of better and more reliable therapies emerges thereafter. Thus repair strategies for ongoing research must come to dominate the funding landscape over the next decade if we are to see meaningful progress in engineered human longevity within our lifetimes. Slowing aging will be of little use to us by the time it becomes available.

All of this means that this scientific debate is far too important for all of us to refrain from participation. We should all absolutely dive in and loudly offer our own opinions on the topic, and help the researchers and fundraisers focused on repair biotechnologies succeed in their aims: it is, after all, the future of all our lives on the line.

A review paper: "Given the central role of DNA in life, and how ageing can be seen as the gradual and irreversible breakdown of living systems, the idea that damage to the DNA is the crucial cause of ageing remains a powerful one. DNA damage and mutations of different types clearly accumulate with age in mammalian tissues. Human progeroid syndromes resulting in what appears to be accelerated ageing have been linked to defects in DNA repair or processing, suggesting that elevated levels of DNA damage can accelerate physiological decline and the development of age-related diseases not limited to cancer. Higher DNA damage may trigger cellular signalling pathways, such as apoptosis, that result in a faster depletion of stem cells, which in turn contributes to accelerated ageing. Genetic manipulations of DNA repair pathways in mice further strengthen this view and also indicate that disruption of specific [repair pathways] is more strongly associated with premature ageing phenotypes. Delaying ageing in mice by decreasing levels of DNA damage, however, has not been achieved yet, perhaps due to the complexity inherent to DNA repair and DNA damage response pathways. Another open question is whether DNA repair optimization is involved in the evolution of species longevity, and we suggest that the way cells from different organisms respond to DNA damage may be crucial in species differences in ageing. Taken together, the data suggest a major role of DNA damage in the modulation of longevity, possibly through effects on cell dysfunction and loss, although understanding how to modify DNA damage repair and response systems to delay ageing remains a crucial challenge."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21600302

The topic of study moves from genes to stem cells: "Scientists at Cornell Medical College in New York are due to begin to study the stem cells of almost a dozen Ashkenazi Jews, who were a heavily persecuted group which originated from Russia. Experts believe that years of intermarriage - and the sharing of genetic traits - might have helped the group live for so long. In an attempt to find out how they live such long lives, research will be performed on the heart, lung, liver and other cells. .. The reason they live so long is not because they live healthy lives. Interbreeding can have a negative impact, but, in this case, some families had the opposite effect. They don't get cardiovascular disease, cancer, neurodegeneration or diabetes or very low rates. And we believe that one aspect to their resistance to disease has a stem-cell base. ... will extract stem cells from the elderly Jews' blood before transforming them into the cells of some vital organs ... The cells which have been engineered will then undergo stress tests, and then they will be assessed to see how they fared."

Link: http://www.dailymail.co.uk/sciencetech/article-1390081/Scientists-study-stem-cells-New-York-Jews-East-European-roots-live-100.html

I'm pleased to announce that Open Cures has launched. This is the volunteer initiative sprung from discussion of the Vegas Group concept that has been taking place here for the past few months.

More than a dozen ways to extend life in mice have been demonstrated in laboratories

Yet the US Food and Drug Administration (FDA) forbids commercial therapies for aging
Thus the best biotechnologies for human longevity languish, undeveloped...

But this is a shrinking world, linked by the internet and medical tourism

Advanced, safe clinical development takes place in many countries

We can work around the FDA, and this is how it will be done »

Looking at the future of commercial medical development and rejuvenation biotechnology, it seems clear that something has to be done. The present state of affairs with respect to regulation of research and commercial development of biotechnologies in the US has forced to the sidelines any number of lines of research aimed at intervening in the aging process. These nascent biotechnologies, demonstrated on mice, cannot cost-effectively be commercially developed in the US - or cannot be developed at all, since the FDA will not approve treatments for aging. That fact is well known and has the predictable effect on the number of investors willing to pony up for the privilege of running into a brick wall.

Outside the US there are a number of developed nations which in which commercial medical development is less regulated. China for example - and US citizens of a certain age will no doubt feel sad that we can now point to modern day China as an example of comparative freedom in human endeavor. Not sad for the Chinese, but sad for us. Other nations in that part of the world are similarly more open than the US when it comes to commercial development of new medical technology: even India, despite its bureaucracy.

When we look to the future of commercial longevity-enhancing medical technologies - or indeed any cutting edge biotechnology - I think that we are looking at the process of building a bridge between the less restricted parts of the world and the output of the US research community. That bridge is forged of medical tourism, venture investment, and a flow of knowledge. Without it, little will be developed: there must be an outlet for new science to become new technology, and that outlet is being progressively narrowed in the US with each passing year.

We don't need to do anything about medical tourism or venture investment, as those fields are quite capable of looking after themselves and are growing rapidly, but where we are needed is to help build that flow of knowledge between regions. If we want to see real results in the clinic, we must establish a bridge between the potential longevity-enhancing technologies that have been demonstrated in the laboratory - but can never be fully realized in the US - and the developers half a world away who are free to translate the fruits of research into clinical application. This is a matter of documentation, of building relationships, and of pulling out the most interesting technology demonstrations into the light - as despite this shrinking world, it is still far from the case that researchers on opposite sides of the globe have a good view into what has and hasn't been accomplished.

There is a great that might be done to help this large-scale process along, especially now that we are moving in earnest into an age of open biotechnology. The impetus, as in software development, will be towards openly shared knowledge and designs, because the economic advantages are enormous. Accompanying this shift we will see an accelerating growth of the present community of lab collectives, semi-professional developers, and hobbyists in biotechnology. They already exist in the form of the , but that is just the earliest manifestation of what is to come, more akin to the Homebrew Computer Club of the 1970s that spawned computing hardware companies and the rampant growth that followed.

There is a wave coming, a vast growth in medical tourism and open development in biotechnology. We can help that wave form, and ride it to achieve our goals as it arrives.

All this considered, and the need for action very clear, I decided to launch Open Cures as a volunteer initiative, an open collaboration for everyone interested in accelerating the clinical development of the best longevity science demonstrated in laboratories. Our initial focus is on establishing the organizational basics and producing a good, open-access Creative Commons body of work that explains exactly how to carry out a range of biotechnologies shown to extend life or reverse specific biological aspects of aging in laboratory animals.

To that end, Open Cures patrons, starting with myself, are offering bounties on documentation outlines: if you are a life science graduate or post-graduate level student or an interested volunteer with a good knowledge of the field, I encourage you to drop by the Open Cures discussion group and introduce yourself.

Bounties are funded by Open Cures patrons as a way of speeding up work and attracting new volunteers to the initiative. At the present time, bounties focus on documentation needs: each award is made to the writer who first posts sufficiently good material to the Open Cures discussion group. Writers should expect some back and forth, questions asked, and friendly conversation when they do so. The bounty is then awarded when the writer releases their posted work under an open license; until that time, he or she retains copyright.

The primary purpose of awarding bounties is to discover good life science freelance writers, and who can therefore be paid a modest rate to produce further work on an ongoing, occasional basis. It is important to build lasting relationships with enthusiastic freelance writers who know the ins and outs of practical biotechnology - so when you submit good work that arrives too late to win a specific bounty, or is beaten out by another author, you are still a candidate for future writing projects.

Another cell type is added to the list of those that can be produced on demand in the laboratory: "Pity the lowly astrocyte, the most common cell in the human nervous system. Long considered to be little more than putty in the brain and spinal cord, the star-shaped astrocyte has found new respect among neuroscientists who have begun to recognize its many functions in the brain, not to mention its role in a range of disorders of the central nervous system. [Now] a group [reports] it has been able to direct embryonic and induced human stem cells to become astrocytes in the lab dish. The ability to make large, uniform batches of astrocytes [opens] a new avenue to more fully understanding the functional roles of the brain's most commonplace cell, as well as its involvement in a host of central nervous system disorders ranging from headaches to dementia. What's more, the ability to culture the cells gives researchers a powerful tool to devise new therapies and drugs for neurological disorders. ... Not a lot of attention has been paid to these cells because human astrocytes have been hard to get. But we can make billions or trillions of them from a single stem cell. Without the astrocyte, neurons can't function. Astrocytes wrap around nerve cells to protect them and keep them healthy. They participate in virtually every function or disorder of the brain. ... They could be used as screens to identify new drugs for treating diseases of the brain, they can be used to model disease in the lab dish and, in the more distant future, it may be possible to transplant the cells to treat a variety of neurological conditions, including brain trauma, Parkinson's disease and spinal cord injury. It is possible that astrocytes prepared for clinical use could be among the first cells transplanted to intervene in a neurological condition as the motor neurons affected by the fatal amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, are swathed in astrocytes."

Link: http://www.eurekalert.org/pub_releases/2011-05/uow-hbm051711.php

Researchers here demonstrate a method of adjusting the pace at which nerve cells in the brain are created, and suggest that it might work on other cell types in the body: "Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)-cyclinD1 complex in the adult mouse hippocampus cell autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4-cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells."

Link: http://jem.rupress.org/content/208/5/937

FIGHT AGING! NEWSLETTER
May 23rd 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- Introducing Open Cures
- The Most Mainstream of Longevity Science
- When Did We Become Suicidal, Negligent Barbarians?
- Discussion
- Latest Headlines from Fight Aging!

INTRODUCING OPEN CURES

The Vegas Group volunteer initiative is now renamed to Open Cures. The goals and background for this effort remain the same, and are explained at the Open Cures website, and in the discussion group:

http://www.opencures.org
http://groups.google.com/group/opencures

"We live in the midst of a revolution in biotechnology, a time of rapid and amazing progress; but this revolution is less than ideal when it comes to producing results in the clinic. Thanks to legal strictures placed upon medical development by government bodies - such as the Food and Drug Administration in the US - a range of biotechnologies with the potential to extend healthy life have been demonstrated in the laboratory but remain undeveloped for human use. ... To match the hectic, revolutionary change in the science of biotechnology, which leads to important new breakthroughs announced on a near-weekly basis, we would like to see sweeping changes in the way in which science demonstrated in the laboratory becomes medicine practiced in the clinic. The present system in the US and Europe is clearly broken."

Our present efforts focus on documenting the most promising longevity-enhancing biotechnologies in order to better make them useful and attractive for overseas developers, groups that are not subject to FDA restrictions. To this end, we will be offering bounties on some of the needed documentary material:

http://www.opencures.org/bounties

"Bounties are funded by Open Cures patrons as a way of speeding up work and attracting new volunteers to the initiative. At the present time, bounties focus on documentation needs: each award is made to the writer who first posts sufficiently good material to the Open Cures discussion group. Writers should expect some back and forth, questions asked, and friendly conversation when they do so. The bounty is then awarded when the writer releases their posted work under an open license; until that time, he or she retains copyright.

"The primary purpose of awarding bounties is to discover good life science freelance writers, and who can therefore be paid a modest rate to produce further work on an ongoing, occasional basis. It is important to build lasting relationships with enthusiastic freelance writers who know the ins and outs of practical biotechnology - so when you submit good work that arrives too late to win a specific bounty, or is beaten out by another author, you are still a candidate for future writing projects."

So if you know people who may be interested in the project, please point them to the Open Cures website. If you are interested in funding one of the upcoming bounties, either contact me or join the Open Cures discussion group and introduce yourself.

THE MOST MAINSTREAM OF LONGEVITY SCIENCE

Some thoughts spurred by an article surveying the dominant themes in present day work on interventions in the aging process:

http://www.fightaging.org/archives/2011/05/a-look-at-the-most-mainstream-of-longevity-science.php

"It is all a matter of great expense to achieve very modest goals in slowing aging, and that almost as a side-effect of the main aim, which is to catalog and understand the biochemistry of metabolism. ... This sort of research accounts for the vast majority of funding in longevity science, and if that remains true then we'll live just a little bit longer than our parents. Perhaps as much as ten years longer if the metabolic engineers pull an unexpected amazing advance from their hats within the next decade.

"From where I stand, that outcome would be a disaster - a missed opportunity with a cost of more than 50 million lives lost to aging and disease each and every year. If we reach 2040, after five decades of a scientific revolution in biotechnology, computing, and the ability to manipulate the fundamental components of life, and have not yet developed true rejuvenation biotechnology, capable of repairing the biochemical damage that causes aging ... well, we failed, and then some.

"Presently, that grand failure through a focus on trivial success is exactly where the scientific and medical development community is headed. Their timelines are for drugs and metabolic manipulations that give a small number of additional years of life to emerge by 2030 - decades of tinkering, decades of trials, and we're all old by the time that any modestly useful result emerges into general use. Yet the research community, the public, and the press are all absolutely focused on slowing aging, where they think about aging at all. Far too few people realize just how damaging to our prospects this state of affairs will be in the long run.

"This is why efforts like the SENS Foundation are so important: we need to see more groups building a platform, a body of work, and successfully making inroads into persuading the scientific community to work on repair of aging rather than just slowing it down. It won't take any longer to achieve meaningful success in repair-based research, given where things stand today, but the resulting difference to our lives and our health couldn't be greater."

WHEN DID WE BECOME SUICIDAL, NEGLIGENT BARBARIANS?

Possibly somewhere around 1940:

http://www.fightaging.org/archives/2011/05/when-did-we-become-suicidal-negligent-barbarians.php

"Our descendants will look back on us with some horror: an era of peoples who could have largely saved themselves from oblivion, but didn't. Suicidal, negligent barbarians they'll call us - and they'll be right. We have had the tools to preserve the brains of the dead for the long haul for quite some time now, and preserve them well enough that the fine structures storing the data of the mind remain intact. Death is death, but oblivion only occurs when the present detailed arrangement of matter in your brain is destroyed. For so long as that data is preserved, there is the chance that future technology and circumstances will lead to a restoration of life, such as through the use of advanced nanotechnology and charitable groups dedicated to returning the preserved to active life once more.

"Sympathy is appropriate for those with high ideals and no possibility of ever achieving them - simply born too soon. But what of those who could achieve but turn aside and shirk the task? That would be us. I'd say we and our immediate forebears became suicidal, negligent barbarians about ten years after it became possible to build an industry to preserve brains, with a cost at scale that was affordable to the masses - on a par with funerals, for example.

"For preservation methods along the lines of plastination, that point probably came and went somewhere in the 1930s or early 1940s, with the growth of the chemical industry into a true giant. The 1930s also saw the development of the first electron microscopes, and life scientists of the time arguably possessed enough knowledge of the cell to make educated guesses about which forms of chemical or low-temperature preservation would retain the data of the mind.

"Here we stand, three generations removed, a thousand distinct human cultures in which there is little to show that we desire anything other than oblivion or self-delusion when it comes to our lives. Judging by actions rather than words, people who greatly desire both lasting life and health are a minority indeed. And with each passing year, another fifty million lives vanish into the maw to be destroyed utterly."

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

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LATEST HEADLINES FROM FIGHT AGING!

ON CRYONICS AND DEFINITIONS OF DEATH
Friday, May 20, 2011
http://www.fightaging.org/archives/2011/05/on-cryonics-and-definitions-of-death.php
From Depressed Metabolism: "It has been said that if you want to persuade someone, you need to find common ground. But one of the defining characteristics of cryonics is that proponents and opponents cannot even seem to agree on the criteria that should be employed in discussing cryonics. The cryonics skeptic will argue that the idea of cryonics is dead on arrival because cryonics patients are dead. The response of the cryonics advocate is that death is not a state but a process and there is good reason to believe that a person who is considered dead today may not be considered dead by a future physician. In essence, the cryonics advocate is arguing that his skeptical opponent would agree with him if he would just embrace his conception of death ... Cryonicists have named their favorite conception of death 'information-theoretic death.' In a nutshell, a person is said to be dead in the information-theoretic sense of the word if no future technologies are capable of inferring the original state of the brain that encodes the person's memories and identity. There are a lot of good things to be said about substituting this more rigorous criterion of death for our current definitions of death. However, in this brief paper I will argue that our best response does not necessarily need to depend on skeptics embracing such alternative definitions of death and that we may be able to argue that opponents of cryonics should support legal protection for cryonics patients or risk contradicting conventional definitions of death."

COMMENTARY ON MEASURING TELOMERES
Friday, May 20, 2011
http://www.fightaging.org/archives/2011/05/commentary-on-measuring-telomeres.php
With the advent of commercial telomere length measurement services, there's been a lot of unscientific hype in the media of late about tests that will show how long you're going to live. Some more sensible commentary here from FuturePundit: "the test can not precisely predict your year of death. Too many factors (accidents, suicide, and murder aside) influence your date of death. Take cancer for example. There's a lot of randomness involved in determining when we'll get cancer. The accumulation of damage in cells can make them turn cancerous. But just when the right set of genetic mutations or other cancer-promoting damage will occur in some cell in one's body is as hard to predict as when someone will win a lottery. Many things have to line up just right all in the same cell to make it cancerous. Every day is basically another throw of the dice. Will a bunch of mutations all line up to send a cell of yours into dangerous mad replication and growth? Better longevity tests seem useful for retirement planning. Should you save enough money to support yourself to age 95? Or expect to die by your late 60s? A telomere test could help you decide difficult questions about your savings rate and career choices. Do you need to work past age 70 to save enough money to avoid going broke in your 80s and avoid poverty in your 90s? A better sense of the odds would help. Of course, before we hit our biological shelf life expiration date some of us just might live long enough to still be around when rejuvenation therapies become available. Injections of youthful stem cells with long telomeres could replace older tired cells with short telomeres. This would be great for the immune system, for example, because a youthful immune system will do a better job of fighting cancer. Also, youthful cells for the cardiovascular system could cut the risk of heart disease, stroke, and other killers." The high level point being that unless you are old already the future of your life span has less to do with your telomeres and more do to with progress in medical science.

ALCOR VIDEO LIBRARY UPDATED
Thursday, May 19, 2011
http://www.fightaging.org/archives/2011/05/alcor-video-library-updated.php
From Alcor News: "The Alcor Video Library has recently added new material. It now includes a short Video Tour of Alcor Facility and five complete presentations from the 2006 Alcor Conference. The video quality has also been significantly upgraded. ... The Limitless Future (28-minutes). Alcor documentary video (2005). Discover how leading-edge science at the Alcor Life Extension Foundation is getting closer to making the dream of a vastly extended lifespan come true and how our notion of "death" is shifting. Includes interviews with world-renowned scientists including Dr. Aubrey de Grey, [explaining] how life can be cryopreserved on the verge of death and then revitalized, giving us a second chance at a long and productive life, and Dr. Ralph Merkle, Distinguished Professor of Computing at Georgia Tech, exploring how molecular-sized machines will be able to repair damage to your body from aging or the devastating effects of cancer and other illnesses, including frostbite." You might also take a look at some of the other videos linked in the post, such as a presentation on the economics of longevity: "In this talk, Dr. Friedman shares his insights into the many potential consequences of an extended lifespan. He asks provocative questions about the future of the family unit, a typical career path, and the economic outlook for society as a whole."

MORE HEART PATCHING
Thursday, May 19, 2011
http://www.fightaging.org/archives/2011/05/more-heart-patching.php
Patching a damaged heart is on the agenda again, with nanoscale-featured scaffold material this time: "When you suffer a heart attack, a part of your heart dies. Nerve cells in the heart's wall and a special class of cells that spontaneously expand and contract - keeping the heart beating in perfect synchronicity - are lost forever. [At present] surgeons can't repair the affected area [but the] best approach would be to figure out how to resuscitate [it] ... scientists turned to nanotechnology. In a lab, they built a scaffold-looking structure consisting of carbon nanofibers and a government-approved polymer. Tests showed the synthetic nanopatch regenerated natural heart tissue cells ­- called cardiomyocytes - as well as neurons. In short, the tests showed that a dead region of the heart can be brought back to life. ... the engineers employed carbon nanofibers, helical-shaped tubes with diameters between 60 and 200 nanometers. The carbon nanofibers work well because they are excellent conductors of electrons, performing the kind of electrical connections the heart relies upon for keeping a steady beat. ... In tests with the 200-nanometer-diameter carbon nanofibers seeded with cardiomyocytes, five times as many heart-tissue cells colonized the surface after four hours than with a control sample consisting of the polymer only. ... The scaffold works because it is elastic and durable, and can thus expand and contract much like heart tissue. ... It's because of these properties and the carbon nanofibers that cardiomyocytes and neurons congregate on the scaffold and spawn new cells, in effect regenerating the area."

TOWARDS TREATMENTS FOR AGE-RELATED MUSCLE LOSS
Wednesday, May 18, 2011
http://www.fightaging.org/archives/2011/05/towards-treatments-for-age-related-muscle-loss.php
Stem cell therapies are one theoretical path towards therapies for sarcopenia, the loss of muscle mass and strength with age. Here, researchers have discovered "the mechanism that causes stem cells in the embryo to differentiate into specialised cells that form the skeletal muscles of animals' bodies. ... The field has the potential to revolutionise medicine by delivering therapies to regenerate tissue damaged by disease or injury. Differentiation happens soon after fertilisation, when embryonic cells are dividing rapidly and migrating as the animal's body takes shape. ... The scientists investigated the effect of a known signalling pathway called NOTCH on muscle differentiation. They found that differentiation of stem cells to muscle was initiated when NOTCH signalling proteins touched some of the cells. These proteins were carried by passing cells migrating from a different tissue - the neural crest - the progenitor tissue of sensory nerve cells. Muscle formation in the target stem cells occurred only when the NOTCH pathway was triggered briefly by the migrating neural crest cells. ... This kiss-and-run activation of a pathway is a completely novel mechanism of stem cell specification which explains why only some stem cells adopt a muscle cell fate. ... the team would now focus on unravelling the mechanisms of embryonic muscle cell differentiation at the molecular level as a necessary step to regulating regeneration of the muscles in human patients."

SENS FOUNDATION SEEKS ACADEMIC COORDINATOR
Wednesday, May 18, 2011
http://www.fightaging.org/archives/2011/05/sens-foundation-seeks-academic-coordinator.php
From the SENS Foundation: "SENS Foundation is a 501c3 non-profit which works to develop, promote and ensure widespread access to rejuvenation biotechnologies which comprehensively address the disabilities and diseases of aging. The Foundation combines significant direct research efforts with education, affiliation and outreach programs. The SENS Foundation Academic Initiative (AI) is the nexus of its educational activities, which includes student mentoring, small but growing grants and scholarship programs, and coursework development. SENS Foundation is seeking a staff member to be Academic Coordinator. The Academic Coordinator will oversee the Academic Initiative and be responsible for designing, implementing and expanding projects and programs that support the aims of SENS Foundation. Additional responsibilities will include managing AI volunteer staff and students; maintaining active communication with SENS Foundation management, the Foundation Research Center, and AI volunteers; and establishing and maintaining reporting measures to document AI operations. The AC will report to the CEO, and work closely with the CSO, Vice President, and Director of Research Operations. Major projects already in development include the creation of online undergraduate courses in longevity science, development of a comprehensive training program, continuance and expansion of the scholarship and mentoring program, and implementation of a comprehensive marketing strategy to expand and promote the Academic Initiative."

STEM CELLS REVERSE PARKINSON'S IN RATS
Tuesday, May 17, 2011
http://www.fightaging.org/archives/2011/05/stem-cells-reverse-parkinsons-in-rats.php
Promising news: "A team of researchers [has] now compared the ability of cells derived from different types of human stem cell to reverse disease in a rat model of Parkinson disease and identified a stem cell population that they believe could be clinically relevant. ... Parkinson disease results from the progressive loss of a specific subpopulation of nerve cells. Current treatments provide only relief from the symptoms of the disease and cannot reverse the nerve cell loss. Stem cells are considered by many to be promising candidate sources of cells to reverse nerve cell loss in individuals with Parkinson disease through their ability to regenerate and repair diseased tissues. ... There are two types of stem cell considered in this context: embryonic stem (ES) cells, which are derived from early embryos; and induced pluripotent stem (iPS) cells, which are derived by reprogramming cells of the body such that they have the ability to generate any cell type. In turn, cells of the body can be reprogrammed to become iPS cells in one of two ways: the reprogramming proteins can be transferred directly into the cells (protein-based iPS cells) or viruses can be used to deliver to the cells the genetic information necessary for producing the reprogramming proteins (virus-based iPS cell). [Researchers] found several problems with cells derived from virus-based human iPS cells that precluded their use in the Parkinson disease model but found that nerve cells derived from protein-based human iPS cells reversed disease when transplanted into the brain of rats modeling Parkinson disease. They therefore conclude that protein-based human iPS cells could be used in the treatment of individuals with Parkinson disease."

MORE RETINAL REGENERATION
Tuesday, May 17, 2011
http://www.fightaging.org/archives/2011/05/more-retinal-regeneration.php
From EurekAlert!: researchers "are the first to regenerate large areas of damaged retinas and improve visual function using IPS cells (induced pluripotent stem cells) derived from skin. ... While other researchers have been successful in converting skin cells into induced pluripotent stem cells (iPSCs) and subsequently into retinal neurons, we believe that this is the first time that this degree of retinal reconstruction and restoration of visual function has been detected ... Today, diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are the leading causes of incurable blindness in the western world. In these diseases, retinal cells, also known as photoreceptors, begin to die and with them the eye's ability to capture light and transmit this information to the brain. Once destroyed, retinal cells, like other cells of the central nervous system have limited capacity for endogenous regeneration. ... Stem cell regeneration of this precious tissue is our best hope for treating and someday curing these disorders. ... [Researchers] harvested skin cells from the tails of red fluorescent mice. They used red mice, because the red tissue would be easy to track when transplanted in the eyes of non-fluorescent diseased mice. ... the group generated red fluorescent IPSCs, and, with additional chemical coaxing, precursors of retinal cells. ... Within 33 days the cells were ready to be transplanted and were introduced into the eyes of a mouse model of retina degenerative disease. ... Within four to six weeks, the researchers observed that the transplanted 'red' cells had taken up residence in the appropriate retinal area (photoreceptor layer) of the eye and had begun to integrate and assemble into healthily looking retinal tissue."

N-GLYCAN PROFILES AND INHERITED LONGEVITY
Monday, May 16, 2011
http://www.fightaging.org/archives/2011/05/n-glycan-profiles-and-inherited-longevity.php
Some people can live moderately longer than others due to differences in their genes that enhance the ability of a good lifestyle to extend life, or blunt the tendency for a bad lifestyle to shorten life. In this age of biotechnology it is only a matter of time before all the biochemical differences between naturally longer-lived and shorter-lived human lineages are uncovered: "The development of medical interventions for the preservation of disease-free longevity would be facilitated by markers that predict healthy aging. Altered protein N-glycosylation patterns have been found with increasing age and several disease states. Here we investigate whether glycans derived from the total glycoprotein pool in plasma mark familial longevity and distinguish healthy from unhealthy aging. Total plasma N-glycan profiles of 2396 middle aged participants in the Leiden Longevity Study (LLS) were obtained ... After normalization and batch correction, several regression strategies were applied to evaluate associations between glycan patterns, familial longevity, and healthy aging. Two N-glycan features (LC-7 and LC-8) were identified to be more abundant in plasma of the offspring of long-lived individuals as compared to controls. ... Furthermore, a decrease in levels of LC-8 was associated with the occurrence of myocardial infarction, indicating that plasma glycosylation patterns do not only mark familial longevity but may also reflect healthy aging. In conclusion, we describe two glycan features, of which increased levels mark familial longevity and decreased levels of one of these features mark the presence of cardiovascular disease."

ANOTHER PAPER ON BRANCHED-CHAIN AMINO ACIDS
Monday, May 16, 2011
http://www.fightaging.org/archives/2011/05/another-paper-on-branched-chain-amino-acids.php
Researchers continue to investigate the effects of branched-chain amino acids (BCAA) on life span in laboratory animals: "Identification of strategies mimicking key [calorie restriction (CR)] mechanisms - increased mitochondrial respiration and reduced production of oxygen radicals - is a hot topic in gerontology. Dietary supplementation with essential and/or branched chain amino acids (BCAAs) exerts a variety of beneficial effects in experimental animals and humans and has been recently demonstrated to support cardiac and skeletal muscle mitochondrial biogenesis, prevent oxidative damage, and enhance physical endurance in middle-aged mice, resulting in prolonged survival. ... A body of recent evidence suggest that amino acids, and in particular BCAAs, behave as evolutionary conserved modulators of lifespan of different organisms ... [Like exercise, BCAA supplementation] does not affect maximum lifespan, but increases the median lifespan, an indicator that specific diseases have been prevented. ... A broad range of questions await answers. The first point to be clarified is the role that specific amino acid signatures can play, directly or indirectly, in the CR effects on healthspan. ... there is need to investigate which amino acid (or specific amino acid combination) is required for the beneficial effects seen in mammals. Not last in importance, large, randomized clinical trials are necessary to assess the safety and efficacy of BCAA/amino acid supplementation for the prevention and treatment of the disabling consequences of energy depletion in the elderly."

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A Science News article here looks at the most well known and best funded research into slowing aging. It is all a matter of great expense to achieve very modest goals in slowing aging, and that almost as a side-effect of the main aim, which is to catalog and understand the biochemistry of metabolism.

A drug that postpones aging could also have profound health benefits, since most common diseases (such as cancer, heart disease and dementia) accompany old age. "That's what's driving us," says Donald Ingram, head of the nutritional neuroscience and aging laboratory at Pennington Biomedical Research Center in Baton Rouge, La. "We would like to see some kind of a product that would promote healthy aging."

So far, scientists have singled out a handful of synthetic and natural compounds that appear to trigger the same biochemical mechanisms that kick in when cells are partially starved of nutrients, part of a coping mechanism that protects against stress.

This sort of research accounts for the vast majority of funding in longevity science, and if that remains true then we'll live just a little bit longer than our parents. Perhaps as much as ten years longer if the metabolic engineers pull an unexpected amazing advance from their hats within the next decade.

From where I stand, that outcome would be a disaster - a missed opportunity with a cost of more than 50 million lives lost to aging and disease each and every year. If we reach 2040, after five decades of a scientific revolution in biotechnology, computing, and the ability to manipulate the fundamental components of life, and have not yet developed true rejuvenation biotechnology, capable of repairing the biochemical damage that causes aging ... well, we failed, and then some.

Presently, that grand failure through a focus on trivial success is exactly where the scientific and medical development community is headed. Their timelines are for drugs and metabolic manipulations that give a small number of additional years of life to emerge by 2030 - decades of tinkering, decades of trials, and we're all old by the time that any modestly useful result emerges into general use. Yet the research community, the public, and the press are all absolutely focused on slowing aging, where they think about aging at all. Far too few people realize just how damaging to our prospects this state of affairs will be in the long run.

This is why efforts like the SENS Foundation are so important: we need to see more groups building a platform, a body of work, and successfully making inroads into persuading the scientific community to work on repair of aging rather than just slowing it down. It won't take any longer to achieve meaningful success in repair-based research, given where things stand today, but the resulting difference to our lives and our health couldn't be greater.

From Depressed Metabolism: "It has been said that if you want to persuade someone, you need to find common ground. But one of the defining characteristics of cryonics is that proponents and opponents cannot even seem to agree on the criteria that should be employed in discussing cryonics. The cryonics skeptic will argue that the idea of cryonics is dead on arrival because cryonics patients are dead. The response of the cryonics advocate is that death is not a state but a process and there is good reason to believe that a person who is considered dead today may not be considered dead by a future physician. In essence, the cryonics advocate is arguing that his skeptical opponent would agree with him if he would just embrace his conception of death ... Cryonicists have named their favorite conception of death 'information-theoretic death.' In a nutshell, a person is said to be dead in the information-theoretic sense of the word if no future technologies are capable of inferring the original state of the brain that encodes the person's memories and identity. There are a lot of good things to be said about substituting this more rigorous criterion of death for our current definitions of death. However, in this brief paper I will argue that our best response does not necessarily need to depend on skeptics embracing such alternative definitions of death and that we may be able to argue that opponents of cryonics should support legal protection for cryonics patients or risk contradicting conventional definitions of death."

Link: http://www.depressedmetabolism.com/2011/05/16/neural-cryobiology-and-the-legal-recognition-of-cryonics/

With the advent of commercial telomere length measurement services, there's been a lot of unscientific hype in the media of late about tests that will show how long you're going to live. Some more sensible commentary here from FuturePundit: "the test can not precisely predict your year of death. Too many factors (accidents, suicide, and murder aside) influence your date of death. Take cancer for example. There's a lot of randomness involved in determining when we'll get cancer. The accumulation of damage in cells can make them turn cancerous. But just when the right set of genetic mutations or other cancer-promoting damage will occur in some cell in one's body is as hard to predict as when someone will win a lottery. Many things have to line up just right all in the same cell to make it cancerous. Every day is basically another throw of the dice. Will a bunch of mutations all line up to send a cell of yours into dangerous mad replication and growth? Better longevity tests seem useful for retirement planning. Should you save enough money to support yourself to age 95? Or expect to die by your late 60s? A telomere test could help you decide difficult questions about your savings rate and career choices. Do you need to work past age 70 to save enough money to avoid going broke in your 80s and avoid poverty in your 90s? A better sense of the odds would help. Of course, before we hit our biological shelf life expiration date some of us just might live long enough to still be around when rejuvenation therapies become available. Injections of youthful stem cells with long telomeres could replace older tired cells with short telomeres. This would be great for the immune system, for example, because a youthful immune system will do a better job of fighting cancer. Also, youthful cells for the cardiovascular system could cut the risk of heart disease, stroke, and other killers." The high level point being that unless you are old already the future of your life span has less to do with your telomeres and more do to with progress in medical science.

Link: http://www.futurepundit.com/archives/008089.html

One of the most interesting things to emerge from a rigorous comparison of the biology of aging between species is the role of cell membrane composition, as outlined in the membrane pacemaker hypothesis.

The membrane pacemaker hypothesis predicts that long-living species will have more peroxidation-resistant membrane lipids than shorter living species.

Resistance to oxidative damage is of particular importance in mitochondria, cellular power plants that progressive damage themselves with the reactive oxygen species they produce as a byproduct of their operation - and that gives rise to a chain of further biochemical damage that spreads throughout the body, growing ever more harmful as you age. Less damage to the mitochondria should mean slower aging, and thus more resistant mitochondrial membranes should also mean slower aging.

The evidence for this view is good, and continues to accumulate. See, for example, investigations of the biology of naked mole rats and other long-lived species with unusual biochemistries. As this recent review paper notes:

The relationship between membrane fatty acid composition and longevity is discussed for (1) mammals of different body size, (2) birds of different body size, (3) mammals and birds that are exceptionally long-living for their size, (4) strains of mice that vary in longevity, (5) calorie-restriction extension of longevity in rodents, (6) differences in longevity between queen and worker honeybees, and (7) variation in longevity among humans. Most of these comparisons support an important role for membrane fatty acid composition in the determination of longevity. It is apparent that membrane composition is regulated for each species. ... The exceptional longevity of Homo sapiens combined with the limited knowledge of the fatty acid composition of human tissues support the potential importance of mitochondrial membranes in determination of longevity.

This, I think, is one of the best illustrations for the merits of comparative studies of the biology of aging. Absent data from a range of different species, it seems unlikely that the membrane pacemaker hypothesis would have gathered as much interest in the community. Here's a related commentary:

Comparative biology plays several roles in our understanding of the virtually ubiquitous phenomenon of aging in animals. First, it provides a critical evaluation of broad hypotheses concerning the evolutionary forces underlying the modulation of aging rate. Second, it suggests mechanistic hypotheses about processes of aging. Third, it illuminates particularly informative species because of their exceptionally slow or rapid aging rates to be interrogated about potentially novel mechanisms of aging. Although comparative biology has played a significant role in research on aging for more than a century, the new comparative biology of aging is poised to dwarf those earlier contributions

For my part, focused as I am on the biotechnologies of human longevity, I see the most important aspect of this discussion being that it draws more attention to mitochondria, mitochondrial structure, and the prospects for mitochondrial repair. Clearly it is the case that human mitochondria serve well for the first few decades of life, and it is only later that the level of mitochondrial damage becomes large enough for degenerative aging to become materially apparent.

From Alcor News: "The Alcor Video Library has recently added new material. It now includes a short Video Tour of Alcor Facility and five complete presentations from the 2006 Alcor Conference. The video quality has also been significantly upgraded. ... The Limitless Future (28-minutes). Alcor documentary video (2005). Discover how leading-edge science at the Alcor Life Extension Foundation is getting closer to making the dream of a vastly extended lifespan come true and how our notion of "death" is shifting. Includes interviews with world-renowned scientists including Dr. Aubrey de Grey, [explaining] how life can be cryopreserved on the verge of death and then revitalized, giving us a second chance at a long and productive life, and Dr. Ralph Merkle, Distinguished Professor of Computing at Georgia Tech, exploring how molecular-sized machines will be able to repair damage to your body from aging or the devastating effects of cancer and other illnesses, including frostbite." You might also take a look at some of the other videos linked in the post, such as a presentation on the economics of longevity: "In this talk, Dr. Friedman shares his insights into the many potential consequences of an extended lifespan. He asks provocative questions about the future of the family unit, a typical career path, and the economic outlook for society as a whole."

Link: http://www.alcor.org/blog/?p=2040

Patching a damaged heart is on the agenda again, with nanoscale-featured scaffold material this time: "When you suffer a heart attack, a part of your heart dies. Nerve cells in the heart's wall and a special class of cells that spontaneously expand and contract - keeping the heart beating in perfect synchronicity - are lost forever. [At present] surgeons can't repair the affected area [but the] best approach would be to figure out how to resuscitate [it] ... scientists turned to nanotechnology. In a lab, they built a scaffold-looking structure consisting of carbon nanofibers and a government-approved polymer. Tests showed the synthetic nanopatch regenerated natural heart tissue cells ­- called cardiomyocytes - as well as neurons. In short, the tests showed that a dead region of the heart can be brought back to life. ... the engineers employed carbon nanofibers, helical-shaped tubes with diameters between 60 and 200 nanometers. The carbon nanofibers work well because they are excellent conductors of electrons, performing the kind of electrical connections the heart relies upon for keeping a steady beat. ... In tests with the 200-nanometer-diameter carbon nanofibers seeded with cardiomyocytes, five times as many heart-tissue cells colonized the surface after four hours than with a control sample consisting of the polymer only. ... The scaffold works because it is elastic and durable, and can thus expand and contract much like heart tissue. ... It's because of these properties and the carbon nanofibers that cardiomyocytes and neurons congregate on the scaffold and spawn new cells, in effect regenerating the area."

Link: http://www.eurekalert.org/pub_releases/2011-05/bu-rcn051711.php

I was reminded today that the Foresight Institute is holding an event next month, on June 25th-26th in the Bay Area, California. Some of the speakers and topics are relevant to those of us interested in longevity science, such as William Andregg of Halcyon Molecular, a fellow who has no problems in speaking his mind when it comes to achieving radical extension of the healthy human life span. The conference reminder came with a $50 discount to the conference registration price for Fight Aging! readers - just enter FIGHTAGING when registering.

Join friends old and new this summer at Google's Mountain View headquarters in Silicon Valley as we explore the future of nanotech with a rockstar lineup of nanotech experts and entrepreneurs.

Want to understand the science behind the dream? Find out why Sir Fraser Stoddart's successful development of molecular switches and motor-molecules merited him a knighthood. Talk molecular robotics with Ari Requicha, or molecular computation with quantum theorist William A Goddard, III. See single atoms with microscopist Andrew Bleloch, hear how Feynman Prize-winner Christian Schafmeister builds macromolecules, and find out how rising star Matt Francis is shaking up the world of synthetic biology.

Want innovative entrepreneurial applications? Hear word from the nanostartup trenches with Halcyon Molecular founder William Andregg and "Mad Scientist" One-Nano CEO Rob Meagley. Find out about new nanotech initiatives from IBM's decade-long, worldwide Director of Physical Sciences, Thomas Theis. Learn the practical impact of nanotech innovation in a forecast from futurist expert Paul Saffo, or the problems of financing them with Founders Fund partner and Paypal founder Luke Nosek.

For some pointers as to why progress in the field of nanotechnology is important for longevity science, you might look back in the Fight Aging! archives. Bear in mind that, as a bottom line, everything that goes wrong as we age is caused by atoms and molecules that are out of place. Progress in biotechnology is very much a matter of learning how to - as precisely as possible - identify and manipulate certain problematic atoms and molecules:

• Dreams of Molecular Nanotechnology
• The Desires Made Real By a Mature Molecular Manufacturing Technology Base

Systems that can identify, manage and place trillions of molecules accurately are not a pipe dream; after all, we are already surrounded by examples. You, for example, are just such a system, albeit somewhat slow at self-assembly to full size. There's nothing in the laws of physics that jumps out and says we can't do this. It's just a matter of time.

If you have the technology base to build a nanoforge to assemble a brick, then you also have the technology base capable of simultaneously assembling and controlling a hundred million medical nanorobots of arbitrary design and programming. Or an artifical lung better than the real thing, or replacements for immune cells that never get old or worn. You get the idea. A brick is just as complex as any portion of the human body if you have to build the thing molecule by molecule; more fault-tolerant, but just as complex.

Stem cell therapies are one theoretical path towards therapies for sarcopenia, the loss of muscle mass and strength with age. Here, researchers have discovered "the mechanism that causes stem cells in the embryo to differentiate into specialised cells that form the skeletal muscles of animals' bodies. ... The field has the potential to revolutionise medicine by delivering therapies to regenerate tissue damaged by disease or injury. Differentiation happens soon after fertilisation, when embryonic cells are dividing rapidly and migrating as the animal's body takes shape. ... The scientists investigated the effect of a known signalling pathway called NOTCH on muscle differentiation. They found that differentiation of stem cells to muscle was initiated when NOTCH signalling proteins touched some of the cells. These proteins were carried by passing cells migrating from a different tissue - the neural crest - the progenitor tissue of sensory nerve cells. Muscle formation in the target stem cells occurred only when the NOTCH pathway was triggered briefly by the migrating neural crest cells. ... This kiss-and-run activation of a pathway is a completely novel mechanism of stem cell specification which explains why only some stem cells adopt a muscle cell fate. ... the team would now focus on unravelling the mechanisms of embryonic muscle cell differentiation at the molecular level as a necessary step to regulating regeneration of the muscles in human patients."

Link: http://www.monash.edu.au/news/show/stem-cell-study-could-pave-the-way-to-treatment-for-age-related-muscle-wasting

From the SENS Foundation: "SENS Foundation is a 501c3 non-profit which works to develop, promote and ensure widespread access to rejuvenation biotechnologies which comprehensively address the disabilities and diseases of aging. The Foundation combines significant direct research efforts with education, affiliation and outreach programs. The SENS Foundation Academic Initiative (AI) is the nexus of its educational activities, which includes student mentoring, small but growing grants and scholarship programs, and coursework development. SENS Foundation is seeking a staff member to be Academic Coordinator. The Academic Coordinator will oversee the Academic Initiative and be responsible for designing, implementing and expanding projects and programs that support the aims of SENS Foundation. Additional responsibilities will include managing AI volunteer staff and students; maintaining active communication with SENS Foundation management, the Foundation Research Center, and AI volunteers; and establishing and maintaining reporting measures to document AI operations. The AC will report to the CEO, and work closely with the CSO, Vice President, and Director of Research Operations. Major projects already in development include the creation of online undergraduate courses in longevity science, development of a comprehensive training program, continuance and expansion of the scholarship and mentoring program, and implementation of a comprehensive marketing strategy to expand and promote the Academic Initiative."

Link: http://www.sens.org/node/2017

Many lower animals can regenerate from injuries that mammals cannot naturally heal - yet the fundamental components of their biology are much the same when considered at a high level. It's all cells and signalling molecules under the hood, and we're all sitting on branches of the same evolutionary tree. So it seems very plausible that there is something to be learned about regeneration from the biochemistries of species that can regrow lost limbs, completely heal heart injuries, or even grow half a body when needs must. Here is a small selection of research from the past week or so, illustrative of the work of a number of scientists investigating animals ranging from flatworms to salamanders.

Zebrafish Regrow Fins Using Multiple Cell Types, Not Identical Stem Cells

What does it take to regenerate a limb? Biologists have long thought that organ regeneration in animals like zebrafish and salamanders involved stem cells that can generate any tissue in the body. But new research suggests that multiple cell types are needed to regrow the complete organ, at least in zebrafish.

...

Limb regeneration has long captured people's imaginations.Traditionally, when people have looked at how a limb regenerates, they see a group of cells forming at the amputation site and the cells all look the same. So they've imagined that these cells have lost their identities and can become anything else. Our results show that this is not the case in the zebrafish fin. And there is mounting evidence that this is not the case in the salamander limb. ... This is evidence that we can't necessarily do regenerative medicine by plopping in generalized stem cells. The key may be to induce the cells that are already there to grow again. We need to understand and account for every cell lineage and then convince them to play ball together.

And just to show that there's no consistency whatsoever in nature, the story for the humble planarian appears to be quite the opposite.

Pluripotent adult stem cells power planarian regeneration

Ever since animals, such as lizards and starfish, were observed regenerating missing body parts, people have wondered where the new tissues come from. In the case of the planarian flatworm, Whitehead Institute researchers have determined that the source of this animal's extraordinary regenerative powers is a single, pluripotent cell type.

...

This is an animal that, through evolution, has already solved the regeneration problem. We're studying planarians to see how their regeneration process works. And, one day, we'll examine what are the key differences between what's possible in this animal and what's possible in a mouse or a person.

Heads or tails? Worm with abundant ability to regenerate relies on ancient gene to make decisions

This amazing ability of the planarian flatworm to regenerate its entire body from a small wedge of tissue has fascinated scientists since the late 1800s. The worms can regrow any missing cell or tissue - muscle, neurons, epidermis, eyes, even a new brain. Now Petersen and colleague Peter Reddien of the Massachusetts Institute of Technology (MIT) have discovered that an ancient and seldom-studied gene is critical for regeneration in these animals. The findings may have important ramifications for tissue regeneration and repair in humans.

...

In the paper, the authors describe how the gene notum acts at head-facing wounds as a dimmer switch to dampen the Wnt pathway and promote head regeneration. When the head or tail of a planarian is cut off, Wnt is activated. This Wnt activity turns on notum, but only at head-facing wounds. In a feedback loop, notum then turns Wnt down low enough that it can no longer prevent a head from forming. In tail-facing wounds, however, notum is not activated highly, a condition that promotes tail regrowth. (It takes the worm about a week to regrow a head or tail.)

The researchers are intrigued by this new role for notum. Like the Wnt signaling pathway, notum is highly conserved throughout species, from sea anenomes to fruit flies to humans, but little is known about its roles in biology. Because both notum and the Wnt signaling pathway are so evolutionarily ancient, their interaction in planarians may indicate a relationship that is important in other animals as well.

Wnt appears in a lot of published research into regeneration - it's clearly important in these processes, and the more that becomes known about the signalling systems of which it is a part, the better.

Promising news: "A team of researchers [has] now compared the ability of cells derived from different types of human stem cell to reverse disease in a rat model of Parkinson disease and identified a stem cell population that they believe could be clinically relevant. ... Parkinson disease results from the progressive loss of a specific subpopulation of nerve cells. Current treatments provide only relief from the symptoms of the disease and cannot reverse the nerve cell loss. Stem cells are considered by many to be promising candidate sources of cells to reverse nerve cell loss in individuals with Parkinson disease through their ability to regenerate and repair diseased tissues. ... There are two types of stem cell considered in this context: embryonic stem (ES) cells, which are derived from early embryos; and induced pluripotent stem (iPS) cells, which are derived by reprogramming cells of the body such that they have the ability to generate any cell type. In turn, cells of the body can be reprogrammed to become iPS cells in one of two ways: the reprogramming proteins can be transferred directly into the cells (protein-based iPS cells) or viruses can be used to deliver to the cells the genetic information necessary for producing the reprogramming proteins (virus-based iPS cell). [Researchers] found several problems with cells derived from virus-based human iPS cells that precluded their use in the Parkinson disease model but found that nerve cells derived from protein-based human iPS cells reversed disease when transplanted into the brain of rats modeling Parkinson disease. They therefore conclude that protein-based human iPS cells could be used in the treatment of individuals with Parkinson disease."

Link: http://www.sciencedaily.com/releases/2011/05/110516121419.htm

From EurekAlert!: researchers "are the first to regenerate large areas of damaged retinas and improve visual function using IPS cells (induced pluripotent stem cells) derived from skin. ... While other researchers have been successful in converting skin cells into induced pluripotent stem cells (iPSCs) and subsequently into retinal neurons, we believe that this is the first time that this degree of retinal reconstruction and restoration of visual function has been detected ... Today, diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are the leading causes of incurable blindness in the western world. In these diseases, retinal cells, also known as photoreceptors, begin to die and with them the eye's ability to capture light and transmit this information to the brain. Once destroyed, retinal cells, like other cells of the central nervous system have limited capacity for endogenous regeneration. ... Stem cell regeneration of this precious tissue is our best hope for treating and someday curing these disorders. ... [Researchers] harvested skin cells from the tails of red fluorescent mice. They used red mice, because the red tissue would be easy to track when transplanted in the eyes of non-fluorescent diseased mice. ... the group generated red fluorescent IPSCs, and, with additional chemical coaxing, precursors of retinal cells. ... Within 33 days the cells were ready to be transplanted and were introduced into the eyes of a mouse model of retina degenerative disease. ... Within four to six weeks, the researchers observed that the transplanted 'red' cells had taken up residence in the appropriate retinal area (photoreceptor layer) of the eye and had begun to integrate and assemble into healthily looking retinal tissue."

Link: http://www.eurekalert.org/pub_releases/2011-05/seri-so051611.php

Our descendants will look back on us with some horror: an era of peoples who could have largely saved themselves from oblivion, but didn't. Suicidal, negligent barbarians they'll call us - and they'll be right. We have had the tools to preserve the brains of the dead for the long haul for quite some time now, and preserve them well enough that the fine structures storing the data of the mind remain intact. Death is death, but oblivion only occurs when the present detailed arrangement of matter in your brain is destroyed. For so long as that data is preserved, there is the chance that future technology and circumstances will lead to a restoration of life, such as through the use of advanced nanotechnology and charitable groups dedicated to returning the preserved to active life once more.

The preserved have all the time in the world to wait, after all.

When we are stirred to think of it, we have a sort of horrified sympathy for our distant ancestors: peoples who lived brutish, painful, and shorter lives because they had no choice. Many thinkers of past ages envisaged a better world and better lives, with no hope of seeing that transpire with their own eyes. The same sentiment will be applied by our descendants to those who came a little way before us: doomed generations who could grasp at ideals and possibilities, but had no practical way to achieve these ends. Consider the words of Benjamin Franklin, for example:

I wish it were possible... to invent a method of embalming drowned persons, in such a manner that they might be recalled to life at any period, however distant; for having a very ardent desire to see and observe the state of America a hundred years hence, I should prefer to an ordinary death, being immersed with a few friends in a cask of Madeira, until that time, then to be recalled to life by the solar warmth of my dear country! But... in all probability, we live in a century too little advanced, and too near the infancy of science, to see such an art brought in our time to its perfection...

Sympathy is appropriate for those with high ideals and no possibility of ever achieving them - simply born too soon. But what of those who could achieve but turn aside and shirk the task? That would be us. I'd say we and our immediate forebears became suicidal, negligent barbarians about ten years after it became possible to build an industry to preserve brains, with a cost at scale that was affordable to the masses - on a par with funerals, for example.

For preservation methods along the lines of plastination, that point probably came and went somewhere in the 1930s or early 1940s, with the growth of the chemical industry into a true giant. The 1930s also saw the development of the first electron microscopes, and life scientists of the time arguably possessed enough knowledge of the cell to make educated guesses about which forms of chemical or low-temperature preservation would retain the data of the mind.

Here we stand, three generations removed, a thousand distinct human cultures in which there is little to show that we desire anything other than oblivion or self-delusion when it comes to our lives. Judging by actions rather than words, people who greatly desire both lasting life and health are a minority indeed. And with each passing year, another fifty million lives vanish into the maw to be destroyed utterly.

Some people can live moderately longer than others due to differences in their genes that enhance the ability of a good lifestyle to extend life, or blunt the tendency for a bad lifestyle to shorten life. In this age of biotechnology it is only a matter of time before all the biochemical differences between naturally longer-lived and shorter-lived human lineages are uncovered: "The development of medical interventions for the preservation of disease-free longevity would be facilitated by markers that predict healthy aging. Altered protein N-glycosylation patterns have been found with increasing age and several disease states. Here we investigate whether glycans derived from the total glycoprotein pool in plasma mark familial longevity and distinguish healthy from unhealthy aging. Total plasma N-glycan profiles of 2396 middle aged participants in the Leiden Longevity Study (LLS) were obtained ... After normalization and batch correction, several regression strategies were applied to evaluate associations between glycan patterns, familial longevity, and healthy aging. Two N-glycan features (LC-7 and LC-8) were identified to be more abundant in plasma of the offspring of long-lived individuals as compared to controls. ... Furthermore, a decrease in levels of LC-8 was associated with the occurrence of myocardial infarction, indicating that plasma glycosylation patterns do not only mark familial longevity but may also reflect healthy aging. In conclusion, we describe two glycan features, of which increased levels mark familial longevity and decreased levels of one of these features mark the presence of cardiovascular disease."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21184610

Researchers continue to investigate the effects of branched-chain amino acids (BCAA) on life span in laboratory animals: "Identification of strategies mimicking key [calorie restriction (CR)] mechanisms - increased mitochondrial respiration and reduced production of oxygen radicals - is a hot topic in gerontology. Dietary supplementation with essential and/or branched chain amino acids (BCAAs) exerts a variety of beneficial effects in experimental animals and humans and has been recently demonstrated to support cardiac and skeletal muscle mitochondrial biogenesis, prevent oxidative damage, and enhance physical endurance in middle-aged mice, resulting in prolonged survival. ... A body of recent evidence suggest that amino acids, and in particular BCAAs, behave as evolutionary conserved modulators of lifespan of different organisms ... [Like exercise, BCAA supplementation] does not affect maximum lifespan, but increases the median lifespan, an indicator that specific diseases have been prevented. ... A broad range of questions await answers. The first point to be clarified is the role that specific amino acid signatures can play, directly or indirectly, in the CR effects on healthspan. ... there is need to investigate which amino acid (or specific amino acid combination) is required for the beneficial effects seen in mammals. Not last in importance, large, randomized clinical trials are necessary to assess the safety and efficacy of BCAA/amino acid supplementation for the prevention and treatment of the disabling consequences of energy depletion in the elderly."

Link: http://www.impactaging.com/papers/v3/n5/full/100322.html

FIGHT AGING! NEWSLETTER
May 16th 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- SENS Foundation 2010 Year-End Report
- Open Biotech: the Lunch-Eating Helping Hand
- More on Body Temperature and Calorie Restriction
- Discussion
- Latest Headlines from Fight Aging!

SENS FOUNDATION 2010 YEAR-END REPORT

I strongly encourage you to read the entirety of the SENS Foundation year-end report for 2010. Progress is being made on the science; you'll find information on recent advances that you might not have heard about from other sources. Further, the Foundation has found its feet in the broader scientific community, and is now supported by many of the major figures in aging research. This bodes well for the next ten years of work on the biotechnologies of human longevity:

http://www.fightaging.org/archives/2011/05/sens-foundation-year-end-report-for-2010-now-available.php

"In 2009 we launched SENS Foundation. We did it to drive biomedical research towards a functional and cost-effective approach to extending individual health. We did it to raise awareness for an alternative to an increasingly complex and problematic pathology chase in medicine; to redefine regenerative medicine as applied to aging; to enable doctors to think about fixing patients before they were sick.

"We did it to transform the way you think about medicine. We knew it was a big agenda when we set out, and we were fully conscious of how small a public charity we were. We recognized that our first successful steps would depend upon our demonstration of fundamental credibility to the medical science community.

"That is why I am especially pleased to present this 2010 end of year report. As you will read, we have created a mature organization and delivered the networks and collaborations needed to build the rejuvenation biotechnology field. We've expanded our own research programs and have used that expansion to develop collaborations with leading universities and research institutions in regenerative medicine, around the nation and the world. We have, in short, found our voice with a substantial and mainstream scientific community. Rejuvenation biotechnology, as a research field, is emerging, and SENS Foundation has led that charge."

The work of the SENS Foundation is supported by the philanthropy of donors and patrons. If you like what you're reading, then you know what to do:

http://www.sens.org/take-action

OPEN BIOTECH: THE LUNCH-EATING HELPING HAND

Open biotechnology will reshape and accelerate the life science industry - including the development of working rejuvenation biotechnology - in the same way that open source software has shaped the the computing industry:

http://www.fightaging.org/archives/2011/05/the-lunch-eating-helping-hand-effect-of-open-biotech.php

"What are the effects of a large and energetic open development community on an industry? What happens when tens of thousands of people start making their products available for free, sharing data, designs, and improvements openly, and making money for services and expertise rather than through selling protected secrets? Fortunately we don't have speculate on this topic: we know. Look at the software industry, which is presently more vibrant and accomplished than it has ever been, whilst a large proportion of the most important software used around the world is open, freely shared, and constructed by a mix of professional and amateur contributors. Open source software is big business and that community gets things done.

"Why is this relevant? It is relevant because what happens in software today will happen in biotechnology tomorrow. The tools and techniques of biotechnology continue to fall in price, and the knowledge of how to use them is already spread widely beyond the ivory towers in which it originated. I'll note two interesting effects of a future large and bustling open development community in biotechnology: if you're managing a company that's in the business of biotech, then the open community will (a) constantly threaten to eat your lunch, and (b) help you and your employees be far more productive."

You should read the rest: the threat of lunch-eating is also a benefit, believe it or not.

MORE ON BODY TEMPERATURE AND CALORIE RESTRICTION

Some interesting comments on calorie restriction research and the biochemistry of natural longevity can be found in the following Fight Aging! post:

http://www.fightaging.org/archives/2011/05/more-on-body-temperature-and-calorie-restriction.php

"Individuals who significantly reduce their calorie intake have lower core body temperatures compared to those who eat more. The new finding matches research in animals. ... What we don't know is whether there is a cause/effect relationship or whether this is just an association. ... For now, animal models suggest that simply lowering body temperature isn't enough to increase lifespan. In mice and rats that regularly swam in cold water, core body temperature dropped due to exposure to the cold water. But those animals didn't live any longer than normal rodents. Fontana says it appears that how lower temperatures are achieved is important. 'I don't think it ever will be possible to be overweight and smoking and drinking and then take a pill, or several pills, to lower body temperature and lengthen lifespan,' he says. 'What may be possible, however, is to do mild calorie restriction, to eat a very good diet, get mild exercise and then take a drug of some kind that could provide benefits similar to those seen in severe calorie restriction.'"

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

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LATEST HEADLINES FROM FIGHT AGING!

N-ACYLETHANOLAMINES REQUIRED FOR CALORIE RESTRICTION
Friday, May 13, 2011
http://www.fightaging.org/archives/2011/05/n-acylethanolamines-required-for-calorie-restriction.php
Another part of the biochemical mechanisms of calorie restriction is uncovered in nematode worms: "The study [was] conducted on Caenorhabditis elegans (nematodes or roundworms), which are a widely accepted model for human aging research. ... Not only have we been able to identify some of these molecules for the first time in the worm, but we have also been able to show they act as a signal of nutrient availability and ultimately influence the worm's lifespan. What makes this important is that the same molecules are present in both humans and C. elegans, so these molecules may play similar roles in both organisms. ... The molecules identified in the new study are N-acylethanolamines (NAEs), a group of signaling molecules derived from lipids that help indicate nutrient availability in the environment and maintain an animal's internal energy balance. [Researchers showed that] NAE abundance in the worm is reduced during periods of dietary restriction, and that NAE deficiency in the presence of abundant food is sufficient to extend the animal's lifespan. ... It is well known that if you put C. elegans on a restricted diet, you can extend its lifespan by 40 to 50 percent. However, we were amazed to see that if you add back just one of these NAE molecules, eicosapentaenoyl ethanolamide, it completely abrogates the lifespan extension. ... Importantly, this particular NAE is similar to endocannabinoids in mammals, which regulate many different physiological processes including nutrient intake and energy balance, as well as inflammation and neuronal function."

LUNG STEM CELLS DISCOVERED
Friday, May 13, 2011
http://www.fightaging.org/archives/2011/05/lung-stem-cells-discovered.php
For a variety of reasons lung tissue engineering has lagged behind foundational work on other organs - but there are signs that it is catching up: researchers "have identified a human lung stem cell that is self-renewing and capable of forming and integrating multiple biological structures of the lung including bronchioles, alveoli and pulmonary vessels. ... This research describes, for the first time, a true human lung stem cell. The discovery of this stem cell has the potential to offer those who suffer from chronic lung diseases a totally novel treatment option by regenerating or repairing damaged areas of the lung ... Using lung tissue from surgical samples, researchers identified and isolated the human lung stem cell and tested the functionality of the stem cell both in vitro and in vivo. Once the stem cell was isolated, researchers demonstrated in vitro that the cell was capable of dividing both into new stem cells and also into cells that would grow into various types of lung tissue. Next, researchers injected the stem cell into mice with damaged lungs. The injected stem cells differentiated into new bronchioles, alveoli and pulmonary vessel cells which not only formed new lung tissue, but also integrated structurally to the existing lung tissue in the mice."

INDUCED PLURIPOTENT STEM CELLS VERSUS LIVER DAMAGE
Thursday, May 12, 2011
http://www.fightaging.org/archives/2011/05/induced-pluripotent-stem-cells-versus-liver-damage.php
More signs of progress in regenerative medicine: "researchers have demonstrated that human liver cells derived from adult cells coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage. ... liver cells derived from so-called "induced-pluripotent stem cells (iPSCs)" could one day be used as an alternative to liver transplant in patients with serious liver diseases, bypassing long waiting lists for organs and concerns about immune system rejection of donated tissue. ... iPSC-derived liver cells not only can be generated in large amounts, but also can be tailored to each patient, preventing immune-rejection problems associated with liver transplants from unmatched donors or embryonic stem cells. ... Although the liver can regenerate in the body, end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy the liver's regenerative ability ... Currently, the only option for those patients is to receive a liver organ or liver cell transplant, a supply problem given the severe shortage of donor liver tissue for transplantation. In addition, mature liver cells and adult liver stem cells are difficult to isolate or grow in the laboratory."

MITOCHONDRIAL DNA DAMAGE AND AGING STEM CELLS
Thursday, May 12, 2011
http://www.fightaging.org/archives/2011/05/mitochondrial-dna-damage-and-aging-stem-cells.php
Accumulating damage to mitochondrial DNA is one of the causes of aging, and here researchers investigate its role in the aging of stem cells: "Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model [that suffered a greater rate of mitochondrial DNA damage], we demonstrate hematopoietic defects reminiscent of premature [stem cell] aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging."

MTC PROTEINS, MITOCHONDRIA, AND AGING
Wednesday, May 11, 2011
http://www.fightaging.org/archives/2011/05/mtc-proteins-mitochondria-and-aging.php
News of another potential way to manipulate mitochondrial function to slow aging: "Mitochondria are the body's energy producers, the power stations inside our cells. Researchers [have] now identified a group of mitochondrial proteins, the absence of which allows other protein groups to stabilise the genome. This could delay the onset of age-related diseases and increase lifespan. ... When a certain MTC protein is lacking in the cell, e.g. because of a mutation in the corresponding gene, the other MTC proteins appear to adopt a new function. They then gain increased significance for the stabilisation of the genome and for combating protein damage, which leads to increased lifespan. These studies also show that this MTC-dependent regulation of the rate of aging uses the same signalling pathways that are activated in calorie restriction - something that extends the lifespan of many different organisms, including yeasts, mice and primates. Some of the MTC proteins identified in this study can also be found in the human cell, raising the obvious question of whether they play a similar role in the regulation of our own aging processes. It is possible that modulating the activity of the MTC proteins could enable us to improve the capacity of the cell to delay the onset of age-related diseases. These include diseases related to instability of the genome, such as cancer, as well as those related to harmful proteins, such as Alzheimer's disease and Parkinson's disease. At the moment this is only speculation, and the precise mechanism underlying the role of the MTC proteins in the aging process is a fascinating question that remains to be answered."

A POPULAR SCIENCE ARTICLE ON ORGAN PRINTING TECHNOLOGY
Wednesday, May 11, 2011
http://www.fightaging.org/archives/2011/05/a-popular-science-article-on-organ-printing-technology.php
From the Washington Post: "The machine looks like the offspring of an Erector Set and an inkjet printer. The 'ink' feels like applesauce and looks like icing. As nozzles expel the pearly material, layer by layer, you imagine the elaborate designs this device could make on gingerbread cookies. But the goo is made of living cells, and the machine is 'printing' a new body part. These machines - they're called three-dimensional printers - work very much like ordinary desktop printers. But instead of just putting down ink on paper, they stack up layers of living material to make 3-D shapes. The technology has been around for almost two decades, providing a shortcut for dentists, jewelers, machinists and even chocolatiers who want to make custom pieces without having to create molds. In the early 2000s, scientists and doctors saw the potential to use this technology to construct living tissue, maybe even human organs. They called it 3-D bioprinting, and it is a red-hot branch of the burgeoning field of tissue engineering. ... The possibilities for this kind of technology are limitless. Everyone has a mother or brother or uncle, aunt, grandmother who needs a meniscus or a kidney or whatever, and they want it tomorrow. ... The promise is exciting. The goal is not to squash that excitement, but to temper it with the reality of what the process is. ... The reality for now is that making such things as vertebral disks and knee cartilage, which largely just cushion bones, is far easier than constructing a complicated organ that filters waste, pumps blood or otherwise keeps a body alive. Scientists say the biggest technical challenge is not making the organ itself, but replicating its intricate internal network of blood vessels, which nourishes it and provides it with oxygen. Many tissue engineers believe the best bet for now may be printing only an organ's largest connector vessels and giving those vessels' cells time, space and the ideal environment in which to build the rest themselves; after that, the organ could be implanted."

BEN BOVA ON AGELESSNESS THROUGH FUTURE BIOTECHNOLOGY
Tuesday, May 10, 2011
http://www.fightaging.org/archives/2011/05/ben-bova-on-agelessness-through-future-biotechnology.php
An op-ed from writer Ben Bova: "'The first immortal human beings are probably living among us today.' That is the opening line of my 1998 nonfiction book, 'Immortality.' Today, more than a dozen years later, a growing number of research scientists and philosophers are beginning to sing much the same tune. They are speaking and writing about our post-human future, a coming era where human beings will be able to live youthful, vigorous, healthy lives for centuries or even longer. There might well be people alive today who may live for centuries, not as crumbling, aging wrecks, but as strong, youthful and active men and women. There is even evidence that aging itself might be not merely slowed or delayed, but actually reversed. One researcher, biogerentologist Aubrey de Grey, flatly states, 'I think the first person to live to a thousand might be 60 already.' Such views are certainly not mainstream. De Grey's detractors have called his ideas 'science fiction.' Yeah. Like space travel, nuclear power, lasers and pocket-sized computers." Bova's view of the medical technologies that will get us there is not complete - he focuses on a third of the overall picture as described in the Strategies for Engineered Negligible Senescence - but his vision of the future is right in the larger sense. The coming age will deliver rejuvenation biotechnology, and it is up to us to work to make that happen soon enough to matter.

WHY THE RESISTANCE TO ENGINEERED LONGEVITY?
Tuesday, May 10, 2011
http://www.fightaging.org/archives/2011/05/why-the-resistance-to-engineered-longevity.php
Thoughts from In Search of Enlightenment: "for the past 5 years or so, I have devoted the bulk of my time and energy contemplating the following question - why hasn't humanity undertaken an ambitious effort to advance the science that could help us redress the single leading cause of disease and death in the world today - namely, biological aging? What I have found most surprising, and alarming, in my teaching and research on this topic is the extent to which people will go to justify their intuition that we should not aspire to modify the current rate of the molecular and cellular decline of humans. These reasons typically range from sentiments like 'aging is natural' and 'doing so will exacerbate inequality', to 'it will cause overpopulation' and 'it will cause ecological disaster'. And yet no one raises these same objections when the discussion is about supporting the science which could help redress just one specific disease of aging - like cancer, heart disease or stroke. No one objects to medical research on stroke by claiming 'a disturbance in blood flow to the brain is natural' or 'preventing or curing strokes will exacerbate inequality' or 'all those people who would be saved from strokes will cause overpopulation or ecological disaster, so it is better they suffer a stroke'. Why not? Why is it that different moral sensibilities tend to be activated when the topic turns to modifying aging?"

OLD AGE IN THE FUTURE, AND A FAILURE OF THE IMAGINATION
Monday, May 9, 2011
http://www.fightaging.org/archives/2011/05/old-age-in-the-future-and-a-failure-of-the-imagination.php
This article on the future of being old talks about a failure of the imagination, the broad assumption by many people that their lives will look like the lives of their parents and grandparents in scope and length. Yet the article is itself a failure of the imagination - doing nothing more than projecting present slow trends, without looking at what is taking place in the laboratories. "It used to be that we knew what old age looked like. ... This was back when people over 65 accounted for a relatively small proportion of the US population - under 10 percent in 1960, according to the census from that year - and the average age at the time of death hovered under 70. Since then, advances in medicine and increasingly widespread health-consciousness have caused these numbers to rise precipitously. Demographers predict that by 2030, average life expectancy will have climbed past 80 and people over 65 will account for more than 20 percent of the country's population. ... Plenty has been said about how old age is changing now. But what will it be like for those of us who won't be hitting our 50th reunions for several more decades? Amid all the demographic projections, and all the worries about resources, we tend to assume that the actual texture of life as an old person in the future will be more or less what it is today - that even as old age lasts longer and becomes more prevalent in society, the concept itself, and the kind of life one associates with it, will remain intact. But this is a failure of imagination: In fact, old age in the future - particularly if you're looking at 2050 and later - promises to bear little resemblance to old age as it is experienced in 2011."

PATCHING A DAMAGED HEART
Monday, May 9, 2011
http://www.fightaging.org/archives/2011/05/patching-a-damaged-heart.php
Via ScienceDaily: researchers "have established a new method to patch a damaged heart using a tissue-engineering platform that enables heart tissue to repair itself. ... They were able, for the first time, to combine the use of human repair cells that were conditioned during in-vitro culture to maximize their ability to revascularize and improve blood flow to the infarcted tissue with a fully biological composite scaffold designed to deliver these cells to the damaged heart. With this platform, they could both keep the cells within the infarct bed (in contrast to the massive cell loss associated with infusion of cells alone) and enhance cell survival and function in the infarct bed, where most of the cells would have died because of the obstruction of their blood supply. ... [Researchers] removed the cells of a human heart muscle - the myocardium - leaving a protein scaffold with intact architecture and mechanical properties. They filled the scaffold with human mesenchymal progenitors (stem cells that can differentiate into many cell types) and then applied the patches to damaged heart tissue. The patches promoted the growth of new blood vessels and released proteins that stimulated the native tissue to repair itself."

______________________________

Biomedical gerontologist Aubrey de Grey is one of the figures appearing in the documentary film "How to Live Forever." It's played straight but isn't a serious piece, as this review notes:

It's a huge subject, vital to every living person in the world - what it means to grow old and how one can cheat or at least postpone mortality. Fortunately, Mark S. Wexler eschews ponderousness in favor of a wry, observant, open-minded approach in his most informative and often quite funny documentary How to Live Forever. ... The film opens May 13 in New York followed by a national expansion May 22.

Still, there you have Aubrey de Grey in theater distribution (again) - and the more folk to hear his message, the better. It's still the case that the vast majority of people are not aware of the state of the art in longevity science, the near term potential for progress towards the repair of aging, and how to help make it all happen. For all the work of advocates over the years, this message remains insufficiently repeated and too quiet.

Another commentary is entitled "A Little More Fear of Death, Please?":

The title is something of a misnomer: with his mother gone, and himself on the downslope of 50, Mark Wexler makes a general study of life-extension experts, self-proclaimed and otherwise. ... Wexler's "wisest" friend, Pico Iyer, tells him that death's finality makes sense of life (for who?), but the director barely addresses the fear of death [and] his grief over the loss of a parent is neither as intense nor as personal as, say, Ross McElwee's in Time Indefinite. ... Wexler settles on the lasting resonance of art as mortality's consolation prize. ... His film, though, is a cutesy binder of folk remedies offering inadequate balm.

A little more fear of death indeed - a sentiment I endorse. What's not to fear about the downward slope of degeneration, increasing frailty, pain, suffering, and the calm madness of a world that accepts all this and does next to nothing about it?

Another part of the biochemical mechanisms of calorie restriction is uncovered in nematode worms: "The study [was] conducted on Caenorhabditis elegans (nematodes or roundworms), which are a widely accepted model for human aging research. ... Not only have we been able to identify some of these molecules for the first time in the worm, but we have also been able to show they act as a signal of nutrient availability and ultimately influence the worm's lifespan. What makes this important is that the same molecules are present in both humans and C. elegans, so these molecules may play similar roles in both organisms. ... The molecules identified in the new study are N-acylethanolamines (NAEs), a group of signaling molecules derived from lipids that help indicate nutrient availability in the environment and maintain an animal's internal energy balance. [Researchers showed that] NAE abundance in the worm is reduced during periods of dietary restriction, and that NAE deficiency in the presence of abundant food is sufficient to extend the animal's lifespan. ... It is well known that if you put C. elegans on a restricted diet, you can extend its lifespan by 40 to 50 percent. However, we were amazed to see that if you add back just one of these NAE molecules, eicosapentaenoyl ethanolamide, it completely abrogates the lifespan extension. ... Importantly, this particular NAE is similar to endocannabinoids in mammals, which regulate many different physiological processes including nutrient intake and energy balance, as well as inflammation and neuronal function."

Link: http://www.eurekalert.org/pub_releases/2011-05/sri-srs050511.php

For a variety of reasons lung tissue engineering has lagged behind foundational work on other organs - but there are signs that it is catching up: researchers "have identified a human lung stem cell that is self-renewing and capable of forming and integrating multiple biological structures of the lung including bronchioles, alveoli and pulmonary vessels. ... This research describes, for the first time, a true human lung stem cell. The discovery of this stem cell has the potential to offer those who suffer from chronic lung diseases a totally novel treatment option by regenerating or repairing damaged areas of the lung ... Using lung tissue from surgical samples, researchers identified and isolated the human lung stem cell and tested the functionality of the stem cell both in vitro and in vivo. Once the stem cell was isolated, researchers demonstrated in vitro that the cell was capable of dividing both into new stem cells and also into cells that would grow into various types of lung tissue. Next, researchers injected the stem cell into mice with damaged lungs. The injected stem cells differentiated into new bronchioles, alveoli and pulmonary vessel cells which not only formed new lung tissue, but also integrated structurally to the existing lung tissue in the mice."

Link: http://www.eurekalert.org/pub_releases/2011-05/bawh-hls051011.php

Following up on recently published research into changes in body temperature brought about by the practice of calorie restriction in humans, I see that a release from a few days ago contains some interesting remarks from the researcher:

Individuals who significantly reduce their calorie intake have lower core body temperatures compared to those who eat more. The new finding matches research in animals. Mice and rats consuming fewer calories also have lower core body temperatures, and those animals live significantly longer than littermates eating a standard diet. ... What is interesting about that is endurance athletes, who are the same age and are equally lean, don't have similar reductions in body temperature.

...

What we don't know is whether there is a cause/effect relationship or whether this is just an association. But in animal studies, it's been consistently true that those with lower core body temperatures live longer. ... in an unrelated study called the Baltimore Longitudinal Study of Aging, scientists found that men who had lower core body temperatures, probably for genetic reasons, lived significantly longer than men with higher body temperatures. So it appears body temperature may predict longevity in humans, too.

...

For now, animal models suggest that simply lowering body temperature isn't enough to increase lifespan. In mice and rats that regularly swam in cold water, core body temperature dropped due to exposure to the cold water. But those animals didn't live any longer than normal rodents. Fontana says it appears that how lower temperatures are achieved is important. "I don't think it ever will be possible to be overweight and smoking and drinking and then take a pill, or several pills, to lower body temperature and lengthen lifespan," he says. "What may be possible, however, is to do mild calorie restriction, to eat a very good diet, get mild exercise and then take a drug of some kind that could provide benefits similar to those seen in severe calorie restriction."

Calorie restriction is chiefly interesting for its beneficial effects on health and longevity - which are nothing short of stunning in comparison to any presently available medical technology. It's the best present option for immediately and rapidly improving the health of basically healthy people. The evidence for it and the effects in studied human populations are so good that - if you are essentially healthy, in good shape, and would like to stay that way for as long as possible - you'd really have to have be digging for excuses not to be practicing calorie restriction.

All that said, calorie restriction is only slowing aging - and if we want to do better, to avoid becoming frail and aging to death, the only viable path forward is biotechnology along the lines of the Strategies for Engineered Negligible Senescence. If repair technologies for our biology are not developed soon enough, then all we gain through calorie restriction is a healthy life, probably a little longer, almost certainly with a lower cost of medical treatment and fewer chronic diseases of aging. To do better than that, to regain the vigor and health of youth and obtain extra decades of life, we need to support and encourage rapid advances in medical technology.

More signs of progress in regenerative medicine: "researchers have demonstrated that human liver cells derived from adult cells coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage. ... liver cells derived from so-called "induced-pluripotent stem cells (iPSCs)" could one day be used as an alternative to liver transplant in patients with serious liver diseases, bypassing long waiting lists for organs and concerns about immune system rejection of donated tissue. ... iPSC-derived liver cells not only can be generated in large amounts, but also can be tailored to each patient, preventing immune-rejection problems associated with liver transplants from unmatched donors or embryonic stem cells. ... Although the liver can regenerate in the body, end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy the liver's regenerative ability ... Currently, the only option for those patients is to receive a liver organ or liver cell transplant, a supply problem given the severe shortage of donor liver tissue for transplantation. In addition, mature liver cells and adult liver stem cells are difficult to isolate or grow in the laboratory."

Link: http://www.eurekalert.org/pub_releases/2011-05/jhmi-asc051011.php

Accumulating damage to mitochondrial DNA is one of the causes of aging, and here researchers investigate its role in the aging of stem cells: "Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model [that suffered a greater rate of mitochondrial DNA damage], we demonstrate hematopoietic defects reminiscent of premature [stem cell] aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21549326

I'll point out the results of a demographic and an associative study today: many of the leads followed up by life science researchers are first identified by showing there is some association between a particular trait or aspect of our biology and people who live longer, or have better health in old age. Firstly, I see that the Irish Longitudinal Study on Aging has published a weight of material, and a press release for those who like their summaries pre-digested:

TILDA is the most comprehensive study ever conducted on ageing in Ireland. Between 2009-2011, over 8,000 people aged 50 and over were randomly selected across the country and interviewed about many aspects of their lives including issues such as health, financial circumstances and quality of life. Almost 85 per cent of the participants also underwent a rigorous health assessment. The same group will be interviewed every two years until 2018.

...

A constant finding across the report is that those with higher levels of education and wealth are likely to enjoy better outcomes later in life.

Which reinforces data obtained from other large studies: the strong associations between wealth, intelligence, education, and health prospects in later life. These correlations have been discussed at Fight Aging! a number of times in past years. For example:

• Correlations in Biochemistry and Wealth
• Wealth and Longevity (for Individuals)
• Wealth and Longevity (for Populations)
• Revisiting the Link Between Intelligence and Longevity
• On Using the Tools to Hand

Moving on, you might recall hearing that grip strength is an excellent measure of frailty and thus risk of death in the old - and it correlates with all sorts of other measures of failing health and accumulating damage, such as the accumulation of AGEs. Here is another set of evidence in support of that biomarker:

We studied prospectively the midlife handgrip strength, living habits, and parents' longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu-Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965-1968, when they were 56-68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment.

...

Compared with people who died at the age of [less than] 79 years, centenarians belonged 2.5 times more often to the highest third of grip strength in midlife, were never smokers, had participated in physical activity outside work, and had a long-lived mother.

You can't do anything (yet) about the genes you were born with, but you can certainly work on the other line items listed above. You should expect good health to make a meaningful difference to your life expectancy - and bad health to make a meaningful difference in the opposite direction.

News of another potential way to manipulate mitochondrial function to slow aging: "Mitochondria are the body's energy producers, the power stations inside our cells. Researchers [have] now identified a group of mitochondrial proteins, the absence of which allows other protein groups to stabilise the genome. This could delay the onset of age-related diseases and increase lifespan. ... When a certain MTC protein is lacking in the cell, e.g. because of a mutation in the corresponding gene, the other MTC proteins appear to adopt a new function. They then gain increased significance for the stabilisation of the genome and for combating protein damage, which leads to increased lifespan. These studies also show that this MTC-dependent regulation of the rate of aging uses the same signalling pathways that are activated in calorie restriction - something that extends the lifespan of many different organisms, including yeasts, mice and primates. Some of the MTC proteins identified in this study can also be found in the human cell, raising the obvious question of whether they play a similar role in the regulation of our own aging processes. It is possible that modulating the activity of the MTC proteins could enable us to improve the capacity of the cell to delay the onset of age-related diseases. These include diseases related to instability of the genome, such as cancer, as well as those related to harmful proteins, such as Alzheimer's disease and Parkinson's disease. At the moment this is only speculation, and the precise mechanism underlying the role of the MTC proteins in the aging process is a fascinating question that remains to be answered."

Link: http://www.sciencedaily.com/releases/2011/05/110510074433.htm

From the Washington Post: "The machine looks like the offspring of an Erector Set and an inkjet printer. The 'ink' feels like applesauce and looks like icing. As nozzles expel the pearly material, layer by layer, you imagine the elaborate designs this device could make on gingerbread cookies. But the goo is made of living cells, and the machine is 'printing' a new body part. These machines - they're called three-dimensional printers - work very much like ordinary desktop printers. But instead of just putting down ink on paper, they stack up layers of living material to make 3-D shapes. The technology has been around for almost two decades, providing a shortcut for dentists, jewelers, machinists and even chocolatiers who want to make custom pieces without having to create molds. In the early 2000s, scientists and doctors saw the potential to use this technology to construct living tissue, maybe even human organs. They called it 3-D bioprinting, and it is a red-hot branch of the burgeoning field of tissue engineering. ... The possibilities for this kind of technology are limitless. Everyone has a mother or brother or uncle, aunt, grandmother who needs a meniscus or a kidney or whatever, and they want it tomorrow. ... The promise is exciting. The goal is not to squash that excitement, but to temper it with the reality of what the process is. ... The reality for now is that making such things as vertebral disks and knee cartilage, which largely just cushion bones, is far easier than constructing a complicated organ that filters waste, pumps blood or otherwise keeps a body alive. Scientists say the biggest technical challenge is not making the organ itself, but replicating its intricate internal network of blood vessels, which nourishes it and provides it with oxygen. Many tissue engineers believe the best bet for now may be printing only an organ's largest connector vessels and giving those vessels' cells time, space and the ideal environment in which to build the rest themselves; after that, the organ could be implanted."

Link: http://www.washingtonpost.com/national/science/2011/04/21/AFJM0WbG_print.html

Following on from the release of their 2010 research report, the SENS Foundation folk have issued their 2010 year-end report. Just as for the earlier research report, it is an interesting and closer look at the finances and research activities of the organization - one of the very few groups in the world whose leaders have the right idea when it comes to aging, longevity, and biotechnology.

In 2009 we launched SENS Foundation. We did it to drive biomedical research towards a functional and cost-effective approach to extending individual health. We did it to raise awareness for an alternative to an increasingly complex and problematic pathology chase in medicine; to redefine regenerative medicine as applied to aging; to enable doctors to think about fixing patients before they were sick.

We did it to transform the way you think about medicine. We knew it was a big agenda when we set out, and we were fully conscious of how small a public charity we were. We recognized that our first successful steps would depend upon our demonstration of fundamental credibility to the medical science community.

That is why I am especially pleased to present this 2010 end of year report. As you will read, we have created a mature organization and delivered the networks and collaborations needed to build the rejuvenation biotechnology field. We've expanded our own research programs and have used that expansion to develop collaborations with leading universities and research institutions in regenerative medicine, around the nation and the world. We have, in short, found our voice with a substantial and mainstream scientific community. Rejuvenation biotechnology, as a research field, is emerging, and SENS Foundation has led that charge.

If you like what you see, then help the Foundation achieve its mission. Donate, tell your friends, and write about what might be achieved soon through advanced biotechnology if there were just the will and the funding to do it. Bootstrapping a new industry and new view of medicine is a slow process, but every helping hand makes it faster.

An op-ed from writer Ben Bova: "'The first immortal human beings are probably living among us today.' That is the opening line of my 1998 nonfiction book, 'Immortality.' Today, more than a dozen years later, a growing number of research scientists and philosophers are beginning to sing much the same tune. They are speaking and writing about our post-human future, a coming era where human beings will be able to live youthful, vigorous, healthy lives for centuries or even longer. There might well be people alive today who may live for centuries, not as crumbling, aging wrecks, but as strong, youthful and active men and women. There is even evidence that aging itself might be not merely slowed or delayed, but actually reversed. One researcher, biogerentologist Aubrey de Grey, flatly states, 'I think the first person to live to a thousand might be 60 already.' Such views are certainly not mainstream. De Grey's detractors have called his ideas 'science fiction.' Yeah. Like space travel, nuclear power, lasers and pocket-sized computers." Bova's view of the medical technologies that will get us there is not complete - he focuses on a third of the overall picture as described in the Strategies for Engineered Negligible Senescence - but his vision of the future is right in the larger sense. The coming age will deliver rejuvenation biotechnology, and it is up to us to work to make that happen soon enough to matter.

Link: http://www.naplesnews.com/news/2011/may/07/ben-bova-may-8-2011-immortality-just-might-be-with/

Thoughts from In Search of Enlightenment: "for the past 5 years or so, I have devoted the bulk of my time and energy contemplating the following question - why hasn't humanity undertaken an ambitious effort to advance the science that could help us redress the single leading cause of disease and death in the world today - namely, biological aging? What I have found most surprising, and alarming, in my teaching and research on this topic is the extent to which people will go to justify their intuition that we should not aspire to modify the current rate of the molecular and cellular decline of humans. These reasons typically range from sentiments like 'aging is natural' and 'doing so will exacerbate inequality', to 'it will cause overpopulation' and 'it will cause ecological disaster'. And yet no one raises these same objections when the discussion is about supporting the science which could help redress just one specific disease of aging - like cancer, heart disease or stroke. No one objects to medical research on stroke by claiming 'a disturbance in blood flow to the brain is natural' or 'preventing or curing strokes will exacerbate inequality' or 'all those people who would be saved from strokes will cause overpopulation or ecological disaster, so it is better they suffer a stroke'. Why not? Why is it that different moral sensibilities tend to be activated when the topic turns to modifying aging?"

Link: http://colinfarrelly.blogspot.com/2011/05/life-extension-sacred-values-and-taboo_10.html

What are the effects of a large and energetic open development community on an industry? What happens when tens of thousands of people start making their products available for free, sharing data, designs, and improvements openly, and making money for services and expertise rather than through selling protected secrets? Fortunately we don't have speculate on this topic: we know. Look at the software industry, which is presently more vibrant and accomplished than it has ever been, whilst a large proportion of the most important software used around the world is open, freely shared, and constructed by a mix of professional and amateur contributors. Open source software is big business and that community gets things done.

Why is this relevant? It is relevant because what happens in software today will happen in biotechnology tomorrow. The tools and techniques of biotechnology continue to fall in price, and the knowledge of how to use them is already spread widely beyond the ivory towers in which it originated. I'll note two interesting effects of a future large and bustling open development community in biotechnology: if you're managing a company that's in the business of biotech, then the open community will (a) constantly threaten to eat your lunch, and (b) help you and your employees be far more productive.

Lunch-eating first. You can see this happening most clearly in the software world for databases, I think. Low-end databases are now a free product, even those that were once lines with licenses that sold for large sums of money. There is no market in software licenses for databases sold to small organization, because extremely good databases are free, reliable, and well known, thanks to the open source software community. The companies that produce databases have been driven out of the realm of low-hanging fruit and onward to achieve ever more challenging goals - to produce database products that can do things than were never done before, because there's no longer a market in doing what has been done.

This process of lunch-eating will continue: there is no point at which a database company will not have its present business model threatened by the inexorable progress of the open source development community. As soon as a company proves that a particular technical feat can be achieved, it is only a matter of time before that feat is replicated in a free database system.

In the near future, exactly this process will take hold for biotechnology and pharmaceutical companies. The growth of a large and well connected garage biotech / open biotech community will mean that new advances are reverse engineered and added to a growing repertoire of openly published methodologies - available to any group willing (or far enough away) to deal with the intellectual property issues. It will drive the for-profit producers and innovators onward and upward far faster than if their heels weren't being nipped.

And we all benefit from this. Faster progress and better results are far more important than letting a small number investors and employees have an easier time of it.

But onto the second effect, the helping hand. A company might have its lunch eaten at the low end of its market, but at the same time it benefits enormously from the fruits of the open development community. When good tools and the knowledge needed to use them are freely available, the cost of doing business falls: it becomes possible to achieve greater goals with the same level of investment. If you don't have to spend as much on the foundations and basic tools of the trade, then more of an investor's money is available for work on the cutting edge.

Thus an open development community enables far greater and more active innovation in the for-profit section of a field, and one of the ways it does this is by reducing the cost required for any given project to get started. A thriving open development community means that more people know how to accomplish foundational work, leading to easier hiring processes, and the tools for that work might well be free, or the next thing to it.

The wise investor or leader embraces an open development community - but as we've seen in the field of software development, that only happens after a period of trying to shut it all down. Large business are in the business of protectionism first and foremost, and they won't hesitate to co-opt the government in order to step on threats to their present status quo and income. They will do this regardless of how self-evident it is that an open development community benefits everyone, and regardless of how self-evident it is that trying to do this only hurts themselves in the long term.

Open development communities treat legal barriers as damage and route traffic and efforts around them - they are far less limited by geography and jurisdictions than large businesses, and are can react far more rapidly and effectively to threats or changing circumstances. At the same time, the economic benefits provided by open development are so large that they are hard for established closed development groups to resist forever. From the evolution of the software development community - open and closed - over the past few decades, we can see that open development essentially wins in the end, and those who stand in the way either destroy themselves or relent and join the party.

Again, this is the future of biotechnology - the next twenty years in garage biotech are loosely analogous to the period lasting from 1975 to 1995 in software development. It'll be an interesting ride. For my part, I see lunch-eating and the helping hand as very important underpinnings to the Vegas Group project. There isn't enough in the way of nipping at heels going on in the arena of longevity science, which is why we see potential technologies lying fallow, even though there are regions of the world in which they could be aggressively developed. The more reverse engineering and spreading of knowledge that takes place, the better, to my mind: everyone wins in the end with this as a fundamental force in the broader development community.

Pushing change through the FDA is a glacial and very expensive process of lobbying - a political process, naturally, which must be well lubricated with money that would be far better spent on research. This is what it is: essentially corrupt, utterly hostile to progress, a system in which the incentives are for regulators to cause delay and obstruction. .... I don't believe that we can afford to wait for the additional ten years or however many years it requires to win that fight, however. Not if there are other options on the table that may enable us to move faster. The Vegas Group approach is one such option: take the knowledge and techniques published by the research community into open biotech communities and overseas laboratories for further development, work them up to a level at which people are comfortable with the risks, and try them out. You get things done by getting things done.

This article on the future of being old talks about a failure of the imagination, the broad assumption by many people that their lives will look like the lives of their parents and grandparents in scope and length. Yet the article is itself a failure of the imagination - doing nothing more than projecting present slow trends, without looking at what is taking place in the laboratories. "It used to be that we knew what old age looked like. ... This was back when people over 65 accounted for a relatively small proportion of the US population - under 10 percent in 1960, according to the census from that year - and the average age at the time of death hovered under 70. Since then, advances in medicine and increasingly widespread health-consciousness have caused these numbers to rise precipitously. Demographers predict that by 2030, average life expectancy will have climbed past 80 and people over 65 will account for more than 20 percent of the country's population. ... Plenty has been said about how old age is changing now. But what will it be like for those of us who won't be hitting our 50th reunions for several more decades? Amid all the demographic projections, and all the worries about resources, we tend to assume that the actual texture of life as an old person in the future will be more or less what it is today - that even as old age lasts longer and becomes more prevalent in society, the concept itself, and the kind of life one associates with it, will remain intact. But this is a failure of imagination: In fact, old age in the future - particularly if you're looking at 2050 and later - promises to bear little resemblance to old age as it is experienced in 2011."

Link: http://boston.com/bostonglobe/ideas/articles/2011/05/08/seniorland_circa_2050/?page=full

Via ScienceDaily: researchers "have established a new method to patch a damaged heart using a tissue-engineering platform that enables heart tissue to repair itself. ... They were able, for the first time, to combine the use of human repair cells that were conditioned during in-vitro culture to maximize their ability to revascularize and improve blood flow to the infarcted tissue with a fully biological composite scaffold designed to deliver these cells to the damaged heart. With this platform, they could both keep the cells within the infarct bed (in contrast to the massive cell loss associated with infusion of cells alone) and enhance cell survival and function in the infarct bed, where most of the cells would have died because of the obstruction of their blood supply. ... [Researchers] removed the cells of a human heart muscle - the myocardium - leaving a protein scaffold with intact architecture and mechanical properties. They filled the scaffold with human mesenchymal progenitors (stem cells that can differentiate into many cell types) and then applied the patches to damaged heart tissue. The patches promoted the growth of new blood vessels and released proteins that stimulated the native tissue to repair itself."

Link: http://www.sciencedaily.com/releases/2011/05/110506171905.htm

FIGHT AGING! NEWSLETTER
May 9th 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- Eating and Lazing Your Way to a Shorter Life
- A Look at 55 Theses
- The Relentless Focus on Supplements is Not Helpful
- Merits of the Gung-Ho Argument for Immortality
- Discussion
- Latest Headlines from Fight Aging!

EATING AND LAZING YOUR WAY TO A SHORTER LIFE

Basic health practices aren't rocket science, and do make a respectable difference to the expected future of your health and longevity:

http://www.fightaging.org/archives/2011/05/eating-and-lazing-your-way-into-a-shorter-life.php

"A great many people eat too many calories and exercise too little. It's not as though the right amounts of either for generally good health are a state secret, but that doesn't seem to make a great deal of difference. Given the inch of luxury, most people will take the mile - and their health, life expectancy, and bank account all suffer for it. We did not evolve for optimal long-term functioning in a high calorie, sedentary environment, and it shows.

"This is an age upon the verge of developing biotechnologies of rejuvenation and general repair kits for all forms of damage to human tissue and bodily systems. Maybe you're young enough for the progressive advance of science to rescue you from the consequences of being an overfed, lazy lump ... but why risk it? A ten year difference in your life span or health span could mean missing the boat, dying prior to the advent of new medical technologies capable of repairing the damage that you yourself brought about. We're all on that same downward slope; why run faster towards the failure of your body and its component systems?"

A LOOK AT 55 THESES

55 Theses is a site that outlines, in a methodical, step by step way, the implications of an evolutionary view of human health, based on the work of researcher Michael Rose:

http://www.fightaging.org/archives/2011/05/a-look-at-55-theses.php

"I think it is a pity that most researchers don't in fact write a book or two outlining their view of science, the world, and progress at some point in their career. Scientific papers are a narrow and entirely insufficient window into a larger worldview, and many scientists have very broad and ambitious visions for the future of their field and the resulting technology. Michael Rose is one such scientist, and has written a few books along the way, of which I recommend the Long Tomorrow for an introduction to his view of aging and necessary strategic directions in the development of longevity science. My attention was recently drawn to a site called 55 Theses that goes a step further and assembles Rose's ideas in an online series of posts, videos, and small essays - and then asks
'knowing this, what can we do to make a difference in our own health and longevity?'"

I see this as an attempt to craft a movement much like the calorie restriction community: people focused on using scientific knowledge to slow aging as much as is possible through measured, considered diet and lifestyle choices.

THE RELENTLESS FOCUS ON SUPPLEMENTS IS NOT HELPFUL

If even a few percentage points of the vast supplement market's value went instead to real longevity science, we'd be much further along:

http://www.fightaging.org/archives/2011/05/the-relentless-focus-on-supplements-is-not-helpful.php

"Dietary supplements elbow their way into discussions of human longevity in a very unhelpful way. The loudest voice in the room when it comes to aging is not the research community, but rather the collective megaphone wielded by the salespeople of the 'anti-aging' marketplace - a well-funded army ever ready to puff up thin evidence, misrepresent research, propagate outright lies, and sell you whatever happens to be sitting in their warehouses right this instant. They're just as good at deceiving themselves as anyone else; the best salespeople are the true believers.

"This focus on supplements is, I think, some kind of oral fixation aspect of magical thinking. It's a mythic inheritance from the days of consuming a beast's heart to gain its courage. Researchers learn something about our biochemistry, spread the word, and that then manifests in our broader culture as an urge to consume some aspect of that knowledge - and so the pill sellers and potion manufacturers prosper in every age, regardless of the actual merits of what they sell."

MERITS OF THE GUNG-HO ARGUMENT FOR IMMORTALITY

Why not stand up and argue for things that are far beyond the bounds of the present debate? Someone has to be out there pushing out the goal posts and extending the scope of public discussion:

http://www.fightaging.org/archives/2011/05/merits-of-the-gung-ho-argument-for-immortality.php

"Public discourse is an arena of the timid, people who build their own cage of narrow visions and incremental goals. Without loud visionaries coming along to rattle the bars and point to the mountains in the distance, nothing would ever get done. Live to 150? Peanuts. If we enacted the goals of SENS, producing a rejuvenation biotechnology toolkit to repair the biochemical damage of aging, we'd all live for thousands of years if the present rate of fatal accidents continued as-is."

Someone has to point these things out, otherwise the entirety of the public debate over longevity science becomes "should we try to give people an extra couple of years, or should we just not bother at all."

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

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LATEST HEADLINES FROM FIGHT AGING!

WORK ON BOOSTING CELLULAR REPAIR PROCESSES
Friday, May 6, 2011
http://www.fightaging.org/archives/2011/05/work-on-boosting-cellular-repair-processes.php
This article looks at a research group who are working on a way to make cells more resilient to wear and tear - which may or may not have application to a range of conditions: "Their early research looked at skeletal muscle and how calcium plays a role in atrophy and aging. Then in 2006, they published a study showing cells in older mice were essentially leaking calcium - causing a natural aging process and inefficient muscle function. [Researchers] identified and isolated a naturally occurring protein that suggested [this aspect of the] aging process could possibly be reversed through future drugs. They subsequently gained worldwide attention after they identified the protein MG53 as a key initiator of membrane repair in damaged tissue, in the first study to specifically pinpoint a protein responsible for promoting cell repair. The protein is one that all humans, mice and other mammals have. It's a molecule at the forefront of repairing any and all injuries - from normal wear and tear of individual cells to widespread catastrophic trauma. The lab work shows the protein's importance under the microscope: A single needle prick completely deflates and kills a cell without the protein. But a cell bolstered with MG53 quickly recovers, repairing its torn outer layer at an accelerated rate. ... The research is now at the heart of a new drug company that is performing the first trials of an MG53 therapy on mice. ... the university granted TRIMedicine - headquartered in North Brunswick - a license to work on an application of the drug."

LATEST CIRM GRANTS MADE
Friday, May 6, 2011
http://www.fightaging.org/archives/2011/05/latest-cirm-grants-made.php
The latest grants made by the California Institute for Regenerative Medicine (CIRM): "The Governing Board of the California Institute for Regenerative Medicine, the State Stem Cell Agency, approved a $25 million award to support the first FDA-approved clinical trial based on cells derived from human embryonic stem cells. The award to Menlo Park-based Geron, Corp, will support the company's on-going early phase trial for people with spinal cord injury. This is the first time the agency, which was created by the passage of proposition 71 in 2004, has funded a human clinical trial testing a stem cell-derived therapy. ... The initial phase of the trial will include just a small number of people with recent spinal cord injuries who will receive injections of oligodendrocyte progenitor cells derived from embryonic stem cells into the site of the injury. In animal models, those cells mature into oligodendrocytes, which produce the insulating layer surrounding neurons. The initial phase of the three-year project is designed to test whether the cells are safe. Later phases will include different levels of spinal cord injury and will test increasing doses of the cells. ... At the same meeting, the Governing Board approved 27 Basic Biology III Awards worth $37.7 million. The awards to nine institutions will support research that leads to new insights in stem cell biology and disease origins. This work feeds the pipeline of new discoveries and also informs the work of research groups working on new disease therapies."

COMPLICATING THE PICTURE FOR CALORIE RESTRICTION AND FAT
Thursday, May 5, 2011
http://www.fightaging.org/archives/2011/05/complicating-the-picture-for-calorie-restriction-and-fat.php
A survey of calorie restriction in many mouse breeds finds that it doesn't work to extend healthy life in all, and that difference appears to be related to the degree to which calorie restriction results in fat loss. This presents an interesting complication, given that it has been clearly demonstrated that surgically removing visceral fat extends life in mice, and the human studies of calorie restriction show unambiguously positive results on health: "Since the 1930s scientists have proposed food restriction as a way to extend life in mice. Though feeding a reduced-calorie diet has indeed lengthened the life spans of mice, rats and many other species, new studies with dozens of different mouse strains indicate that food restriction does not work in all cases. ... [Researchers] studied the effect of food restriction on fat and weight loss in 41 genetically different strains of mice. The scientists then correlated the amount of fat reduction to life span. The answer: Mice that maintained their fat actually lived longer. Those that lost fat died earlier. ... Indeed, the greater the fat loss, the greater the likelihood the mice would have a negative response to dietary restriction, i.e., shortened life. This is contrary to the widely held view that loss of fat is important for the life-extending effect of dietary restriction. It turns the tables a bit."

WAKING UP THE IMMUNE SYSTEM WITH NANOPARTICLES
Thursday, May 5, 2011
http://www.fightaging.org/archives/2011/05/waking-up-the-immune-system-with-nanoparticles.php
The ability to make the immune system act in certain ways is the foundation for a range of powerful therapies: "scientists have discovered a way to wake up the immune system to fight cancer by delivering an immune system-stimulating protein in a nanoscale container called a vault directly into lung cancer tumors, harnessing the body's natural defenses to fight disease growth. The vaults, barrel-shaped nanoscale capsules found in the cytoplasm of all mammalian cells, were engineered to slowly release a protein, the chemokine CCL21, into the tumor. Pre-clinical studies in mice with lung cancer showed that the protein stimulated the immune system to recognize and attack the cancer cells, potently inhibiting cancer growth ... The vault nanoparticles containing the CCL21 have been engineered to slowly release the protein into the tumor over time, producing an enduring immune response. Although the vaults protect the packed CCL21, they act like a time-release capsule. ... [Researchers] plan to test the vault delivery method in human studies within the next three years and hope the promising results found in the pre-clinical animal tumor models will be replicated. ... The vault nanoparticle would require only a single injection into the tumor because of the slow-release design, and it eventually could be designed to be patient specific by adding the individual's tumor antigens into the vault ... The vaults may also be targeted by adding antibodies to their surface that recognize receptors on the tumor. The injection could then be delivered into the blood stream and the vault would navigate to the tumor, a less invasive process that would be easier on the patients. The vault could also seek out and target tumors and metastases too small to be detected with imaging."

VALIDATING A ROLE FOR INDUCED PLURIPOTENT STEM CELLS
Wednesday, May 4, 2011
http://www.fightaging.org/archives/2011/05/validating-a-role-for-induced-pluripotent-stem-cells.php
Researchers continue to put induced pluripotent stem cells (iPSCs) through their paces: "iPSCs, discovered in 2006, are derived by reprogramming adult cells into a primitive stem cell state. They are similar to [embryonic stem cells (ESCs)] in terms of their ability to differentiate into different types of cells in vivo, including endoderm cells that give rise to liver and lung tissue. ... induced pluripotent stem cells (iPSCs) can differentiate into definitive endoderm cells, in vitro, with similar functional potential when compared to embryonic stem cells (ESCs), despite minor molecular differences between the two cell types. These findings are particularly important given growing controversy in the scientific literature about whether subtle differences between iPSCs and ESCs should dampen enthusiasm for iPSCs to serve as an alternative source of differentiated precursor cells for various tissues, such as the liver, lung or blood. The new work provides compelling evidence that iPSCs have potential in regenerative medicine as an investigational tool for the development of treatments against diseases that affect endodermal-derived organs, such as cirrhosis, diabetes, cystic fibrosis and emphysema."

LONGEVITY DIFFERENCES WITHIN MOLE-RAT SPECIES
Wednesday, May 4, 2011
http://www.fightaging.org/archives/2011/05/longevity-differences-within-mole-rat-species.php
Long-lived naked mole-rats exhibit fairly large systematic differences in longevity within the species, and understanding the mechanisms may point the way to a class of therapies for aging: "African mole-rats (Bathyergidae, Rodentia) contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive 'helpers' in their natal families, often for several years. This 'reproductive subdivision' of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli), breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5 - 2.2fold depending on the sex), irrespective of social rank or other potentially confounding factors."

SURVEYING THE PRESENT USE OF FAT-DERIVED STEM CELLS
Tuesday, May 3, 2011
http://www.fightaging.org/archives/2011/05/surveying-the-present-use-of-fat-derived-stem-cells.php
One of the more widespread present uses of stem cells in the clinic involves cells derived from a patient's own fat tissue. Here an Indian publication surveys the landscape: "Stem cells offer exciting medical promise for repairing or replacing organs that are diseased, damaged or worn out. This promise of repair and regeneration was taken a step further with the advent of Adipose (Fat) Derived Stem Cells (ADSC) which are derived from our own excess body fat. Much like recycling waste, our excess fat can be processed to give us a better quality of life. Currently used for breast augmentation and reconstruction as well as plastic surgery, ADSC are being researched for most debilitating diseases like Myocardial Infarction (MI), diabetes mellitus and neurodegenerative diseases also. ... Clinically, ADSCs have the advantage over their bone marrow-derived counterparts, because of their abundance in numbers - eliminating the need for culturing over days to obtain a therapeutically viable number - and the ease of the harvest procedure itself - being less painful than the harvest of bone marrow. This, in theory, means that an autologous transplant of ADSC will not only work in much the same way as the successes shown using marrow-derived mesenchymal stem cell transplant, but also be of minimal risk to the patient. ... I was a part of adipose tissue derived stem cell trial in spinal cord injury and critical limb ischemia. We could not have a large number of subjects because of cost considerations, but the results were encouraging in spinal cord injury. However in critical limb ischemia results were poor as compared to good results of other studies with bone marrow derived stem cells ... Apart from these cases, Mumbai based Kasiak Research is using ADSC for idiopathic pulmonary fibrosis. ... Apart from this, there are a number of trials investigating applications in ischemic heart disease around the world."

ON CALORIE RESTRICTION AND HEALTH
Tuesday, May 3, 2011
http://www.fightaging.org/archives/2011/05/on-calorie-restriction-and-health.php
A paper that captures the present mainstream view on calorie restriction in humans: "There is increasing evidence that restricting caloric intake may have considerable health benefits in humans. Significant evidence in non-primate animals demonstrates that caloric restriction increases average and maximal life span. However, historically, caloric intake reduction in humans has been involuntary and accompanied by poverty, malnutrition, poor sanitation, and a lack of modern health care. As a result, caloric restriction in people typically has been accompanied by a reduction of both average and maximal life span. Conversely, improvements in standards of living usually are accompanied by an increased food supply and resultant improved health and longevity. The majority of the world is now in a new era where an abundance of caloric intake and its associated obesity are causing widespread chronic illness and premature death. What would happen if one were to institute caloric restriction with high-quality nutrition within an environment of modern sanitation and health care? This review argues that improved health and improved average life span would quite likely result. A lengthening of maximal human life span with this combination is perhaps possible but by no means certain."

AN EARLY IMMUNE THERAPY TRIAL FOR MELANOMA
Monday, May 2, 2011
http://www.fightaging.org/archives/2011/05/an-early-immune-therapy-trial-for-melanoma.php
Immune therapies are slowly making their way into clinical trials: in recent work, researchers "harvested immune cells from nine patients. They souped up the cells in their lab - in effect giving them the ability to remember cancer cells - multiplied them in number, and infused them back into the patients from whom they been taken. This technique, called adoptive t-cell therapy, primes the immune system to seek out and destroy cancer cells throughout the body. Ten weeks after starting the therapy, seven of the nine patients had more of the specially trained cells than they had started with. The disease in four of the patients had become stable - neither advancing nor retreating. In one patient, the cancer disappeared completely; two years later, it has still not returned. ... The work is not yet ready for commercialization. Laboratory methods for boosting immune cells need to be perfected and made more efficient, and more early clinical trials are needed. ... Five of the [patients] went on to take ipilimumab, a human monoclonal antibody ... With the addition of ipilimumab, [tumors] shrank in three of the five patients and stopped growing in the other two, a response far better than that shown in previous trials of the drug. [This suggests] immunotherapy may help drugs work better."

GENE THERAPY VERSUS AGE-RELATED MACULAR DEGENERATION
Monday, May 2, 2011
http://www.fightaging.org/archives/2011/05/gene-therapy-versus-age-related-macular-degeneration.php
From EurekAlert!: "A gene therapy approach using a protein called CD59, or protectin, shows promise in slowing the signs of age-related macular degeneration (AMD), according to a new in vivo study ... CD59 delivered by a gene therapy approach significantly reduced the uncontrolled blood vessel growth and cell death typical of AMD, the most common cause of blindness in the elderly. ... Activation of the complement system, a part of the immune system, is responsible for slowly killing cells in the back of the eye, leading to AMD. Activation of this system leads to the generation of pores or holes known as 'membrane attack complex' or MAC in cell membranes. CD59 is known to block the formation of MAC. ... CD59 is unstable and hence previous studies using CD59 have had limited success. The gene therapy approach that we developed continuously produces CD59 in the eye and overcomes these barriers, giving us renewed hope that it can be used to fight the progression of AMD and potentially other diseases. ... [Researchers] delivered CD59 to the eye using a deactivated virus similar to one previously shown to be safe in humans. Using an established mouse model of age-related macular degeneration, they found that eyes treated with CD59 had 62 percent less uncontrolled blood vessel growth and 52 percent less MAC than controls. ... Treatment was effective when administered at a very specific location beneath the retina, but importantly, also when it was administered to the center of the eye. This finding is especially encouraging because it would allow for a safer and more convenient route of administration of treatment."

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In the course of gently publicizing the Vegas Group project across recent weeks, I have been reminded that most people assume Reason to be a pseudonym. It isn't - Reason is actually my name. The way this works in the offline world, face to face, is much as follows:

Rude Person: Your name is Reason? Really? Really?

Me: Yes.

Rude Person: Oh.

And there it stops.

In the online world, sad to say, it is never that simple. To a certain extent I blame the growth of social network culture for the present level of confusion regarding privacy, anonymity, and abuse of anonymity - people have a way of conflating these three into one, when they are in fact quite separate items. Within the world of Facebook and the like, surrounded by the illusion of transparent vision into every trivial detail of the lives of others, people are forgetting both the simple courteous act of respecting privacy and the important differences between privacy and anonymity.

It should be remembered that the view of the lives of others provided by social networks is a fake: you are looking at a front, a presented facade. The only difference between that and email conversations - or exchanges of written letters - lies in the level of detail and immediacy. But I think that the ersatz appearance of lives lived like an open book cultivates a corrosive sense of entitlement quite unlike the cultural changes brought on by earlier forms of mass communication: that one is entitled to know a great deal about any other person, irrespective of their wishes on the subject. This is grossly impolite and disrespectful when carried from thought into action. Courtesy and privacy are intimately linked, and respect for a person must include a respect for their boundaries of privacy.

As it happens, I am a very private individual, something of a dying breed these days. I do not use social networks, as I gain little value from them. It isn't within my comfort zone for you to know where I work, what I look like, where I live, how I like my toast cooked, who I hang out with, who I connect with, and the thousand other trivialities that make up the evolving social network culture of zealous and carefully gardened oversharing. More and more often these days, I am finding that the response to my desired level of privacy is outright hostility - that a person feels entitled to know these things about me, and that this knowledge is in some way required for even the most trivial of communications.

This would no doubt seem ridiculous to our ancestors of past centuries, who communicated their thoughts to the distant reaches of the world in long-form essays. A person was judged from afar by their words, and the name attached to those words was the most trivial of identifiers. If you cannot produce a measured response to the messages contained in the hundreds of thousands of words that comprise Fight Aging!, then how is knowing what I look like going to help you? It won't, of course, and neither will knowing how I like my toast cooked.

In short, I am private, not anonymous - and that fact shouldn't matter one way or another. Judge by words and actions, not by characteristics that have little relationship to either. For the vocal few who apparently care deeply about such things, I'll point out that you would have said nothing and felt fine if the tagline on this blog and my emails said "John Smith" or some other form of bland, generic name. Doesn't that indicate that your approach to considering anonymity is broken in some fundamental way?

This article looks at a research group who are working on a way to make cells more resilient to wear and tear - which may or may not have application to a range of conditions: "Their early research looked at skeletal muscle and how calcium plays a role in atrophy and aging. Then in 2006, they published a study showing cells in older mice were essentially leaking calcium - causing a natural aging process and inefficient muscle function. [Researchers] identified and isolated a naturally occurring protein that suggested [this aspect of the] aging process could possibly be reversed through future drugs. They subsequently gained worldwide attention after they identified the protein MG53 as a key initiator of membrane repair in damaged tissue, in the first study to specifically pinpoint a protein responsible for promoting cell repair. The protein is one that all humans, mice and other mammals have. It's a molecule at the forefront of repairing any and all injuries - from normal wear and tear of individual cells to widespread catastrophic trauma. The lab work shows the protein's importance under the microscope: A single needle prick completely deflates and kills a cell without the protein. But a cell bolstered with MG53 quickly recovers, repairing its torn outer layer at an accelerated rate. ... The research is now at the heart of a new drug company that is performing the first trials of an MG53 therapy on mice. ... the university granted TRIMedicine - headquartered in North Brunswick - a license to work on an application of the drug."

Link: http://www.nj.com/news/index.ssf/2011/05/in_a_umdnj_lab_a_discovery_tha.html

The latest grants made by the California Institute for Regenerative Medicine (CIRM): "The Governing Board of the California Institute for Regenerative Medicine, the State Stem Cell Agency, approved a $25 million award to support the first FDA-approved clinical trial based on cells derived from human embryonic stem cells. The award to Menlo Park-based Geron, Corp, will support the company's on-going early phase trial for people with spinal cord injury. This is the first time the agency, which was created by the passage of proposition 71 in 2004, has funded a human clinical trial testing a stem cell-derived therapy. ... The initial phase of the trial will include just a small number of people with recent spinal cord injuries who will receive injections of oligodendrocyte progenitor cells derived from embryonic stem cells into the site of the injury. In animal models, those cells mature into oligodendrocytes, which produce the insulating layer surrounding neurons. The initial phase of the three-year project is designed to test whether the cells are safe. Later phases will include different levels of spinal cord injury and will test increasing doses of the cells. ... At the same meeting, the Governing Board approved 27 Basic Biology III Awards worth $37.7 million. The awards to nine institutions will support research that leads to new insights in stem cell biology and disease origins. This work feeds the pipeline of new discoveries and also informs the work of research groups working on new disease therapies."

Link: http://cirm.ca.gov/pressrelease_2011-05-04

I think it is a pity that most researchers don't in fact write a book or two outlining their view of science, the world, and progress at some point in their career. Scientific papers are a narrow and entirely insufficient window into a larger worldview, and many scientists have very broad and ambitious visions for the future of their field and the resulting technology. Michael Rose is one such scientist, and has written a few books along the way, of which I recommend the Long Tomorrow for an introduction to his view of aging and necessary strategic directions in the development of longevity science.

My attention was recently drawn to a site called 55 Theses that goes a step further and assembles Rose's ideas in an online series of posts, videos, and small essays - and then asks "knowing this, what can we do to make a difference in our own health and longevity?"

These theses are intended to supply a re-visioning of the scientific foundations of health and medicine. Rather than making small adjustments to a body of medical knowledge which has been developing by accretion since the time of Hippocrates, this re-visioning starts with a firm rejection of the present reductionist foundations of medicine. The human body is not an inert vessel that can be fairly viewed in terms of a definable set of chemical reactions. Rather, it is a product of an evolutionary process that has been ongoing for billions of years, an evolutionary process that has been directed by natural selection. As such, it will be argued that evolutionary biology provides the only secure foundation for understanding our health and for improving the practice of medicine.

There is a lot of material there. If you'd like to wrap your head around an alternate scientific view of longevity, as a contrast to the repair biotechnology focus of this SENS-supporting author, I recommend taking an hour or two to walk through 55 Theses. In essence, it is a step by step overview that builds supporting evidence for specific changes in human lifestyle and diet that are predicted to lead to improved health and slower aging. In the end this largely boils down to "stop eating things that you are not well adapted to eat, from an evolutionary perspective."

Older adults from all human populations are not adequately adapted to agricultural patterns of nutrition and activity, resulting in an amplification of aging under such conditions.

Rose has bred breeding ever-longer lived flies for a great many years, and 55 Theses might be thought of as a framework for extending the same concepts to human practice - analogous to the way in which calorie restriction moved from the lab to a fair-sized community of scientifically-minded human practitioners. I see no reason why a Rosean lifestyle community couldn't arise in the same fashion: it would have a greater weight of scientific evidence behind it than most health-focused gatherings, though I think it has a little way to go in order to catch up with plain old calorie restriction and exercise in that regard. But if this is where the developer of 55 Theses is heading, more power to him I say.

So 55 Theses looks like a good attempt at a philosophy of scientific health practices, similar to the ethos of the calorie restriction community: act upon the implications of supported scientific knowledge of human biochemistry, so as to have the best chance possible of making the best use of our bodies over the long-term. There is uncertainty in all things, science included, and we're all aging - but that doesn't mean it's smart to run heedlessly forward, damaging yourself more than is necessary.

In the long run, good health practices may make the difference between living long enough to benefit from future rejuvenation biotechnology or dying just a few years short of the dawn of that golden era - and to my eyes that's where the value lies. If we were not within mere decades of developing the means to defeat aging, the common state of one's health would not be so profound an issue, I suspect.

A survey of calorie restriction in many mouse breeds finds that it doesn't work to extend healthy life in all, and that difference appears to be related to the degree to which calorie restriction results in fat loss. This presents an interesting complication, given that it has been clearly demonstrated that surgically removing visceral fat extends life in mice, and the human studies of calorie restriction show unambiguously positive results on health: "Since the 1930s scientists have proposed food restriction as a way to extend life in mice. Though feeding a reduced-calorie diet has indeed lengthened the life spans of mice, rats and many other species, new studies with dozens of different mouse strains indicate that food restriction does not work in all cases. ... [Researchers] studied the effect of food restriction on fat and weight loss in 41 genetically different strains of mice. The scientists then correlated the amount of fat reduction to life span. The answer: Mice that maintained their fat actually lived longer. Those that lost fat died earlier. ... Indeed, the greater the fat loss, the greater the likelihood the mice would have a negative response to dietary restriction, i.e., shortened life. This is contrary to the widely held view that loss of fat is important for the life-extending effect of dietary restriction. It turns the tables a bit."

Link: http://www.mysanantonio.com/news/article/UT-mouse-study-suggests-cutting-calories-may-not-1365206.php

The ability to make the immune system act in certain ways is the foundation for a range of powerful therapies: "scientists have discovered a way to wake up the immune system to fight cancer by delivering an immune system-stimulating protein in a nanoscale container called a vault directly into lung cancer tumors, harnessing the body's natural defenses to fight disease growth. The vaults, barrel-shaped nanoscale capsules found in the cytoplasm of all mammalian cells, were engineered to slowly release a protein, the chemokine CCL21, into the tumor. Pre-clinical studies in mice with lung cancer showed that the protein stimulated the immune system to recognize and attack the cancer cells, potently inhibiting cancer growth ... The vault nanoparticles containing the CCL21 have been engineered to slowly release the protein into the tumor over time, producing an enduring immune response. Although the vaults protect the packed CCL21, they act like a time-release capsule. ... [Researchers] plan to test the vault delivery method in human studies within the next three years and hope the promising results found in the pre-clinical animal tumor models will be replicated. ... The vault nanoparticle would require only a single injection into the tumor because of the slow-release design, and it eventually could be designed to be patient specific by adding the individual's tumor antigens into the vault ... The vaults may also be targeted by adding antibodies to their surface that recognize receptors on the tumor. The injection could then be delivered into the blood stream and the vault would navigate to the tumor, a less invasive process that would be easier on the patients. The vault could also seek out and target tumors and metastases too small to be detected with imaging."

Link: http://www.eurekalert.org/pub_releases/2011-05/uoc--usd042911.php

Dietary supplements elbow their way into discussions of human longevity in a very unhelpful way. The loudest voice in the room when it comes to aging is not the research community, but rather the collective megaphone wielded by the salespeople of the "anti-aging" marketplace - a well-funded army ever ready to puff up thin evidence, misrepresent research, propagate outright lies, and sell you whatever happens to be sitting in their warehouses right this instant. They're just as good at deceiving themselves as anyone else; the best salespeople are the true believers.

The simple truth is that no (presently available) supplement or collection of supplements can be shown to achieve anything close to the benefits to health and longevity produced by exercise and calorie restriction. Everyone should take a decent multivitamin, as it costs next to nothing and there is much evidence, both historical and contemporary, in support of the negative effects brought on by a diet lacking one or more essential micronutrients. The more adventurous can do as they please in the vast wilderness of studies showing very narrow statistical benefits in mice or specific populations - but only spend the money you can afford to throw away, and bear in mind you'd be better off donating it to efforts like the SENS Foundation that aim to actually repair and reverse aging rather than just slow it down. You'll never know whether or not all your investigations and supplements did any good: based on a broad reading of the work out there to date, any plausible effects from supplementation will be washed out by the consequences of your specific level of calorie intake and exercise.

This focus on supplements is, I think, some kind of oral fixation aspect of magical thinking. It's a mythic inheritance from the days of consuming a beast's heart to gain its courage. Researchers learn something about our biochemistry, spread the word, and that then manifests in our broader culture as an urge to consume some aspect of that knowledge - and so the pill sellers and potion manufacturers prosper in every age, regardless of the actual merits of what they sell.

I have to say that I am disappointed that Ray Kurzweil places so much emphasis on supplements in his thoughts on engineered longevity. He should throw that all out and focus on exercise and calorie restriction - that's where the science is far more settled, and the effects on health are large, noteworthy, and inarguable. But of course that isn't going to happen now that he has a business in the Life Extension Foundation vein going on that side, selling thin evidence to people who would rather follow the mythic path of eating knowledge than actually get up and exercise, or sanely reduce their intake of calories.

Researchers continue to put induced pluripotent stem cells (iPSCs) through their paces: "iPSCs, discovered in 2006, are derived by reprogramming adult cells into a primitive stem cell state. They are similar to [embryonic stem cells (ESCs)] in terms of their ability to differentiate into different types of cells in vivo, including endoderm cells that give rise to liver and lung tissue. ... induced pluripotent stem cells (iPSCs) can differentiate into definitive endoderm cells, in vitro, with similar functional potential when compared to embryonic stem cells (ESCs), despite minor molecular differences between the two cell types. These findings are particularly important given growing controversy in the scientific literature about whether subtle differences between iPSCs and ESCs should dampen enthusiasm for iPSCs to serve as an alternative source of differentiated precursor cells for various tissues, such as the liver, lung or blood. The new work provides compelling evidence that iPSCs have potential in regenerative medicine as an investigational tool for the development of treatments against diseases that affect endodermal-derived organs, such as cirrhosis, diabetes, cystic fibrosis and emphysema."

Link: http://www.medicalnewstoday.com/articles/223994.php

Long-lived naked mole-rats exhibit fairly large systematic differences in longevity within the species, and understanding the mechanisms may point the way to a class of therapies for aging: "African mole-rats (Bathyergidae, Rodentia) contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive 'helpers' in their natal families, often for several years. This 'reproductive subdivision' of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli), breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5 - 2.2fold depending on the sex), irrespective of social rank or other potentially confounding factors."

Link: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018757

I don't see anything wrong with standing up and arguing passionately for the merits of either immortality as a Platonic ideal or immortality as a practical goal. Here I take the colloquial modern meaning of agelessness attained through biotechnology rather than the old-school "never die, ever" variety of immortality attained only in stories and myths. But someone has to be out there pushing out the boundaries of the discussion:

The middle of the road, "reasonable" position in public or political debate tends to gravitate to midway between what are perceived to be the two opposite outrageous extremes, regardless of the actual merits of any of these positions. With this in mind, it is occurring to me that part of the ongoing problem in the modern political debate over healthy life extension is that our "outrageous extreme" has always been a tentative, reasonably proposal that medical research carry on and that near-term technology would seem to allow us all to live a little longer ... say, to 150.

Public discourse is an arena of the timid, people who build their own cage of narrow visions and incremental goals. Without loud visionaries coming along to rattle the bars and point to the mountains in the distance, nothing would ever get done. Live to 150? Peanuts. If we enacted the goals of SENS, producing a rejuvenation biotechnology toolkit to repair the biochemical damage of aging, we'd all live for thousands of years if the present rate of fatal accidents continued as-is.

So I'm always pleased to see people putting out opinions like this and provoking resulting discussions like this one at Hacker News:

I want to live forever. I've always thought that not dying was a pretty obvious thing to want. To my surprise, I've found that a lot of people whom I usually agree with on most topics strongly disagree with me on this one. Rather than write yet another piece extolling the virtues of a far-future post-scarcity post-singularity world, I thought I'd just document some of the objections to immortality I get and my counterarguments.

Note that for the purposes of giving my conversational partners opportunities to disagree, I typically posit a form of immortality where you, and you alone are presented with the option of eternal youth with no suicide option. You constantly regenerate to perfect health at the prime of your life. There are a lot of potential ways we might go about not dying, but people tend to find objections to this particular flavor more readily than the others. Please assume this working definition for the below.

Even discussion of the platonic ideal of immortality is, I think, useful provocation against the backdrop of advancing biotechnology that will be able to extend the human lifespan significantly in decades to come. Those advances won't happen by themselves: people need to work on them, support them, and demand them. An economy of longevity-enhancing biotechnology must arise, and for that there needs to be - at a minimum - a whole lot more people talking and thinking about the prospects.

One of the more widespread present uses of stem cells in the clinic involves cells derived from a patient's own fat tissue. Here an Indian publication surveys the landscape: "Stem cells offer exciting medical promise for repairing or replacing organs that are diseased, damaged or worn out. This promise of repair and regeneration was taken a step further with the advent of Adipose (Fat) Derived Stem Cells (ADSC) which are derived from our own excess body fat. Much like recycling waste, our excess fat can be processed to give us a better quality of life. Currently used for breast augmentation and reconstruction as well as plastic surgery, ADSC are being researched for most debilitating diseases like Myocardial Infarction (MI), diabetes mellitus and neurodegenerative diseases also. ... Clinically, ADSCs have the advantage over their bone marrow-derived counterparts, because of their abundance in numbers - eliminating the need for culturing over days to obtain a therapeutically viable number - and the ease of the harvest procedure itself - being less painful than the harvest of bone marrow. This, in theory, means that an autologous transplant of ADSC will not only work in much the same way as the successes shown using marrow-derived mesenchymal stem cell transplant, but also be of minimal risk to the patient. ... I was a part of adipose tissue derived stem cell trial in spinal cord injury and critical limb ischemia. We could not have a large number of subjects because of cost considerations, but the results were encouraging in spinal cord injury. However in critical limb ischemia results were poor as compared to good results of other studies with bone marrow derived stem cells ... Apart from these cases, Mumbai based Kasiak Research is using ADSC for idiopathic pulmonary fibrosis. ... Apart from this, there are a number of trials investigating applications in ischemic heart disease around the world."

Link: http://www.expresshealthcare.in/201105/knowledge01.shtml

A paper that captures the present mainstream view on calorie restriction in humans: "There is increasing evidence that restricting caloric intake may have considerable health benefits in humans. Significant evidence in non-primate animals demonstrates that caloric restriction increases average and maximal life span. However, historically, caloric intake reduction in humans has been involuntary and accompanied by poverty, malnutrition, poor sanitation, and a lack of modern health care. As a result, caloric restriction in people typically has been accompanied by a reduction of both average and maximal life span. Conversely, improvements in standards of living usually are accompanied by an increased food supply and resultant improved health and longevity. The majority of the world is now in a new era where an abundance of caloric intake and its associated obesity are causing widespread chronic illness and premature death. What would happen if one were to institute caloric restriction with high-quality nutrition within an environment of modern sanitation and health care? This review argues that improved health and improved average life span would quite likely result. A lengthening of maximal human life span with this combination is perhaps possible but by no means certain."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21526354

A great many people eat too many calories and exercise too little. It's not as though the right amounts of either for generally good health are a state secret, but that doesn't seem to make a great deal of difference. Given the inch of luxury, most people will take the mile - and their health, life expectancy, and bank account all suffer for it. We did not evolve for optimal long-term functioning in a high calorie, sedentary environment, and it shows. On this topic, allow me to point you to another couple of examples to add to the long litany of reasons to take better care of the health basics.

Packing on the pounds in middle age linked to dementia

Researchers studied information from the Swedish Twin Registry on 8,534 twins age 65 or older. ... The study found that people who were overweight or obese at midlife had an 80 percent higher risk of developing dementia, Alzheimer's disease or vascular dementia in late life compared to people with normal [body mass index]. The results remained the same after considering other factors, such as education, diabetes and vascular disease.

A little belly fat can double the risk of death in coronary artery disease patients

Researchers analyzed data from 15,923 people with coronary artery disease involved in five studies from around the world. They found that those with coronary artery disease and central obesity, measured by waist circumference and waist-to-hip ratio, have up to twice the risk of dying. That is equivalent to the risk of smoking a pack of cigarettes per day or having very high cholesterol, particularly for men.

This is an age upon the verge of developing biotechnologies of rejuvenation and general repair kits for all forms of damage to human tissue and bodily systems. Maybe you're young enough for the progressive advance of science to rescue you from the consequences of being an overfed, lazy lump ... but why risk it? A ten year difference in your life span or health span could mean missing the boat, dying prior to the advent of new medical technologies capable of repairing the damage that you yourself brought about.

We're all on that same downward slope; why run faster towards the failure of your body and its component systems?

Immune therapies are slowly making their way into clinical trials: in recent work, researchers "harvested immune cells from nine patients. They souped up the cells in their lab - in effect giving them the ability to remember cancer cells - multiplied them in number, and infused them back into the patients from whom they been taken. This technique, called adoptive t-cell therapy, primes the immune system to seek out and destroy cancer cells throughout the body. Ten weeks after starting the therapy, seven of the nine patients had more of the specially trained cells than they had started with. The disease in four of the patients had become stable - neither advancing nor retreating. In one patient, the cancer disappeared completely; two years later, it has still not returned. ... The work is not yet ready for commercialization. Laboratory methods for boosting immune cells need to be perfected and made more efficient, and more early clinical trials are needed. ... Five of the [patients] went on to take ipilimumab, a human monoclonal antibody ... With the addition of ipilimumab, [tumors] shrank in three of the five patients and stopped growing in the other two, a response far better than that shown in previous trials of the drug. [This suggests] immunotherapy may help drugs work better."

Link: http://www.technologyreview.com/biomedicine/37480/

From EurekAlert!: "A gene therapy approach using a protein called CD59, or protectin, shows promise in slowing the signs of age-related macular degeneration (AMD), according to a new in vivo study ... CD59 delivered by a gene therapy approach significantly reduced the uncontrolled blood vessel growth and cell death typical of AMD, the most common cause of blindness in the elderly. ... Activation of the complement system, a part of the immune system, is responsible for slowly killing cells in the back of the eye, leading to AMD. Activation of this system leads to the generation of pores or holes known as 'membrane attack complex' or MAC in cell membranes. CD59 is known to block the formation of MAC. ... CD59 is unstable and hence previous studies using CD59 have had limited success. The gene therapy approach that we developed continuously produces CD59 in the eye and overcomes these barriers, giving us renewed hope that it can be used to fight the progression of AMD and potentially other diseases. ... [Researchers] delivered CD59 to the eye using a deactivated virus similar to one previously shown to be safe in humans. Using an established mouse model of age-related macular degeneration, they found that eyes treated with CD59 had 62 percent less uncontrolled blood vessel growth and 52 percent less MAC than controls. ... Treatment was effective when administered at a very specific location beneath the retina, but importantly, also when it was administered to the center of the eye. This finding is especially encouraging because it would allow for a safer and more convenient route of administration of treatment."

Link: http://www.eurekalert.org/pub_releases/2011-04/tuhs-gts042911.php

FIGHT AGING! NEWSLETTER
May 2nd 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- A Vegas Group Initiative Update
- SENS Foundation is Hiring a LysoSENS Researcher
- Exploring Transdifferentiation
- Discussion
- Latest Headlines from Fight Aging!

A VEGAS GROUP INITIATIVE UPDATE

A couple of posts this week on the Vegas Group, which is at present a few folk focused on documenting the technique of protofection and getting the organizational basics figured out - more helping hands are always welcome:

http://www.fightaging.org/archives/2011/04/an-update-on-early-vegas-group-discussions.php

"The Vegas Group is presently a discussion list of a few active volunteers and a small crowd of interested folk. We are looking at the nuts and bolts of organization, focused on a proof of concept documentation project: take mitochondrial protofection and document it sufficiently well to make it accessible to the DIYbio community of enthusiasts and moonlighting biotech professionals who are building open-access devices and establishing shared laboratories. Along the way this means finding freelance life science writers, evangelizing the concept, proofing copy, making diagrams and layouts, and putting up a website - amongst other line items."

"We are looking for more life science and DIYbio volunteers, writers and editors, folk with connections that will help move things along, people with an understanding of the legalities of reverse engineering and intellectual property, and web developers who can help with the forthcoming website. Amongst others - if you think you can help make the Vegas Group a reality, then you probably can. So join the list and help!"

http://www.fightaging.org/archives/2011/04/potential-early-documentation-projects-for-the-vegas-group.php

"What is the Vegas Group initiative setting out to achieve, in a nutshell? I'm still working on that short explanation, but here is one attempt at it. Thanks to the present regulatory situation in the US - where aging is not recognized as a disease, and therefore no therapy for aging can be legally developed - there are any number of potentially useful biotechnologies presently languishing without further development. These are methods and techniques shown to extend life in mice or repair and reverse specific biochemical aspects of aging, but for which there is no further funding for clinical development. Nothing may be happening for these technologies in the US, but there are active biotechnology and medical development communities in other parts of the world who are not so encumbered by local regulation: many of the developed Asia-Pacific countries, for example. What the Vegas Group initiative ultimately aims to do is build a bridge between these undeveloped technologies and the developers who could bring them into the clinic for human use."

"How will that bridge be built? I believe that the growing garage biotechnology and DIYbio communities will play a pivotal role in the US - validating, documenting, and lowering the cost for overseas ventures to pick up and further develop longevity therapies. From my perspective then, the very earliest actions for the first Vegas Group volunteers involve building the foundations for a repository of how-to documentation: guides that clearly explain how the garage biotechnology community could validate and further develop the best and latest techniques in longevity science."

SENS FOUNDATION IS HIRING A LYSOSENS RESEARCHER

The SENS Foundation is hiring a team lead for their LysoSENS medical bioremediation research project:

http://www.fightaging.org/archives/2011/04/sens-foundation-is-hiring-for-the-lysosens-project.php

"LysoSENS is the SENS Foundation initiative to build a platform [capable] of breaking down the damaging byproducts of metabolism that build up in old cells and degrade their ability to recycle garbage. The short of is that we know that out there somewhere are bacteria that can eat these compounds, such as the lipofuscin that contributes to many age-related conditions. There is no buildup of prominent components of lipofuscin in graveyards, for example - so something is consuming it. That bacterial something will be armed with enzymes, biological knifes and saws that might be turned into a therapy to destroy lipofuscin if identified and introduced into the human body. ... The search for bacterial enzymes that can safely attack lipofuscin in the body presently gets the lion's share of research funding at the SENS Foundation, and, appropriately, they are hiring in the Bay Area, California."

EXPLORING TRANSDIFFERENTIATION

The field of stem cell research moves rapidly and is exceedingly complex, but is in essence the story of how researchers are learning to control cells - in particular how to change cells from one type into another. Some animal species do this naturally, in ways that might be advantageous for research programs in human medicine:

http://www.fightaging.org/archives/2011/04/ageless-animals-the-jellyfish-edition.php

"The jellyfish Turritopsis nutricula is one of the few species whose members might be considered immortal, based on what is presently known of its biology. ... The form of agelessness enjoyed by Turritopsis nutricula appears to be an adaptation to periods of starvation: it can retreat to earlier stages of its life cycle, and in the process its cells alter their character in an usual way ... Theoretically, it can repeat this process indefinitely as its cells undergo a process called transdifferentiation, a rare biological process whereby any non-stem cell can become a different cell entirely."

In recent years, researchers focused on transforming or culturing specific cell types through the intermediary stage of producing or obtaining stem cells. Thus you see a great deal of research focused on how to create stem cells from a patient's cells, or find sources of existing stem cells in the body - and then a great deal of research on how to instruct stem cells to differentiate into specific specialized cell types. But if researchers better understood the cell's instruction set, it should be possible to switch a cell's type directly without the need for stem cells:

http://www.fightaging.org/archives/2011/04/exploring-transdifferentiation-in-the-pancreas.php

"In recently reported research, researchers are making inroads in converting various types of cell in the pancreas - which offers the possibility of a fairly direct path towards providing new beta cells to diabetes patients ... Our work shows that beta cells and related endocrine cells can easily be converted into each other ... It had long been assumed that the identity of cells was 'locked' into place and that they could not be switched into other cell types. But recent studies have shown that some types of cells can be coaxed into changing into others - findings that have intensified interest in understanding the mechanisms that maintain beta cell identity."

Ultimately, this is all about lowering the cost of producing large numbers of any specific type of cell from easily obtained tissue samples from a patient (e.g. skin samples). The lower the cost, the more practical applications there are in a range of therapies.

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

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LATEST HEADLINES FROM FIGHT AGING!

CALORIE RESTRICTION INCREASES MITOCHONDRIAL BIOGENESIS
Friday, April 29, 2011
http://www.fightaging.org/archives/2011/04/calorie-restriction-increases-mitochondrial-biogenesis.php
Mitochondria are the cell's roving herd of bacteria-like power plants, and the damage they suffer in the course of their operation is strongly implicated as a contributing cause of aging. Here researchers show that calorie restriction appears to boost the rate at which new mitochondria are spawned: "mice with increased respiratory rates and reduced energetic conversion efficiency due to spontaneously uncoupled mitochondria lived longer than their counterparts. Indeed, different uncoupling strategies were able to extend lifespan in models ranging from yeast to mammals. ... uncoupling could be an approach to promote lifespan extension due to its ability to prevent the formation of reactive oxygen species (ROS). Indeed, mild mitochondrial uncoupling is a highly effective intervention to prevent the formation of ROS ... CR also increases the number of functional respiratory units (mitochondrial biogenesis) [and researchers] demonstrated that mitochondrial biogenesis was essential for many beneficial effects of dietary limitation in mice. ... We recently demonstrated that murine lifespan can be extended by low doses of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) in a manner accompanied by weight loss, lower serological levels of glucose, insulin and triglycerides as well as a strong decrease in biomarkers of oxidative damage and tissue ROS release. Similar effects have been repeatedly reported using CR diets ... Based on the similarities between these two interventions, we hypothesized that DNP treatment could also lead to enhanced mitochondrial biogenesis. In this manuscript, we measured the effects of DNP treatment and CR on mitochondrial biogenesis and associated pathways. We observed that both DNP and CR increase mitochondrial biogenesis, [confirming] that signaling events in both treatments converge."

A COMMENTARY ON METFORMIN STUDIES
Friday, April 29, 2011
http://www.fightaging.org/archives/2011/04/a-commentary-on-metformin-studies.php
A fairly long open access commentary on metformin and its effects on slowing aging in mice: "A recent study [may] certainly establish that metformin should be defined as geroprotective or gerosuppressant rather than bona fide [calorie restriction mimetic]. Long-living female mice from the outbred SHR strain were fed metformin in drinking water beginning at 3, 9 or 15 months of age and they were then analyzed for reproductive aging, mean and maximal lifespan and incidence of malignant tumors ... In female SHR mice, [researchers] now confirm that metformin treatment, if started early in life, notably increases by 21% the mean lifespan of tumor-free mice. In contrast, if started late in life, metformin treatment appears to significantly reduce (by 13%) the mean lifespan of tumor-free mice. ... It is perhaps relevant to note that, if started early in life, metformin treatment decreased the risk of death compared to the control group whereas similar treatment with metformin at older ages did not affect the relative risk of death in SHR female mice. Metformin's ability to increase the mean lifespan of tumor-free mice while simultaneously decreasing the risk of death in an age-related manner somewhat recapitulate metformin's ability to reduce cancer incidence among type 2 diabetic individuals."

CENTENARIANS AND OXIDATIVE STRESS
Thursday, April 28, 2011
http://www.fightaging.org/archives/2011/04/centenarians-and-oxidative-stress.php
A study of markers of oxidative stress in centenarians: "Human longevity is a complex phenotype that is determined by environment, genetics, and chance. Understanding the mechanisms by which aging leads to longevity, particularly healthy longevity would be of enormous benefit to our aging population. Unfortunately, most research on human aging has focused on phenomenological description of age-related diseases, and much less is known about the mechanisms of aging itself. Among the most promising theories about how and why we age is the Free Radical Theory, initially proposed by Denham Harman in 1956. Harman proposed that oxygen radicals produced during aerobic respiration induce oxidative damage in DNA, cells, tissues, and organisms that lead to aging and death. ... Harman hypothesized, based on observations of enzymatic redox chemistry, that oxygen radical generation occurs in vivo and that mechanisms exist to protect against such damage. Mitochondria were later found to be a principal source of these oxygen radicals ... Okinawa has among the world's longest-lived populations but oxidative stress in this population has not been well characterized. ... The low plasma level of [oxidized lipids] in Okinawan centenarians, compared to younger controls, argues for protection against oxidative stress in the centenarian population and is consistent with the predictions of the Free Radical Theory of Aging."

THOUGHTS ON PROTEIN AGGREGATION AND AGING
Thursday, April 28, 2011
http://www.fightaging.org/archives/2011/04/thoughts-on-protein-aggregation-and-aging.php
An open access paper: "Aging is the single most important risk factor in human disease in developed countries but when it comes to research on prevention or cures, aging is seldom taken into account. Nevertheless if aging is a significant contributor to age-related conditions, we would hope that an understanding of aging mechanisms could prompt the design of rational therapies. Moreover, if aging causes multiple diseases then it is reasonable to think that pharmacological agents that slow aging could be also effective in preventing or slowing a wide spectrum of diseases. ... Protein aggregation is a hallmark of aging and several age-related pathologies, collectively known as conformational diseases (CD). This similarity strongly suggests a crosstalk between aging and disease. Although it is not clear how protein aggregation occurs, dramatic alterations in the balance of protein synthesis, protein folding and protein degradation (together representing 'protein homeostasis') are likely to play important roles in this process. As a consequence, modified proteins tend to accumulate into soluble oligomers and insoluble aggregates that may actively influence cell function. Neurodegenerative diseases are arguably the best studied CD and the aberrant aggregation of several insoluble molecules [has] long been associated with the development of these pathologies. ... The general picture that that has emerged is that conformationally-altered proteins escape the surveillance of repair and degradation systems, form aggregates, and this process contributes to aging; aging could be therefore a manifestation of a loss in protein homeostasis. This then prompts the question: to what extent could chemical modulation of protein aggregation alter the rate of aging? Furthermore, would such an intervention influence disease pathology? In a recent publication, we addressed this issue by identifying small molecules able to slow protein aggregation in the C. elegans model. We were then able to directly assess the degree to which protein aggregation influences normal aging rates."

A GERMAN INTERVIEW WITH AUBREY DE GREY
Wednesday, April 27, 2011
http://www.fightaging.org/archives/2011/04/a-german-interview-with-aubrey-de-grey.php
A translated interview with SENS Foundation co-founder Aubrey de Grey: "I have identified seven types of damage [that cause aging]. In five cases we can repair the damage in my opinion, by replacing irreversibly damaged cells by stem cells, or when garbage accumulates, we will remove [it]. In two cases, we need to engage in gene therapy, for example, through new DNA counteract mutations in the mitochondria. ... We should intervene as little as possible in the metabolic pathways themselves. This is too complicated, we do not know enough yet about it. I prefer the regenerative approach, the repair and maintenance. It is [sufficient] to repair the damage after it occurred. In this way, we do not [need to] understand all the molecular details and how they come about. But we have to intervene before the problems get out of control. ... A simple example is the stiffening of the extracellular matrix - this is the fibrous scaffold between cells. The stiffening occurs because certain molecules network with each other. There is a principal [agent], a molecule called [glucosepane], which has the largest share of the networking and reinforcement. We must find a way to break up about two-thirds of them again. If we break these reinforcements, it would eliminate about half of the damage. ... I think the probability is about 50 percent, that all of these therapies in 25 years actually show the desired results. The average life span might then be [increased by] about 30 years."

A STABLE, SELF-RENEWING SUPPLY OF NEURAL STEM CELLS
Wednesday, April 27, 2011
http://www.fightaging.org/archives/2011/04/a-stable-self-renewing-supply-of-neural-stem-cells.php
News from the field of stem cell research: "researchers [report] a game-changing advance in stem cell science: the creation of long-term, self-renewing, primitive neural precursor cells from human embryonic stem cells (hESCs) that can be directed to become many types of neuron without increased risk of tumor formation. ... It means we can generate stable, renewable neural stem cells or downstream products quickly, in great quantities and in a clinical grade - millions in less than a week - that can be used for clinical trials and, eventually, for clinical treatments. Until now, that has not been possible. ... Human embryonic stem cells hold great promise in regenerative medicine due to their ability to become any kind of cell needed to repair and restore damaged tissues. But the potential of hESCs has been constrained by a number of practical problems, not least among them the difficulty of growing sufficient quantities of stable, usable cells and the risk that some of these cells might form tumors. ... [Researchers] added small molecules in a chemically defined culture condition that induces hESCs to become primitive neural precursor cells, but then halts the further differentiation process. ... And because it doesn't use any gene transfer technologies or exogenous cell products, there's minimal risk of introducing mutations or outside contamination."

A PRIZE FOR BRAIN PRESERVATION
Tuesday, April 26, 2011
http://www.fightaging.org/archives/2011/04/a-prize-for-brain-preservation.php
An article on uploading and preservation of the brain: "Ken Hayworth, a cognitive neuroscientist, has the difficult task of juggling two hats on his head, or should we say brain. With the first one, he and his colleagues at Harvard University are working on enhancing the power of an instrument that automates the mapping of brain tissues to answer a fundamental question that still faces neuroscience: How are the 100 billion neurons wired in the brain and how they know what function to perform? If you think that's difficult to digest, ponder over the bigger objective that Hayworth has on his mind - not as a Harvard post-doctoral student but as the president of The Brain Preservation Foundation: 'My personal long-term goal is to upload a human mind into a machine. I think it's the larger conclusion of neuroscience. This means, I can put a specific mind into a robot.' ... In the next five years, he is confident of seeing an entire human brain preserved chemically and embedded in plastic. This brain, he explains, can eventually be automatically cut into ultra-thin strips and scanned at very fast rates and high resolutions. With these maps, neuroscientists can figure out how the neurons are wired and how they create memories, skills and personalities. ... Hayworth is convinced that once the scientific and medical community understands that brain preservation techniques (cryonics or plastination) are successful in preserving 'high-quality brains', people will come around the idea eventually. He admits, though, that legal problems will remain (currently, one can't preserve a brain before a person is legally dead). Regardless, he has announced a prize of $106,000 to anyone who can preserve a large mammalian brain such that all the synaptic connections are intact using today's technology. Two major laboratories are competing for the prize, says Hayworth, adding: 'We have to image that brain and verify that claim ourselves. For this, we will need the help of labs and more money. Currently, I have zero money in the bank.' But he is optimistic that "this message will resonate. 'I have been talking to some very wealthy people (who do not want to disclose their identities currently). They believe in this and want to see credibility. Once people start seeing results in brain preservation, there will be more converts.'"

A NOVEL METHOD FOR POTENTIALLY RESTORING SIGHT
Tuesday, April 26, 2011
http://www.fightaging.org/archives/2011/04/a-novel-method-for-potentially-restoring-sight.php
An interesting technology demonstration noted at the Technology Review:: "Viruses can deliver light-sensitive proteins to specific cells in the retinas of blind mice, allowing rudimentary vision, according to new research. ... The new light-sensitive proteins were active for the length of the study, about 10 months, suggesting the treatment would work long-term. In addition, the therapy appeared safe; the proteins, which were derived from algae, remained within the eye, and they did not trigger inflammation. ... In my opinion, the biggest step forward in this paper is the use of viral delivery techniques, the same delivery techniques that would have to be used should the technique move on into human treatment. ... Recent gene-therapy studies, which used similar viruses to deliver different proteins, have shown preliminary success in treating a rare genetic form of blindness in patients.But the current approach could be applied to a much broader group of people because it could restore light-sensitivity to the retina regardless of the cause of degeneration. .. [Researchers] used a specially designed virus to deliver numerous copies of the gene that makes a protein called channelrhodopsin to the eye. The protein forms a channel that sits on a cell's membrane and opens when exposed to light. Positively charged ions then rush into the cell, triggering an electrical message that is transferred to other cells in the retina. The gene was modified so that it became active only in specific retinal cells called bipolar cells. In a healthy eye, these cells are activated when adjacent photoreceptor cells detect light. The researchers hope that making the bipolar cells directly responsive to light in an eye stricken by retinal degenerative diseases, such as retinitis pigmentosa or macular degeneration, could enable the altered cells to replace photoreceptors that have died off. "

AN UPDATE ON GADD45 RESEARCH
Monday, April 25, 2011
http://www.fightaging.org/archives/2011/04/an-update-on-gadd45-research.php
A Russian group has been investigating the effects of GADD45 on life span in flies, which I noted last year. Here is a post from one of the researchers outlining the present state of research: "As I wrote earlier, we were able to do while his most important discovery - show that activation of the GADD45 gene by genetic methods leads to longer life of fruit flies up to 80%. Our research also showed that in old age animals are not able to activate their own GADD45, which leads to deterioration of stress resistance and aging (article forthcoming). Transcription factor FOXO, which plays a role in anti-aging generally known (it provides the ability to handle stress, suppressed IGF-1 signaling), causes DNA repair through GADD45. GADD45 is controlled by another gene of longevity - SIRT1. We are now looking for investors to look for substances capable of restoring expression of the gene GADD45 in older individuals to the level inherent in the young. ... Ability of cells to maintain a high level of inducible GADD45 with age could be an excellent marker for longevity of the individual. To prove this, it is necessary to conduct a screening study among different age groups and centenarians." We will see a lot of this in the years ahead: the financial success achieved by researchers in the field of sirtuins, despite a lack of practical results, will attract a great many research groups to try to slow aging through metabolic manipulation. Unfortunately this is the long, hard path to a poor end goal: as a strategy for tackling aging it is a bad choice when compared to the Strategies for Engineered Negligible Senescence.

HORSES OBTAIN BETTER STEM CELL MEDICINE THAN HUMANS
Monday, April 25, 2011
http://www.fightaging.org/archives/2011/04/horses-obtain-better-stem-cell-medicine-than-humans.php
Thanks to the present restrictive state of medical regulation, horses have been getting better treatments than people for a few years now: "Take the case of SandSunSea, a 3-year-old colt by the late Pleasant Tap, bought for about $90,000 at a yearling sale in Canada. His trainer, Roger Attfield, elected not to try racing him at age 2. 'He was a horse that I gave time to because he was a big growing boy,' Attfield said. At 3, the colt was coming along nicely but then suffered a torn flexor tendon in his right front leg. 'He was just about ready to run when this happened.' ... Such an injury normally would take nine months to a year to recover from, and the horse might re-injure himself once he finally goes back into training. Attfield turned to stem-cell therapy. He shipped the horse from Payson Park training center in Florida to Woodford Equine Hospital in Versailles, where Dr. Joe Yocum removed a bit of the horse's tissue one morning in March. At the MediVet labs, which opened earlier this year in Nicholasville, 1.2 billion stem cells were pulled from 30 grams of fat taken from SandSunSea. ... That afternoon some of the cells were injected back into SandSunSea's leg. (The rest are stored frozen at the MediVet lab in case more treatments are needed one day.) The results surprised even Yocum, who is a partner in MediVet America, one of a handful of companies around the world that offer stem-cell therapy to veterinarians. 'I went back after two weeks and scanned him and could hardly even find the lesion. He looks perfect, really.' Normally it might take four months for the lesion to gradually disappear, he said. 'This thing was practically obliterated in two weeks.'"

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