SENS: Just Like the Rest of Science, But Not

The scientific method and the community of science that surrounds it is truly a powerful machine - able to take the worst aspects of human nature, sailing atop a river of garbage specked with half-wrong answers, and spin that mix into the gold of technology. It doesn't matter what your right to wrong to nonsense ratio is when it comes to deciphering the world; so long as you have the will to progress and your sifting mechanism is good enough, accumulating a whole pile of right is just a matter of time.

The front line of science is a messy place; a mostly wrong messy place, as any of us who have spent time there know. A recent study claimed massive error rates across all scientific papers - which is not a surprise to scientists. The closer to the edge of knowledge you come, the more wrong you'll find - a great frothing sea of wrong, enthusiastically generated by scientists in search of nuggets of right. It's all part of the process, and you have to step back from the details in order to see where the process is taking you. In any complex field, and biotechnology and medicine are about as complex is it gets outside astrophysics, validating truth takes time. Scratch any unanswered question and it'll bleed papers and reviews, a dozen for any given position on the topic.

So the odds are good that much of the present science of the Strategies for Engineered Negligible Senescence (SENS) - a mix of science, ethics and purpose aimed at advancing the development of real, working anti-aging therapies capable of repairing age-related damage and thus rejuvenating the frail and greatly extending healthy life spans - is flawed or wrong in many ways, just like the rest of modern biotechnology. No-one, least of all biomedical gerontologist Aubrey de Grey, is standing up to claim absolute truth - we're up there in the frothing sea of wrong, driven by purpose and the will to progress, as you'll recall. (Claims of absolute truth are a strong sign that you are dealing with a crank; crankery is the anti-science, the ungoverned impulse to sole certainty, the production of claims without verification or against verification). SENS science, like all frontline science, is the best foot forward, built on foundations that will be proven to be wrong, composed of details that will be shown to be mistaken, and provides plenty of point-by-point grist for scientists to argue about now, as even a cursory visit to the Immortality Institute SENS forum will demonstrate.

None of this is any different from any other upper branch of science. People thrive in it. It gets things done, it makes progress, it produces truth, knowledge, technology and better, longer lives - but only if the will is there. You see, there are differences between branches of science and facets of the scientific community, and those differences lie in what they see in themselves, in their own science. Do they have purpose? Are they looking to a specific future, with specific aims? The reason I see SENS as suitable vehicle to champion within the scientific community is not exemplary science; SENS is good science, but good science is going on all over the place. Rather, it is the surrounding package of ethics and goals, the deliberate statement of radical life extension and the defeat of age-related disease and degeneration as a worthy thing for scientists to attain. This is what differentiates SENS and those scientists who support it. The science will evolve, just as all good science evolves. Researchers learn new things, discard what doesn't work, filter out the right from all the wrong. It's the framework of will and goals that guides the work that matters, that carries the work forward. Gerontologists could work towards understand aging or they can attempt to cure aging - that's a big difference, and it's all in the framework.

So support SENS and associated initiatives such as the MPrize for anti-aging research - it'll make a big difference to your future, to all of our futures. Let's put the best foot forward when it comes to making our healthy lives far, far longer!

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Calorie Restriction On CBS

CBS News recently aired a segment on the practice of calorie restriction (CR) for healthy life extension: "Definitely his life expectancy is higher than an average American. ... Doctors like Fontana are conducting long-term studies of C.R. They're convinced it protects against major diseases. Dr. John Holloszy, principal investigator, agrees. 'There's no chance of them getting type 2 diabetes, they have very low blood pressure, and the risk of them developing cancer is markedly decreased.'" That said, I don't think their comments on exercise are helpful - exercise affects a range of metabolic processes over the long term in ways I cannot see diet choices replicating. It's perfectly possible to both practice CR and exercise moderately - you certainly should if you'd like to see as much as possible of the real anti-aging medicine of future decades!


Linking Obesity And Alzheimer's

It is known that obesity raises the risk of suffering Alzheimer's (as well as numerous other fatal age-related conditions); the open question is the biochemical mechanisms linking the two. One research team proposes the following: "They found a strong correlation between body mass index and high levels of beta-amyloid, the sticky protein substance that builds up in the Alzheimer's brain and is thought to play a major role in destroying nerve cells and in cognitive and behavioral problems associated with the disease. We looked at the levels of beta-amyloid and found a relationship between obesity and circulating amyloid. That's almost certainly why the risk for Alzheimer's is increased." Given that scientists are still arguing over the role of beta-amyloid in Alzheimer's, this is little too much certainty, but the mechanism is going to be something like this.


Aubrey de Grey and SENS in Blogs

Recent media attention given to biomedical gerontologist Aubrey de Grey and the Strategies for Engineered Negligible Senescence (SENS) has given rise to a couple of good blog posts in recent days, focused on the science of extending the healthy human life span. That in mind, I should take a moment to remind you all that de Grey will be appearing in a 60 Minutes segment on radical life extension this Sunday, January 1st. Methuselah Foundation Executive Director Kevin Perrott has more:

The high profile and much watched CBS investigative journal program, 60 minutes, will be highlighting the Mprize in a segment dedicated to the discussion of what the prospects for healthy life-extension.

It doesn't get much better than watching Morely Safer asking Mprize Founder Aubrey de Grey seriously what "he is talking about.." when it comes to longevity and hearing Dr. de Grey reply "indefinite" longevity... on international television... to an audience whose mean age is somewhere around 60.

Damn Interesting has a long interview with de Grey and Perrott in a post entitled "Zen and the Art of Human Maintenance." There's a lot in there, so read it all:

There is a disease which causes the human body and mind to gradually deteriorate, causing its sufferers to experience discomfort, memory loss, failed health, disfigurement, and severe physical and mental handicaps. It is always fatal, and there is no known cure. The scientific term for this disease is Senescence, though it is more commonly known as aging or growing old. Every single person is born with this condition, and it kills over a million people a year in the U.S. alone.

Thinking of old age as a curable disease seems strange to some people, but great leaps in medical progress over the past few decades are indicating a future where no one will need to suffer the deteriorating physical condition and the dulling of the mind which occur during aging. Scientists may be able to repair this flaw in evolution's design, and perhaps perpetual youth will become a reality soon enough that you and I might live to enjoy it.

To round off, here is a thoughtful and satisfying post from a blogger new to the concepts of SENS and radical life extension:

Could science offer us immortality one day? How about to those of us already living? Seems too good to be true, but then I'll bet so did cell phones in 1900.

Again, read it all. Good stuff - we advocates have to work harder to get the message out to the hundreds of thousands of other folk who think the same way.

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60 Minutes On Radical Life Extension

Biomedical gerontologist Aubrey de Grey - advocate for the Strategies for Engineered Negligible Senescence, a path towards and justification for real anti-aging medicine - Jay Olshansky and other scientists will be appearing on 60 Minutes on Sunday, January 1st in a segment on radical life extension: "60 Minutes is planning three stories about beginning anew this New Year's Day. ... We'll also take a look at new medical research that may lead to people living much longer lives than we ever thought possible, maybe even 400 or 500 years. Some doctors believe with medical breakthroughs on the horizon, humans can live much longer lives." Advocates and interested parties are discussing matters over at the Immortality Institute; you'll find links to the teaser video there too. A great opening for public awareness of healthy life extension science and the efforts of the Methuselah Foundation in 2006!


Not So Optimistic About the "Anti-Aging" Marketplace

Glenn Reynolds made the following comment a few days ago in a post on Ray Kurzweil, the Singularity and healthy life extension:

Meanwhile, here's evidence that a lot of people want to see progress in aging research: "Forget '40 is the new 30.' Now even twentysomethings are joining the quest for eternal youth by using anti-aging products and wrinkle treatments." Think how big the market will be when the products actually work.

I don't think that this is the psychology at work here - people don't associate "anti-aging" the cosmetics branding to longevity research or scientific efforts to actually hold back the aging process. It's not even the same association as "anti-aging" the health brand. In the cosmetics case, people say "anti-aging" and hear "high class, better looking" and in the health case they hear "healthier." Just because the branding contains the words "anti" and "aging" does not mean that people actually think of either of those terms in a way that includes their stand-alone meanings.

One might say that my own life is something of a laboratory for studying the way in which people overload a word. Know me for long enough and your brain will carve out a whole new association for the word "Reason" - without you being all that aware of it until it is pointed out. That new association is pure name, with none of the meaning of the original word. The same thing happens with brands.

If there really was a significant spill-over of sentiment and support from consumers of "anti-aging" brands to meaningful, scientific anti-aging research - or even between different "anti-aging" brands in the marketplace - I don't think we'd be seeing quite the same sort of hostile confrontation between brand-holders and scientists as takes place today. More to the point, I suspect that volunteer organizations like the Methuselah Foundation would be having far less of an uphill struggle than has been the case to attain their present level of success, and scientists backing rapid progress towards working anti-aging therapies would not be struggling to raise large-scale funding and fight conservatism within their ranks.

Looking back at the past two decades, the pro-healthy life extension communities of the time built up a very effective distribution mechanism, but failed to overcome the very same hurdles we struggle with today: how to generate widespread public support for healthy life extension and direct large-scale funding into meaningful anti-aging and longevity research. So now we see the distribution mechanism spinning its wheels on branding, while the present generation must address the same problems: how do we develop useful anti-aging technologies in time for us to benefit?

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Stem Cells At The Root Of Regeneration

Given that regeneration is driven by stem cells, it would make sense to look for changes in stem cell activity underlying known methods for improving natural healing processes. Here, via Medical News Today, news that this is the case for hyperbaric oxygen treatments: "a typical course of hyperbaric oxygen treatments increases by eight-fold the number of stem cells circulating in a patient's body. ... We reproduced the observations from humans in animals in order to identify the mechanism for the hyperbaric oxygen effect. We found that hyperbaric oxygen mobilizes stem/progenitor cells because it increases synthesis of a molecule called nitric oxide in the bone marrow. This synthesis is thought to trigger enzymes that mediate stem/progenitor cell release." This would seem to open the door on a number of possible ways to greatly amplify existing healing processes.


Calorie Restriction, Sirt1, Insulin

PLoS Biology brings us more interesting calorie restriction (CR) science - relationships between Sirt1 (the mammalian version of Sir2) and insulin in this case: "Sir2 and insulin/IGF-1 are the major pathways that impinge upon aging in lower organisms. In [roundworms] a possible genetic link between Sir2 and the insulin/IGF-1 pathway has been reported. Here we investigate such a link in mammals. We show that Sirt1 positively regulates insulin secretion in pancreatic [beta] cells. ... In mammals a characteristic set of physiological changes takes place during long-term CR, which overlaps the rapid physiological adaptations to short-term food limitation. One such change is the use of dietary fat or fat mobilized from [white adipose tissue] for energy [4]. Another is a large reduction in blood insulin levels accompanied by an increase in insulin sensitivity, i.e., the ability of insulin to promote glucose utilization."


Aging, Death, Nanotechnology

Mike Treder is discussing some of our favorite subjects over at Responsible Nanotechnology:

Among the most intriguing research of our time is the effort to understand the process of aging, and perhaps to arrest or even reverse its effects.


Genetic therapy holds great promise for treating several serious health problems, as well as possibly stopping natural deterioration altogether. However, the current state of the art can also cause problems, including cancer. Eventually, with the use of advanced nanotechnology, scientists may be able to directly edit the DNA of living cells in the body.


Health improvement and life extension do not depend on [molecular manufacturing], but it certainly will make them accessible to more people. Any treatment that can be automated can be applied to any number of people at low cost; such efficient research will speed the development of cures for complex problems such as aging.

Go and read the rest of it. It's worth noting that biomedical gerontologist Aubrey de Grey's SENS writings make it clear that you can't gene engineer away all the problems, just like you can't regenerate away all the problems using stem cell medicine - even if you did as much as is theoretically possible, you'd still be left with the buildup of waste products in and around cells leading to age-related disease and death. (Hence the need for LysoSENS research, which you can presently support in a number of ways).

Much of the groundwork technology needed for the future of real anti-aging medicine in the near future will be accomplished as incidental progress required for goal-driven research. For example, scientists have been driven by AIDS research to learn a great deal about the biochemistry and genetics of the immune system - because this knowledge was necessary in order to produce viable anti-HIV strategies. Cancer research has led to a vast expansion in our knowledge of cellular biochemistry - and how it relates to cell aging - as a necessary part of progress in that field. I believe that the useful byproduct of nanotechnology research will be complexity management - although one could make the case that nanotechnology will be the field benefiting from the complexity management technologies developed in order to move forward in biotechnology. Either way, we must make leaps and bounds in our ability to interact with, understand and control enormously complex systems if the future of medicine is to be even close to the most optimistic predictions.

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Plausible, Robust Old Age

The plausibility of good lifestyle choices leading you into a robust old age - judged by the medical technology and possibilities of today - makes a big difference when looking at the future. The length of your healthy life in the long term is far more dependent on future anti-aging medicine than anything else - how effective it is, how fast it is developed, how much you supported research - but reaching the era of working anti-aging medicine while still being healthy enough to benefit is a matter of working with what you have now, using the health tools of today. Here, the Deseret News notes a study that suggests reaching your mid-80s in good health, using the technology of the past 50 years, is perfect plausible for most people. You can do the math based on your age and the predictions of futurists to see where this might get you.


The Roots Of Type 2 Diabetes

(From EurekAlert). Researchers are digging into the biochemical roots of type 2 (age-related) diabetes: "knocking out a single gene encoding the enzyme GnT-4a glycosyltransferase (GnT-4a ) disrupts insulin production. ... a high-fat diet suppresses the activity of GnT-4a and leads to type 2 diabetes due to failure of the pancreatic beta cells ... In its earliest phases, the disease causes failure of insulin-secreting beta cells in the pancreas, which leads to elevated blood glucose levels. As the disease progresses, the insulin-secreting beta cells overcompensate for the elevated blood glucose, and eventually pump out too much insulin. This leads to insulin resistance and full-blown type 2 diabetes. The new studies suggest that people with an inherited predisposition to type 2 diabetes might have variations in the gene for GnT-4a." The simple solution is, of course, appropriate diet and lifestyle choices.


A Positive Look At Cancer Research

The New York Times is printing an optimistic article on the state of cancer research: "For the first time, we have the tools needed to attack the problem... We're close to being able to put our arms around the whole cancer problem. We've completed the list of all cancer cells needed to create a malignancy, and I wouldn't have said that five years ago. ... It's starting to come into focus how one might target the problem. Individual cancers are going to fall one by one by targeting the molecular abnormalities that underlie them. ... Seeing cancer become more like what has happened with AIDS would not be shocking. Does that mean cure? Not necessarily. We may see patients treated until they die of something else." Cancer, like neurodegeneration, results from age-related cellular damage that must be repaired or prevented if we are to greatly extend the healthy human life span.


An Interesting New Blog

I'm always pleased to see more people blogging on the advancing science of healthy life extension - biotechnology, nanotechnology, understanding our cells and biochemical processes, defeating age-related disease, patient and research advocacy ... the works. There's only so much one person can usefully do in any endeavor, advocacy included - but many people can accomplish great things. This latest newcomer is the author of the Biosingularity blog:

I am an Associate Professor of Microbiology and Immunology at a medical school in United States. My research interests are human immune system, HIV infection, stem cells and reprogramming differentiation programs of cells.


The convergence of biology with nanotechnology and information technologies will soon create an unprecendent ability to understand and manipulate biological systems. I have coined the term Biosingularity to define a time when we will be able to engineer new biological systems and have complete molecular control in manipulating existing life forms.

As we we approach biosingularity, we will first eliminate all diseases, then slow and eventually stop aging. At biosingularity we will be able reverse the aging process and amplify human intelligence and capabilities beyond unimaginable levels.

I started this blog to chronicle the remarkable advances in biological systems and hopefully also to provide a conceptual framework to discuss reverse engineering biological systems and its profound ramifications for the future of humanity.

Biosingularity has been a useful, quality effort to date, providing another good transhumanist slant on progress in modern biotechnology; you should certainly check it out.

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Support For Reliability Theory

A study reported at EurekAlert gives the expected support for the reliability theory of aging: "Records from four European countries show that, on average, survivors of generations with rampant childhood infection - measured by cohort mortality rates at young ages - were shorter and died sooner than counterparts from generations with less childhood disease. Crimmins and Finch propose that even when they grew into apparently healthy adults, survivors of high-infection generations carried a heavier lifetime burden of inflammation. This in turn accelerated the progress of cardiovascular disease. ... Our model implies that the reduction in lifelong levels of infections and inflammation reduced and delayed the progression of cardiovascular disease and mortality due to heart disease."


Program For 35th AGE Annual Meeting

The program for the 35th annual meeting of the American Aging Association (AGE) - to be held in early June 2006 in Boston - is already long and interesting, even at this early date. As for the 2005 annual meeting, research into calorie restriction, metabolism and longevity is much in evidence. AGE is representative of the mainstream of pro-healthy life extension but conservative gerontology, as demonstrated in the mission statement: "To promote biomedical aging studies directed towards increasing the functional life span of humans with one goal being to slow the aging process. To keep the public informed of the progress of aging research and of practical means of achieving a long and healthy life."


The Cruelty of "Ethics"

How low modern medical ethics and bioethics has sunk; once upon a time it was a necessary, noble part of the medical profession - now it chiefly exists to cause suffering, block freedom of research and slow progress ... all the while paying fat salaries to those tasked with finding ever more "problems" where none exist. A good example of this cruelty can be found in a recent Scotsman article on new stem cell research for neurodegenerative diseases: how is it in any way ethical, right or moral to prevent the terminally ill from making their own informed choice to participate in research and trials of new therapies, to prevent them from seeking a possible cure? Medical "ethics" has truly become a despicable profession.


The Benefits of Editing DNA

A great deal of good medicine could be accomplished if we just had the option of adjusting our DNA - safely making small edits on an ongoing basis to genes and their expression in specific tissues. Shifting the controlling genetics of your metabolism into the most optimal configuration for healthy life span, based on what is learned from calorie restriction studies and other research, would be one of many options. Sorting out some of the known problems in the aging immune system would be another. There are many more opportunities for improvement along the same lines, but the full genetics of aging are far from clear. Studies performed to date show that many genes - hundreds for any given organ in the body - change their function as life progresses, but it is not known how much of this is relevant or interesting, programmed aging, a reaction to age-related cellular damage - or the direct result of age-related mutational damage to DNA. Even in this last case there are still ways forward based on the alteration of DNA: editing can be a method for repairing damaged DNA as well.

Scientists are in the early stages of writing changes to DNA; tools such as viral gene therapy and protofection are blunt hammers in comparison to the state of the art yet to come, and even these are still in trials and the laboratory. Matters are advancing rapidly, however, as recent news illustrates:

Sickle cell disease corrected:

In a study to be published in the January 2006 issue of Nature Biotechnology, researchers led by a team of scientists at Memorial Sloan-Kettering Cancer Center have devised a novel strategy that uses stem cell-based gene therapy and RNA interference to genetically reverse sickle cell disease (SCD) in human cells.

Editing DNA to disrupt HIV:

Sangamo BioSciences Inc. said its technology for "editing" DNA has allowed it to develop a new therapy that can make cells resistant to HIV infection. The technology disrupts the so-called CCR5 gene that provides an entryway for HIV into T-cells, the infection fighting cells of the immune system.

On/off switch for gene therapy:

A new method has been developed for switching genes on and off that could greatly improve gene therapy. ... Until now, researchers working to develop successful gene therapy for diseases such as Parkinson's have hit roadblocks such as toxic side-effects from over-expression of the therapeutic gene, and adverse events caused by immune system reactions to the viral delivery systems currently used to deliver the therapeutic genes. Now, we've engineered a genetic switch in a novel gene transfer vector that will overcome those barriers and set the stage to allow the next phase of research to occur

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Understanding Neural Regeneration

From John Hopkins Medicine, welcome news of continuing progress towards a complete understanding of brain biochemistry: scientists "have discovered the steps required to integrate new neurons into the brain's existing operations. For more than a century, scientists thought the adult brain could only lose nerve cells, not gain them, but in fact, new neurons do form during adulthood in all mammals, including humans, and become a working part of the adult brain in mice at the very least. ... We've shown that [the neurotransmitter] GABA instead excites new neurons and that this is the first step toward their integration into the adult brain. ... their discovery might help efforts to increase neuron regeneration in the brain or to make transplanted stem cells form connections more efficiently." A very effective regenerative toolkit for the brain is a requirement for living far longer than we do now.


Comments on "The Long Tomorrow"

I have not yet found the time to read evolutionary biologist Michael Rose's "The Long Tomorrow" - my reading list is backed up by years even in the slowest of work months, sad to say.

The conquest of aging is now within our grasp. It hasn't arrived yet, writes Michael R. Rose, but a scientific juggernaut has started rolling and is picking up speed. A long tomorrow is coming. In The Long Tomorrow, Rose offers us a delightfully written account of the modern science of aging, spiced with intriguing stories of his own career and leavened with the author's engaging sense of humor and rare ability to make contemporary research understandable to nonscientists.

My commentary to date has been limited to "here it is, check it out" and a reminder that you'll find more of Rose's writing in the first Immortality Institute book of essays. Fortunately, there are always others who will take up the slack; Ben Goertzel offers a few words, for example (you may have to scroll down to find the post, depending on your browser):

The book is easy to read by anyone who understands high school biology, yet presents and describes important research without significant dumbing-down. It also does a pretty good job of getting across the flavor of modern experimental biology research ... and of emphasizing the point that a lot more progress toward curing aging could be made if society chose to devote resources toward this goal. Many very good scientists, such as Rose himself and Aubrey de Grey and many others, have promising ideas regarding how to better understand and potentially alleviate the aging process, but our society is more interested in spending money blowing people up and inventing new forms of fabric softener. Bummer, huh.

Goertzel goes on to give just one example - from personal knowledge - of the many, many aging research projects that could be undertaken immediately if the funding materialized. Funding, of course, never just materializes; any sort of large-scale funding for medical science is the end result of a long process of public support, patient advocacy, activism, education, preliminary work, advocacy within the scientific community, and so forth. It's a great deal of work, and we're still in the earliest stages when it comes to drumming up funding for research aimed directly at extending the healthy human life span.

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On/Off Mechanism For Gene Therapy

(Via Betterhumans). Some of the most promising new research into cures for age-related conditions is based on gene therapy; editing cellular behavior by changing genes. So it is good to see that scientists are progressing rapidly towards increasingly sophisticated - and thus safer, and more effective - gene therapy technologies: "A new method has been developed for switching genes on and off that could greatly improve gene therapy. ... Until now, researchers working to develop successful gene therapy for diseases such as Parkinson's have hit roadblocks such as toxic side-effects from over-expression of the therapeutic gene, and adverse events caused by immune system reactions to the viral delivery systems currently used to deliver the therapeutic genes. Now, we've engineered a genetic switch in a novel gene transfer vector that will overcome those barriers and set the stage to allow the next phase of research to occur."


A Puppet Show of Grotesques

From my minarchist, Austrian perspective, the activities in and around Washington DC comprise a puppet show of grotesques - a distorted mockery of reality. Yet this show is taken at face value by all too many people; when that dangerous mix of dream logic, greed, ignorance and lies governs the real world, terrible damage is done. Take the recent sideshow that was the White House Conference on Aging as one small part of the whole, for example. Here we have representatives of a hundred fronts of the culture of entitlement, grubbing and manipulating for short-term gain in ignorance and greed, all the while hurting their own long term prospects by supporting socialism in medicine and other failing centralization strategies. More vitally, we are presented with a supposedly important event on a major problem - the problem of age-related frailty - that fails to meaningfully address any plausible solution.

Not that we should be surprised. Plausible solutions and their enactment are the province of the free market and people who work to create and build - something that policians cannot do. The only results you'll obtain from the insertion of big government and central control into any arena of human endeavor are shoddy goods, higher costs, and slow progress. One would hope that most people understand what happens when you attempt to centrally control complex systems - the fate of those who lived through the Soviet Union should spring to mind. As centralization grows, progress, efficiency and quality die; this is an iron law of our time, and one that - sadly - seems to have to be relearned again and again.

If you want to assist the elderly, the best way forward is to support directed medical research towards real anti-aging medicine capable of repairing and preventing age-related cellular damage, the source of all age-related disease, degeneration and death. With this technology, the presently frail elderly would be healthy, wealthier and more experienced than you or I, and in no need of assistance. In the political arena, the best support that can be given to medical research is exactly the same as the best support that can be given to any human activity: it is the support of no regulation, no taxes, no government beyond the rule of law and property rights, individual advocacy, persuasion and hard work.

What goes on in Washington DC would be darkly funny if it wasn't going to contribute to to hundreds of millions of unnecessary, avoidable, preventable deaths due to aging in the years ahead. Simply persuading people to support healthy life extension research is enough of a challenge; the destructive arrogance of politicians - and the destructive greed and ignorance of people who have never needed to learn responsibility - threaten the future of our health and longevity through their effect on the pace and capabilities of medical science.

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Advancing Scaffold Technology

(From Innovations Report). The use of biodegradable, often nanoscale-engineered, scaffolds spreading in tissue engineering circles, and a large future market for this technology seems certain. So it is that materials scientists have a strong incentive - sources of funding - to develop better scaffolds: "Flock technology for example is applied in an industrial scale to the production of the velvety surfaces of spectacle-cases. Now, this method shall help to produce new types of medical implants. In order to create resorbable scaffolds, membranes made of mineralised collagen are covered with a gelatine-based biocompatible glue. In the next step, biologically degradable fibres are flocked on the tapes. ... This way a kind of 'velvet structure' is created on which cells can be seeded with a high density."


A Glance At Private Stem Cell Funding

Private and venture funds are flowing for at least some areas of stem cell research; successful hybrids of new stem cell technology and old-style drug development pipelines seem to be doing well: "Osiris Therapeutics, Inc. announced that it has closed a $19 million private equity round. The money will fund the company’s five ongoing clinical trial programs using their proprietary adult stem cell technology platform. The round was arranged by Swiss investment firm Friedli Corporate Finance, Inc. In total, the company has raised $70 million in 2005." Elsewhere, Advanced Cell Technology, long the poster child for the detrimental effects of threatened anti-research legislation on private funding, has emerged from the long dry spell in the past year.


Aging Research in Canada

Here are a couple of items and commentary on the mainstream study of aging and longevity, linked by the common theme of Canada:

Canadian life expectancy rising:

According to a new Statistics Canada report, the average life expectancy hit 79.9 years in 2003, up from 79.7 in 2002. ... In the past quarter century, the difference in life expectancy between the sexes has narrowed. Men improved by 6 years, or one year for every four calendar years since 1979, while women only improved by 3.6 years, or one year for every 6.7 calendar years.

On the forthcoming Canadian Longitudinal Study on Aging:

Which finally brings us to the Canadian Longitudinal Study on Aging (CLSA), which begins in 2008 and will track 50,000 40+ year old Canadians for 20 years. At this point it's not clear exactly what info they will be collecting and publishing (nutrition is mentioned, but how about suppliments like multivitamins?) but I expect the results to be fascinating and important non-the-less. It will be more than worth following over the years - and I'm young enough that the study will lead me rather than lag me :-). A read of their Executive Summary (a bit of a mis-nomer, since it's about 20 pages long) shows that they are on top of the game, even in terms of biotech/genetics/SENS type understanding of aging.

Watching life expectancy and the actuarial study of aging is interesting and useful in its own way, but it doesn't say all that much about the future of medicine - certainly not whether, and by how much, that medicine will extend our healthy life spans. People who carefully watch advancing research and capabilities suspect that actuarial forecasts based on extending trendlines in life expectancy - such as those used to justify or attack soon-to-be-redundant government pension schemes and forced retirement policies - are way out of line with what is likely. A trend is only a trend if it continues to continue, and examining the past is a terrible way to predict the future. Rather than wondering about it all, far better to put your shoulder to the wheel and help bring about real anti-aging medicine that much faster.

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The Dance Of Interacting Processes

(From the Bristol Press). A look at early stage research into one gene associated with aging shows what scientists have to go through into order to obtain even the smallest insights: "The gene, called 'lineage defective 4,' or lin-4, encodes a small piece of RNA ... worms lacking the lin-4 gene died prematurely. Extra copies of lin-4 led to shorter lives. Worms with mutated, less effective insulin receptors and mutated lin-4 lived a normal lifespan. C. elegans with normal lin-4 and mutated insulin receptors lived twice as long as normal. This finding suggests that lin-4 influences lifespan through the insulin signaling system ... It also explains why worms, rats and mice placed on low-calorie diets tended to live longer ... Less insulin means less protein synthesis and lower production of damaging chemical by-products ... If humans could somehow gear up their lin-4 genes and make extra [microRNA] to turn down insulin signaling, they might be able to delay aging."


Stem Cell Research In India

DNA Mumbai takes a glancing look at stem cell research in India: "There are about 15 laboratories across India in cities like Hyderabad, Pune, Bangalore, Delhi and Mumbai engaged in stem cell research and clinical applications. ... The LV Prasad Eye Institute in Hyderabad has been working with stem cells since 2001. 'We have been using limbal stem cells from the eye to treat damaged corneas and have had 70 per cent success in treating over 250 cases' ... In a recent experiment, the Delhi-based All India Medical Institute of Medical Sciences injected stem cells derived from bone marrow into 35 cardiac patients ... The patients were brought in at a critical stage when they were beyond bypass surgery and could have survived only with a transplant ... Sixty-four per cent showed improvement over 18 months."


Jason Pontin on Calorie Restriction

Jason Pontin's encounter with MPrize volunteers and Three Hundred members at the recent Methuselah Foundation dinner he was kind enough to host has resulted in this short article on calorie restriction at the MIT Technology Review:

A small number of people restrict their caloric intake in pursuit of longer life. So what do they eat for the holidays?


In the mid-1990s, Leonard Guarente, a molecular biologist at MIT, discovered a gene in yeast and worms (called SIR-2) that responds to caloric restriction by producing an enzyme that shuts down long stretches of DNA involved with metabolism and aging.

Today, a small number of people try to trigger the therapeutic benefits of SIR-2 by practicing caloric restriction with optimal nutrition, CRON, or more simply, CR.

Not quite correct on the science; I think it's jumping the gun to claim that researchers know exactly how calorie restriction works at this stage. Overall a fairly positive piece, however, which should please other advocates at the CR Society.

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Embryonic Stem Cells, As Is

Injection of unprepared embryonic stem cells into the body sounds like a good way to generate cancers rather than regeneration, but why not try it in animal models? From Betterhumans: "Injecting embryo stem cells 'straight up' - without changing their cell type first - has fixed damage in an animal model of heart attack. ... the stem cells, when transplanted into damaged mouse hearts, morph into functional forms of cells that compose a healthy heart. The study is considered important because it means that blank-slate embryonic stem cells could be introduced directly to damaged heart tissue to repair heart muscle and blood vessels. ... One intriguing result of the new study is that the implanted cells did not result in tumor formation, one of the primary safety concerns for stem cell therapy."


Researching Telomere Length

From EurekAlert, a look at one way in which telomeres, stem cells and long term health and longevity are tied together: "In this family, the affected grandmother developed gray hair in her 20s and lung problems in her early 60s and died at age 65. Her affected children developed signs of the disease about 10 years earlier than she had, and analysis of their cells revealed that 60 percent to 75 percent of their chromosomes had dangerously short telomeres. ... We know it only takes one critically short telomere to make a cell die, so it's clear that the more really short telomeres a person has the faster problems will develop. ... We thought there might be some relationship between telomerase, telomere length and the survival of stem cells, but it was really exciting to see it."


Foresight Nanotech Institute $40,000 Challenge Grant

Continuing the theme of end of year donations to favored transhumanist, pro-technology and healthy life extension causes, I should point you all to the $40,000 challenge grant over at the Foresight Nanotech Institute:

Thanks to a generous $40,000 Challenge Grant, every donation you give to Foresight is matched dollar for dollar up to this amount. This Challenge is for a limited time only. Please give now and together we can build an exciting future.


Donations received by Foresight between now and December 31, 2005, qualify as a 2005 tax deduction to the full extent permitted by U.S. law. For extra tax savings, you may also donate appreciated stock and avoid capital gains.


Donate by mail -- checks postmarked by January 31, 2006 (Dec. 31 for 2005 deductions) are also eligible for matching funds.

The Foresight Nanotech Institute's work encompasses advocacy for the development of advanced nanomedicine - a path towards radical life extension and the postponement of aging. Foresight is also an organizational member of the The Three Hundred, donating to the MPrize for anti-aging research.

If you are interested in finding out more about nanomedicine and healthy life extension, you should start with a recent interview with nanotechnology researcher and radical life extension advocate Robert A. Freitas. Another good resource is the Chris Phoenix article entitled Nanotechnology and Life Extension. Get reading!

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Seen From A Distance, Through A Hedgerow

Via the Scripps Howard News Service, another great example of how the healthy life extension movement looks to those unfamiliar with the details - or to lazy journalists who can't be bothered to do a little fact checking with the subjects of their article. Still, it's a mainstream press piece on the prospects for radical life extension, complete with links to the Strategies for Engineered Negligible Senescence and the MPrize for anti-aging research: "The first person to live to age 1,000 probably will turn 60 in 2006. Within 20 years or so, we'll have treatments for aging. Medicine will repair the damage that already has occurred in people who are in their 80s. They'll live on and on with healthy bodies and sharp minds. Medicine also will keep younger people from aging and getting frail and decrepit." These aggressive timelines are dependent on massive funding - something that in and of itself will take a decade or two to create.


Metabolic Rate Or Metabolic Stability?

From PubMed, an interesting paper on aging and metabolism: "The modern version of [the 'rate of living'] theory is that duration of life is influenced by the relative speed of a species' resting metabolism. However, empirical evidence does not consistently support this hypothesis. ... For example, if the metabolic rate/oxidative stress theory is correct, efforts to intervene in the aging process should be directed at finding ways to reduce metabolic rate, lessen the production of reactive oxygen species (ROS), improve antioxidant defenses, or increase the quantity of antioxidants. If the metabolic stability hypothesis is correct, efforts to intervene in the aging process should be directed at finding ways to increase the stability of the steady state values of ROS, increase the robustness of metabolic networks, or improve the stability of antioxidant enzymes." Which is all about slowing the rate rather than addressing age-related damage directly, of course.


Reminder: Help Real Anti-Aging Research By Sending in Soil Samples

Researcher John Schloendorn is still looking for soil samples from around the world to screen for useful bacterial enzymes as a part of his work on LysoSENS research. He, and other researchers, are looking for enzymes that can break down age-related by-products that accumulate in and around cells, leading to a range of age-related conditions and general loss of function. If scientists can find a safe way to break down these damaging by-products - such as by using engineered bacterial enzymes - then they will have found a way to repair and prevent one part of age-related degeneration.

Schloendorn has received some samples in the past few weeks, but could still be working on more:

Just a brief status update -- we gratefully acknowledge the receipt of a small number of donated samples and they are now shaking in 7KC cultures, which are being monitored for bacterial growth and 7KC degradation every other day. It is too early to tell the result though.

It is now clear that we can scale these processes up much more, so you still have the chance to contribute the unique microbial ecology of your area. Without your help, there is no way we could ever incorporate your local bacterial strains in this project. So please continue to send us samples, they will be most gratefully received at any time during the next couple of months. If we find something you all will get proper credit in a publication and in fact I would love to demonstrate to the science world just how great the public support for SENS projects is with a long list of soil donors. So everyone who has not done so, please do contribute.

This is a simple way for all of us to get out of the house and do a little good for the future of meaningful anti-aging science. The more diverse a set of soil samples, the better, so get going!

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A Utilitiarian View

A pro-government - meaning unrealistic on the true costs of socialism and regulation - but utilitiarian view of the cost of health and value of longevity can be found at the NCPA website: "The reduction in mortality from 1970 to 2000 had an economic value of about $3.2 trillion per year. Over the longer term, the cumulative longevity gains during the twentieth century were worth about $1.3 million per person. ... advances against one disease, like heart disease, raise the value of progress against other age-related ailments, such as cancer ... reductions in mortality since 1970 have raised the value of further health progress by about 18 percent. The authors also suggest that current funding of medical research is too low. A single percent reduction in mortality from cancer or heart disease would be worth nearly $500 billion to current and future Americans."


Investigating Free Radicals

Kevin Perrott comments on recent investigations into the free radical theory of aging: "Some focused research using mice who exhibited premature aging was published recently in PNAS where reactive oxygen species [ROS] were suprisingly NOT implicated as a potential cause. Rather than supporting the widespread notion that the damage caused by free radical production in mitochondria leads to spiraling reactive oxygen species and more damage, eventually producing the symptoms of aging, the study upsets it." Needless to say, there is debate and disagreement: "He contends that the researchers didn't observe ROS buildup in the mutators because they checked the wrong cell types. Energy-guzzlers such as the nervous system and muscles incur the most harm from mitochondrial faults, he says, and researchers should scrutinize their cells, not connective tissue cells."


A Few Other Transhumanist Advocacy Non-Profits

The Methuselah Foundation is just one of a number of transhumanist non-profit advocacy groups formed over the past couple of years - it just happens to be the one I mention most often. These collaborative ventures can be viewed as the natural consequence of a narrowing between mainstream ideas and the concepts discussed in the earliest online transhumanist salons in the 90s. Prior to the internet, the cost of collaboration, distribution of information and acquisition of new members was high. With the advent of the internet, distributed transhumanist and futurist groups formed; ideas and positions were formulated and debated. Non-profit organizations require a certain level of public understanding and support for their cause, however. Lacking that easily available support, building these organizations is a tough job. Fortunately, the bootstrapping cycle of debate, propagation of ideas and raising support - so as to build organizations capable of propagating ideas and raising support - is moving into easier territory. The mainstream of ideas is finally catching up to the more moderate futurist concepts of the late 80s and early 90s. A number of small nonprofits - former labors of love - are expanding into larger, more professional, successful ventures, and new organizations are sprouting.

The Singularity Institute - an organization focused on advocacy relating to the development of general artificial intelligence, a very transhumanist goal - seems to be doing very well of late, for example. Hard work over the past year lies behind the headlines, of course, but I submit that the very same hard work ten years ago wouldn't have resulted in anywhere near the same level of success.

The Immortality Institute, like the Methuselah Foundation, is a volunteer organization that aims to advance healthy life extension - but there are few similarities beyond that. Diversity is a good thing! The Imminst volunteers have to be doing something right, as the Institute website now plays host to one of the largest online transhumanist communities. All-volunteer community initiatives include a book, film and, recently, the first Institute conference.

The Center for Responsible Nanotechnology looks, I imagine, much like the Foresight Nanotech Institute would look if it had been formed two years ago rather than two decades ago. Even the influential Foresight Institute has grown over the past couple of years as the mainstream discovered and discussed nanotechnology and nanomedicine. Much of the growth I'm pointing to in this post is a matter of riding the wave - even for those groups (such as Foresight) who were the ones out there working hard to make the wave in the first place.

The wave - the critical mass of discussion, understanding and resulting support for action - has not yet arrived for healthy life extension and directed research into ending age-related degeneration. But it's near, and coming closer because of the hard work of advocates and activists.

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Progress Using Follicle Stem Cells

(Via Genetic Engineering News). Scientists discovered a population of multipotent stem cells in adult hair follicles back in 2004, and now these cells are bring put to work in regenerative medicine: researchers "have found that stem cells from hair follicles of mice can be used to rejoin severed nerves in mouse models. Easily accessible hair follicle stem cells, which normally function to form the hair follicle which in turn form the growing hair in all mammals including man, have been shown to have great potential to produce nerve cells and many other types of cells. The hair follicle stem cells were used by the AntiCancer researchers to rejoin nerves in the legs of mice that were experimentally severed. After injection of the hair follicle stem cells, the nerves were rejoined and were able to regain function, enabling the mice to walk normally again."


Microarrys To Genes To Mechanism

From EurekAlert, a demonstration of the power of bioinformatics to speed medical research into age-related conditions. We already know that scientists can now move very rapidly to identify biochemical processes that cause disease if they just know which genes to use as a starting point. The hard part is finding those genes - but that is getting easier with the application of nanoscale engineering and computing power: "Microarrays are laboratory chips able to pick out which genes are active when different processes are occurring in the brain. When they analysed brains from people with Parkinson's, they found that out of all 25,000 human genes, regulation of 570 was highly abnormal in Parkinson's brains compared with non-diseased brains. This is the first study on Parkinson's disease where all human genes were studied."


Choose the MPrize For Anti-Aging Research as Your Year-End Charitable Cause

2005 is coming to a close, and what a year it was for the Methuselah Foundation and the MPrize for anti-aging research! It has been wonderful to see so much progress in awareness and action for healthy life extension and in support of directed research into repairing age-related cellular damage. You can help us finish 2005 on a high note by choosing the Methuselah Foundation for your end of year charitable donations. When you donate to support the Longevity and Rejuvenation prizes or LysoSENS research, your dollars are swelling the most effective method for making the public and scientific community to sit up and take notice. Working therapies for age-related degeneration could be realized within our lifetime - but only if we help to make it happen!

A look back at some of the highlights from the Fight Aging! archives shows just how far the Methuselah Foundation has come in the past 12 months:

January 18 2005 - Funding for Methuselah Foundation volunteers:

Aubrey de Grey, Chairman of the Methuselah Foundation, announced that recent generous sponsorship donations would enable two people committed to the extension of healthy lifespans to dedicate all of their time and energy toward furthering the mission of the Methuselah Foundation.

March 08 2005 - Hitting the magic $1 million in pledges:

As you may have noticed, Aubrey de Grey and Dave Gobel's M Prize for anti-aging research has topped $1,000,000 in pledges. The first of many more millions, we all hope.

June 25 2005 - Passing the $1.3 million mark in pledges:

The number of endorsing organizations continues to grow and the news articles roll in. In short, things are moving forward; good progress is being made thanks to the many generous donors and volunteers who have stepped forward to date.

July 03 2005 - 50th member of The Three Hundred:

The first item of news, which happened to little fanfare so far, unfortunately, is that the Mprize recently celebrated its 50th member of The Three Hundred. In fact, as of now, there are 52 members of the 300, representing 1.3 million dollars in long-term commitments towards the prize.

July 17 2005 - A charity lunch with Ray Kurzweil is auctioned:

The dust has settled from the Methuselah Foundation charity auction for lunch with futurist and healthy life extension advocate Ray Kurzweil; congratulations to the lucky winner.

July 28 2005 - The $20,000 SENS Challenge is announced:

Regardless of which explanation is correct, biogerontologists apparently need an incentive to consider SENS. To that end, Technology Review is announcing a prize for any molecular biologist working in the field of aging who is willing to take up the challenge: submit an intellectually serious argument that SENS is so wrong that it is unworthy of learned debate, and you will be paid $20,000 if it convinces independent referees. In the case that even $20,000 is insufficient to motivate the relevant experts, we also invite contributions to the fund; anyone wishing to pledge should contact me.

September 27 2005 - The Muhlestein challenge grant met in a matter of days:

To the delight of all volunteers, donors and competitors involved in the Mprize competition, the Stan and Judy Muhlestein Trust $25,000 challenge has ALREADY BEEN MET. This stunning result is due especially to the generosity of David Gore, the newest member of The Three Hundred whose $25,000 donation swept the challenge. Thanks to all involved!

October 09 2005 - 66th member of The Three Hundred:

The sixty-sixth member of The Three Hundred signed up today, bringing the grand pledge total from these generous everyday philanthropists to $1.65 million - all in support of the realization of working anti-aging medicine, technologies capable of preventing and reversing the root causes of age-related degeneration.

October 17 2005 - Scott B. and Anne P. Appleby Charitable Trust donates:

It's always good to wake up to the news that my favored charitable cause has gained another respected donor organization. From Dave Gobel, news of another large lump sum for the Mprize for anti-aging research.

November 03 2005 - The $1,000,000 anonymous donation:

Let me be one of the first to thank the anonymous donor for his or her generosity and for greatly raising the level of vindication experienced by the Mprize volunteers and other donors. This is a big step forward for efforts to vitalize serious scientific progress towards a cure for aging. There is a long way to go yet - and more seven figure donations, I hope - but thank you, anonymous donor, for pushing the best present day effort into the major leagues.

November 04 2005 - Dr. Russ Heppel joins the advisory board:

Dr. Russ Hepple, one of the presenters at SENS2 who spoke about how caloric restriction helps preserve mitochondrial output in aged muscle has accepted the invitation to become an Advisor to the Mprize. Russ has been doing top work in the field of healthy life-extension and I am particularly pleased that his acceptance reinforces our mandate to be a global organization by the addition of a Canadian to our number.

November 15 2005 - Donations to LysoSENS Research accepted:

What is LysoSENS? This is the first Methuselah Foundation funded research program to deal directly with removing age-related damage - in the form of accumulated lysosomal junk - from within cells, based on Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS). Hence the name, LysoSENS.

December 02 2005 - LysoSENS funding passes $150,000

We are very pleased to announce that Three Hundred Member and long time Mprize supporter, Gary Hudson of HMX Inc., has donated fifty-thousand dollars to further the research of LysoSENS. LysoSENS is the novel approach of utilizing microbial enzymes to degrade otherwise indigestible junk that accumulates within cells with aging, eventually causing pathology. Thank you to Gary and all of our research supporters!

December 11 2005 - The Three Hundred Dinner, a Grand Success:

April Smith, calorie restriction enthusiast, Methuselah Foundation volunteer and healthy life extension advocate, reports on the foundation's December 8th Boston dinner for members of The Three Hundred - generous individuals who commit to giving $1000 each year to the MPrize in order to encourage and speed real anti-aging research - attended by Ray Kurzweil and Aubrey de Grey, and hosted by Jason Pontin of the Technology Review.

I left out the well-attended SENS 2 conference, a bevy of widely read mainstream media articles, and a number of other important events and efforts - but you get the idea. Success is good, and folks like you and I can help to make 2006 a banner year for healthy life extension ... so show the world that you support medical research for longer, healthier lives by making a donation to the MPrize.

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Another Potential Arthritis Therapy

A number of different genetic and gene therapy approaches presently hold out the promise of a cure for arthritis. Here, the Telegraph reports on a different way forward - tissue engineering of replacement cartilage: "Experts from the University of Bristol took just over a month to grow a half-inch piece of cartilage using stem cells, which are self-renewing and have the ability to grow into blood, bones or organs. ... Crucially, the new technique is expected to overcome problems of transplant rejection because the patient's own cells would be used to create the cartilage. ... Tests have shown that the laboratory-grown cartilage is of better quality than any previous attempts at tissue engineering. This means it should be 'springy' enough to work in a knee joint. Transplant trials on NHS osteoarthritis patients are expected within two years."


New Jersey Stem Cell Grants Issued

Via ScienceDaily: "New Jersey has become the first state to use public money to fund human stem cell research. The state announced $5 million in grants Friday to be split among 17 projects, the New York Times reported. Only three involve human embryonic stem cells, with others studying animals or using adult stem cells." This is small potatoes when compared against the much larger private investment in the field to date. The damage done by anti-research politics - such as attempts to ban vital technologies or whole swathes of medical science - is better measured by the extent to which it scares away risk-averse venture capital than by the posturing of public funding.


Top Science Stories of 2005

Kevin Perrott pointed out a LiveScience poll on the top science stories of 2005; the entry "Toward Immortality" might just be of interest to readers here.

"I think it's reasonable to suppose that one could oscillate between being biologically 20 and biologically 25 indefinitely." That's what eccentric researcher Aubrey de Gray, who thinks aging can be cured, told LiveScience in an interview this year. De Grey also runs the Methuselah Mouse prize for breakthroughs in extending the lives of mice, which researchers hope will spill over into progress to slow human aging. The purse of the M Prize, as it is called, grew beyond $1 million in 2005. As for hard science, one study showed that the buildup of mutated DNA triggers aging in mice. Another found stimulation of a certain gene in mice seems to delay bone weakening, artery clogging and loss of muscle fitness. Modern medicine is already allowing life expectancy to creep up, and it hit an all-time high in America this year. Ray Kurzweil, a computer scientist and writer, explained that his plan to live forever involves not tailgating, but taking 250 supplements and drinking lots of alkaline water and green tea.

About par for the course for a mainstream media commentary on healthy life extension research; quotes and factoids either wrong or out of context, casual slurs, and so forth. I would have expected better from a venture that is at least attempting to pass as a popular science site. Still, there it is in the top 10 list, a concrete sign that progress is being made in public awareness of serious anti-aging and longevity research. So get thee hence and vote it up a couple of notches - let's make the most of it while it's there.

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On Neurodegeneration

Randall Parker discusses the future of neurodegeneration and the importance of tackling this range of medical conditions to healthy life extension: "Barring advances in treatment the number of people in the world suffering dementia due to aging will more than triple by the year 2040. ... Obviously, lots of advances in medical treatments will occur in the interim. ... Brain rejuvenation combined with technologies to boost cognitive function will cause an enormous increase in average human productivity. The increases in human productivity will pay back the costs of medical research many times over. We are going to pay for the aging population one way or another. I prefer to pay for it by solving the underlying problem: reverse aging."


Early Nanomedicine

(Via What the mainstream describes as nanomedicine is probably best looked at as the application of nanoscale engineering to existing medical technology. It's a matter infrastructural improvement - smaller, faster, cheaper - and is largely taking place in diagnostics, biotechnology research, and drug delivery. "Nanomedicine is now within the realm of reality starting with nanodiagnostics and drug delivery facilitated by nanobiotechnology. ... There is definite indication of large growth of the market but it will be uneven and cannot be plotted as a steady growth curve. The largest expansion is expected between the years 2010 and 2015." Advanced nanomedicine - such as the use of mass-produced medical nanorobots to replace, enhance, repair or protect existing biological systems in the body - will be built upon a more advanced technology base that is yet to come.


More On Sirtuin Inhibitors

EurekAlert has more on surtuin inhibitors - I imagine that people have been dusting off their research for presentation over the past few weeks now that this area is suddenly hot stuff. "In lab tests, dihydrocoumarin (DHC), a compound found naturally in sweet clover and synthetically manufactured for use in foods and cosmetics, inhibited the activity of Sir2p and SIRT1, forms of sirtuin found in yeast and humans ... It's important to note that the role of sirtuins in aging is conserved in distantly related organisms such as yeast, drosophila and the small roundworm, C. elegans. So, it is not too much of a stretch to expect that sirtuins also control the aging process in mammals, including humans. In addition, sirtuins control many important cellular functions besides aging, and an agent that modulates sirtuins, such as DHC, could not only affect aging but also other critical functions, such as metabolism, neurodegeneration and cancer."


Sirtuins Everywhere

Sirtuins (such as Sir2 in yeast or Sirt1 in mammals) are in the news again; a set of releases and a new paper in the past few days on research into sirtuin inhibitors. I imagine that this research has been proceeding at a slow pace for a while and suddenly became hot when it was realized that, contrary to previous findings, inhibiting rather than enhancing sirtuins may a much better path to an extended healthy life span through metabolic manipulation. The biochemistry is more complex than one might have thought - which really should be no surprise to anyone who watches biomedical research - and the present state of knowledge is rapidly changing and evolving. With that in mind, I should point out a post on this topic from In the Pipeline that I missed last month:

The big question now, given all these divergent cell findings, is: will these guys live longer, or not? And what happens to them when you put them on a limited-calorie diet? Are they going to act like the replicative-aging models, or the chronological aging ones? (We'll leave the yeast-mouse contradiction out of it for a while). Perhaps the two mechanisms will fight each other to a standstill, leaving the animals with plain ol' normal lifespans, but with some tissues acting much younger than the whole-body age and some acting much older. Mice generally live around two years. I wonder just how many months ago these lifespan studies started. . .

You should read the whole thing; it's a better summary than my posts on the subject.

In any case, it's encouraging to see that research, in this field at least, has diversified to the point that promising work on potential sirtuin inhibitors was accomplished and ready to go in advance of the need. I'll momentarily put aside my skepticism regarding the potential of healthy life extension resulting from metabolic tinkering to note that I'm sure we'll see some very interesting mouse longevity experiments over the next few years - especially given that $3 million incentive to beat the present record.

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Next Up: Sirtuin Inhibitors

Following on the heels of recent surprising insights into the SIR2 protein and longevity in yeast, Elixir Pharmaceuticals is on the way towards developing inhibitors for the human version, SIRT1. "SirT1 represents an important new drug target, given its role in critical cellular processes such as lifespan modulation and the regulation of metabolism. Previously reported SirT1 inhibitors have low potency and low solubility making them poor candidates for drug development. Through Elixir's high-throughput screening campaign, we have discovered several highly selective low molecular weight SirT1 inhibitors that are 500-fold more potent than previously reported SirT1 blockers. These inhibitors are also cell-permeable and orally bioavailable, two characteristics that are invaluable for studying the biology of SirT1 and exploring possible therapeutic uses for SirT1 inhibitors." So it looks like mouse longevity experiments with reduced SIRT1 are in our future.


Stem Cells As Delivery Mechanism

Via EurekAlert, an approach to using stem cells to treat neurodegeneration. The cells are engineered "to produce a growth factor known as glial cell line-derived neurotrophic factor (GDNF). In some small but promising clinical trials, GDNF showed a marked ability to provide relief from the debilitating symptoms of Parkinson's. But the drug, which is expensive and hard to obtain, had to be pumped directly into the brains of Parkinson's patients for it to work, as it is unable to cross the blood-brain barrier. ... Svendsen's team implanted the GDNF secreting cells into the brains of rats and elderly primates. The cells migrated within critical areas of the brain and produced the growth factor in quantities sufficient for improving the survival and function of the defective cells at the root of Parkinson's."


Faking Scientific Results Never a Long-Term Prospect

News from the the laboratory of Woo Suk Hwang doesn't look so good - we'll see just how much or little of the research of the past few years remains as valid after the dust settles. This is unfortunate, to say the least; I'm not in a position to understand where this places the march towards regenerative medicine:

If the Korean lab can't clone embryonic stem cells from adults, can anybody? How close are we to achieving that goal in reality? How much of a real setback is it for stem cell science if we can't, given that the application of embryonic stem cells to therapies was probably some way off anyway?

Faking results just isn't a long-term prospect in scientific circles. This is why you can place a good deal more trust in the scientific method and scientific community than in other classes of human endeavor (such as, say, politics - the anti-science in many ways). The culture of science is based on truth and layer upon layer of verification, cross-checking and testing. The scientific community is ruthless when it comes to finding and punishing outright misrepresentation. Fabricate your results and you will be ostracised; many careers are already effectively over because of this affair, no matter what the final outcome.

And the obvious question: what were Hwang and company thinking? What made them think that they could fabricate results for a study that would inevitably receive almost unlimited scholarly attention? ... There's an old wry observation that if you look back at disastrously bad decisions made throughout history, you could probably find someone connected to each who would have said, "Well, it seemed like a good idea at the time." But I can't see how anyone in the Hwang lab could have ever even thought that.

Yes, indeed.

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Aubrey de Grey Keynote At Health IC

Biomedical gerontologist Aubrey de Grey speaks at more conferences in a year than I'll attend in a decade. One of the interesting upcoming events is the Health IC Summit in January: "The Health IC Summit explores disruptive innovations in healthcare, new developments that change the value proposition in the medical field, often quite dramatically. A three-day, four-track conference program of seminars, panels, and roundtables covers new science, technology and business approaches to stem cells and regenerative medicine, innovative patient care, medical informatics and a finance forum. ... Cambridge University's Aubrey de Grey extends the discussion by describing science's eventual cure for aging itself, leading to life spans of a thousand years or longer."


Progeria And Lamin A: Research To Date

From Medical News Today, a look back at two years of amazing progress in Progeria research: "researchers made a breakthrough in 2003, tracing [Progeria] to a spontaneous mutation in a gene encoding an important structural component of the cell nucleus, the organelle in which our DNA is stored, read out, and copied. ... The second set of results reveals mutant [lamin A] proteins turning up in the wrong place - too tightly linked to the membranes of the nuclear envelope - to be of much help during key stages of the cell cycle. The researchers believe that this localization failure of mutated [lamin A] proteins would severely compromise the ability of [Progeria] cells to engage in normal DNA replication, a probable factor in their rapid march to premature senescence. Whether similar missteps and miscues by nuclear lamins are part of 'normal' human aging is the question that draws researchers onward."


Control Is The Key To Cell Therapies

From EurekAlert, a good demonstration of the sort of control over cellular processes that is at the heart of progress in cell therapies: "The key gene that the scientists studied is called brahma-related gene-1 (Brg-1) that is found in both mice and humans. ... This research shows us that in mice, Brg-1 is a critical signal that prevents stem cells from turning into neurons at the wrong time. However, since we can manipulate Brg1 expression in stem cells in culture, we now have a powerful way to generate neurons that could be used to replace cells lost in a variety of diseases and conditions that affect the brain and spinal cord. That is our next step. Since the process only involves a single gene, it is highly amenable for the development of drugs targeted at promoting stem cell differentiation in the adult nervous system."


Aubrey de Grey on 60 Minutes, January 1st

I have it on good authority that the 60 Minutes feature that includes biomedical gerontologist Aubrey de Grey and his work will be aired on January 1st ... but we all know how these schedules tend to shift hither and thither. So keep your eyes open and expectations low - television remains the strongest bastion of gleeful ignorance and lowest common denominators in mainstream media, after all.

Soundbites and reflexive "balance" do not lead to a useful medium for discussions of the merits and cut and thrust of science, sadly - advocacy would certainly be an easier job if matters were otherwise.

UPDATE 01/01/2006: It went very well indeed, as it turned out - one of the most positive mainstream media pieces on the Strategies for Engineered Negligible Senescence (SENS) yet. I am pleased to have been proven wrong in this instance. See the latest post on the topic for a link to the transcript.

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The Ongoing Search For Longevity Genes

Betterhumans notes another modest step forward in attempts to match genes with longevity or resistance to age-related disease (although I would object to any use of the term "successful aging" - no such thing! Yet). "While previous research found that genes make important contributions to exceptional longevity, the goal of this study was to identify regions of the human genome that contributed, along with lifestyle factors, to reaching age 90 with preserved cognition. ... Specifically, Dr. Zubenko and his research team attempted to identify specific genetic sequences present in older individuals that may be linked to reaching older ages with preserved cognitive abilities, or conversely, specific genetic sequences present in younger individuals (and not present in those over age 90) that may impede successful aging."


Insight Into Werner Syndrome

Investigations into accelerated aging conditions have helped to shed light on the biochemistry of "normal" aging. Via Newswise: "A University of Maryland researcher and his team have discovered a key to the cause of the accelerated aging disease Werner syndrome ... caused by a genetic mutation of a specific gene - the WRN gene, which some scientists think hold the key to understanding something about the aging process. Scientists also know that humans have five types of RecQ helicase proteins, including the WRN protein, which is expressed by the WRN gene. These proteins function as safeguards to maintain genome integrity. Mutations in three RecQ helicase proteins have been linked to genetic diseases. But they don't know what goes wrong in this group of proteins that causes the aging process to go haywire. Hu and his team singled out the WRN protein, or enzyme, to look for some answers."


Folding@Home Progress For the Longevity Meme Team

The Longevity Meme Folding@Home team has made great progress since hitting rank 500 a few short months ago. As an examination of the statistics shows, the team has now reached rank 400 - congratulations all round!

Folding@Home is a way to donate spare processing cycles to advance our understanding of human biochemistry; this understanding forms the smallest blocks on which modern biotechnology and medical research is built.

Proteins are biology's workhorses -- its "nanomachines." Before proteins can carry out these important functions, they assemble themselves, or "fold." The process of protein folding, while critical and fundamental to virtually all of biology, in many ways remains a mystery.

Moreover, when proteins do not fold correctly (i.e. "misfold"), there can be serious consequences, including many well known diseases, such as Alzheimer's, Mad Cow (BSE), CJD, ALS, Huntington's, Parkinson's disease, and many Cancers and cancer-related syndromes.

So join in - download the client, join our team and help to make a difference to the future of medicine.

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What Do Life Extension and Anti-Aging Research Look Like From a Distance?

Occasionally, it's good to suffer a reminder that we advocates for research into healthy life extension medicine - and the development of working, scientific anti-aging therapies capable of repairing age-related cellular damage - have a great deal of work left to do. This particular reminder comes in the form of a Maclean's article: the healthy life extension movement as seen from the outside, from a distance, with a typical level of man-in-the-street understanding. From this perspective, lie-down-and-die aging apologist Dr. Weil stands on the same platform as the worst of the anti-aging marketplace, right next to Cynthia Kenyon's prodigously long-lived worms and Aubrey de Grey's Strategies for Engineered Negligible Senescence - no differentiation between nonsense, marketing and science, nor between factions of scientists with quite different aims and opinions.

Realistically, this is about we can expect for anyone with no real interest in what's going on - we have to do a far better, more expansive job of framing the picture for the public if we want widespread support for the right sort of anti-aging research. That said, progress on the media and public awareness front in recent years has been rather gratifying. The Macleans piece ends on this note, after all:

After talk of all these experiments, Weil's final advice is rather disappointing. "Get adequate rest and sleep." "Exercise your mind as well as your body." "Learn and practise methods of stress protection." What, when there's a worm just lying there increasing its lifespan by leaps and bounds? Readers might want to wait for the pill.

While a flawed statement in a number of ways, it illustrates that biomedical gerontologist Aubrey de Grey is quite right in his notion that extremely long-lived, healthy mice - when they arive - are going to provide a real boost in public understanding and support for scientific anti-aging research.

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Overhyped, But Interesting

(Via the Muskogee Phoenix). A research team are claiming their discovery of pluripotent stem cells in bone marrow to be an important discovery: "University of Louisville researchers have coaxed stem cells from adult mice to change into brain, nerve, heart muscle and pancreatic cells." I think this is greatly overhyped; small pluripotent - or even pseudo-embryonic - cell populations have been discovered elsewhere in the body over the last year or two. This is not to demean the promise offered by a local source of suitable adult stem cells for tissue engineering and regenerative medicine - it's a big deal. But that isn't cause to issue calls to halt the vital work of embryonic stem cell research.


Regrowing Pancreatic Islets

From Scientific American, a look at progress towards diabetes therapies in the form of regenerative medicine for the pancreas: "In newly diabetic mice, the results were spectacular. After two weeks of treatment, the beta-cell mass had tripled, the insulin content had increased eightfold, and the blood glucose concentration had fallen to normal levels. It did not go so well in mice with long-standing diabetes: their glucose levels fell substantially, yet they needed some immunosuppressive medication. ... Even a partial regeneration in patients would at least get around the shortage of donor tissue and would probably require less immunotherapy; native cells would need defense from autoimmunity alone, not from that and organ rejection combined."


Stem Cell Trial For Crohn's Disease

Two years ago, I pointed to a therapy for Crohn's disease as a good example of progress in stem cell research. Two years on, companies like Osiris Therapeutics are still navigating the oppressive FDA regulatory maze in order to bring a demonstrated treatment to market. "Osiris Therapeutics, Inc. announced today that it has received clearance from the U.S. Food and Drug Administration (FDA) to begin enrollment in a Phase II clinical trial to evaluate the safety and effectiveness of [an] intravenous formulation of mesenchymal stem cells [obtained] from the bone marrow of volunteer donors between 18-32 years of age." There is a good reason why responsible, commercial stem cell therapies are presently only taking place outside the US, and that something is a three-letter abbreviation for the worst aspects of government interference in medicine and freedom of research.


Obesity, Loss of Vision

As yet another gentle reminder of the weight of scientific evidence demonstrating that excess fat is a very bad thing for long term health, we have this report from Israel21C: "being overweight - in addition to the known numerous health risks such as heart disease and cancer - also greatly increases your chances of losing your vision. Following a review of than 20 research studies on thousands of patients around the world, [scientists] found a consistently strong correlation between obesity and the occurrence and development of all four of the major eye diseases that cause blindness ... In some of the cases the reasons for linkage between obesity and these diseases was clear - for example, since glaucoma, diabetes and [age-related macular degeneration] all affect the vascular system and excess weight is known to create pulmonary problems, the blood vessels in the eye are affected, and sight deteriorates. But when it comes to cataracts, the link is less obvious."


Reports From the MPrize Three Hundred Dinner

April Smith, calorie restriction enthusiast, Methuselah Foundation volunteer and healthy life extension advocate, reports on the foundation's December 8th Boston dinner for members of The Three Hundred - generous individuals who commit to giving $1000 each year to the MPrize in order to encourage and speed real anti-aging research - attended by Ray Kurzweil and Aubrey de Grey, and hosted by Jason Pontin of the Technology Review. Read on for the details:

More than thirty people attended: Three Hundred members, their partners or friends, and Jason Pontin, editor of Technology Review, who hosted us, as well as his angelic staff person Leila who went above and beyond the call of duty to make the event work... including chilling a Methuselah of champagne in her own car all day!


One of the most interesting conversations I had was with Jason Pontin, the editor of Technology Review, who hosted the event in his large conference room. Many were dismayed by his rather scathing editorial on the subject of, among other things, Aubrey de Grey.


I found Jason's conversation enlightening and entertaining... it just goes to show how rational, thoughtful people can have honest disagreements and still enjoy a glass of pinot noir together. I extracted a promise that he would allow me and MR to make him dinner at our house the next time he's in Philadelphia, and I plan to hold him to it.

It was wonderful to see Aubrey again, as always, and we made some good progress planning upcoming SENS/Mprize events... stay tuned!

Separately, the winners of the MPrize charity auction for luncheon with Ray Kurzweil also held their event recently - and April was there to cook the calorie restriction way:

Ray talked with us about technology, nutrition, inventing, and all sorts of things. I missed quite a bit of the conversation running back and forth to the kitchen, but I definitely enjoyed being in the company of such brilliant people. Ray's dining room was a beautiful setting, with a view of the lake and amazing art worked in with a history of family pictures.


Finally it was time to go, and the winners and I spent the car ride back to MIT discussing our fascinating meal with Ray Kurzweil. We all felt like we had had a priceless experience. Being in the company of someone who has blazed so many trails could seem intimidating, but Ray was so friendly and gracious that we all felt at ease almost immediately.

And he liked the food. That's what really matters.

Donate to the MPrize for anti-aging research and you'll find yourself in good company.

UPDATE: Here's another report from an attendee.

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From a Sample of One

Centenarian interviews and general interest articles are a firm favorite in the mainstream media - largely, I suspect, because they require little work on the part of the journalist and are almost always well received by the audience. An unconscious assumption is at work in the reader; that a centenarian has something constructive and helpful to share about how they achieved such longevity ... but this is certainly not the case in reality. If pressed, could you provide a rationale for some random facet of your health history? Of course you could, but how likely are you to be right?

You can't do anything with a sample of one, and it's very hard to pin down even the obvious whys and wherefores of your own health, never mind relative progress or decline over decades. Think about the time taken to understand how specific foods alter your moods, for example - and that's an easy task in comparison to most. It has taken years armed with modern biotechnology to even scratch the surface of human longevity, and this working from huge groups of the old and healthy.

The timeless, easy popularity of centenarian articles illustrates something fundamental, I think - that most people really are interested in living much longer, healthier lives. It's just a question of how you present the options.

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SAGE Crossroads, Woo Suk Hwang

SAGE Crossroads has put up a video and podcast interview with stem cell researchers Woo Suk Hwang and Jerry Schatten, filmed prior to their public split. There is no transcript yet, unfortunately, and probably won't be for a few weeks given past timing - so dive in while it's fresh. If you have an interest in the advance of stem cell based regenerative medicine, you should certainly take the time to watch or listen to the interview. This field of research offers a plausible path to effective therapies for a wide range of age-related conditions and degeneration. The earliest results will likely involve the replacement of failing, vital tissue - small regions in the heart, liver, or parts of the brain, for example - but cell therapies ultimately offer much more than that.


State Of Play At CIRM

The Ledger looks at the state of Proposition 71 and the California Insitute for Regenerative Medicine: "After nearly an entire morning of sometimes heated debate the other day, the board overseeing California's $3 billion stem cell research institute took action. It asked the organization's president to draw up a plan for how to draw up a strategic plan. That is the way it has been going lately for the state's closely watched foray into the frontiers of medical science. More than a year after 59 percent of Californians approved an ambitious program to harness human embryonic stem cells to treat diseases, not a single dollar has yet been spent on research. Instead, the effort has been hobbled by litigation that has kept the project from raising money. It has been second-guessed by public interest groups and legislators. And it has been consumed by the bureaucratic minutiae required to set up rules for administering grants."


Myostatin Therapies On The Way

The New Scientist reports that "two treatments that block a protein called myostatin, which slows muscle growth, are now in the pipeline." You may recall the initial work on muscular mice that pointed the way to the biochemical mechanisms controlling muscle growth. Myostatin therapies have the potential to address age-related muscle loss as well as wasting diseases. "The first approach, announced this week, aims to use a drug to mop up myostatin. Meanwhile a second method, which is already in clinical trials in people with muscular dystrophy, uses antibodies to disable the protein. ... The company hopes to have initial results by late 2006."


When Healthy Life Extension Is Not Healthy Life Extension

You have to read studies on the life-extending benefits of compound A or product B on rodents very carefully these days, especicially now that marketing departments feel they can get milage from press releases that mention life extension in mammals. Here's a good example:

In the study, rats prone to many of the manifestations of aging were fed diets containing ChromeMate, which increased their average life span by 22 percent compared to rats fed the same diet without ChromeMate. Rats fed ChromeMate also experienced lower systolic blood pressure, lower circulating glucose levels, and a trend toward lower, normalized hemoglobin levels, a long-term indicator of blood sugar status. There were no abnormalities in blood chemistry, kidney or liver function in any group.

The key questions here - not addressed in this press release of course - would be a) how these rats fared against unmodified, untreated control rats who were not "prone to many of the manifestations of aging," and b) did they control for the effects of calorie restriction? Put anything in the diet of mice that makes them less inclined to eat - because of nausea or otherwise - and it'll extend their life span via the as-yet incompletely understood biochemical processes of calorie restriction.

It's certainly good and progress to demonstrate that you can mitigate the harmful effects of metabolic conditions that reduce healthy life span, but there is a big difference between preventing reductions in life span that accompany disease and increasing the best possible life span.

Of course, when you're selling a product, you're selling a product - subtle but very important distinctions need not apply. The long-time readers here have no doubt seen similar claims come and go, and have an appropriate level of skepticism when it comes to these matters.

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Stem Cell Lines, Practicality

A BBC article gives us an idea of the practicality of regenerative medicine, research and tissue engineering based on embryonic stem cells: can it be done with few enough stem cell lines to make it a near-term prospect? "The scientists calculated that cells from 150 random embryos would, on average, be enough to provide the best possible match for 13% of recipients, a favourable level of match for 65%, and some use for as many as 85%. ... When the donor pool was narrowed down to those with the best possible set of genetics, the researchers found that just 10 stem cell types would be enough to provide a favourable level of match for 78% of recipients. ... What this research tells us is that the number of lines needed to achieve a significant clinical value is in the practical realm."


Recycled Nonsense

What motivates people to write columns mocking those working towards reducing pain, suffering and death by developing medical technologies to extend healthy life span? I can't visualise these humorists writing a column to deride the cancer research and advocacy community, or to cry out that everyone should just get Alzheimers, suffer, die and be done with any attempt to avoid that fate. Yet there is no fundamental difference between seeking a cure for any specific age-related condition and seeking a cure for all age-related degeneration. It's all about preventing suffering and death ... I think you have to lock yourself into a particularly blank mental room to avoid that truth.

Worse, this column in the normally - at least moderately - sensible Wired simply regurgitates the old, tired disproven, debunked, plain old wrong arguments against healthy life extension. Malthusianism on resources, the prospects for boredom, economic misapprehensions and false extrapolations, accusations of hubris. The hubris thing always annoyed me - since when is it hubris to visit a doctor, to seek a cure for a medical condition, or to support medical research and better health?

I can't help but feel that many of the people opposed to healthy life extension simply don't like living all that much - why else would they want to die? Life is what you make of it; if you're not making anything of it, there's always the option to leave. But please let the rest of us attempt to improve things - medicine, science, longevity, the works - unmolested.

Or at least work on developing some new, un-debunked, non-disproven talking points with which to take your cheap shots at people attempting to better the human condition.

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Stem Cells: To Store Or Not To Store?

(From the Guardian). A number of ventures are making it possible to store your stem cells for possible future needs, although the storage of newborn cord blood is more common. The price will drop if this service takes off as a business proposition. The advantage is that your stem cells presently have less age-related damage - genetic or otherwise - than they will at any point in the future. This is a speculative hedge against the path of medical technology in the years ahead: will it be the case that stem cells are vital to a regenerative therapy you require, but that no effective method exists to compensate for age-related cellular damage in your cells at that time? In that scenario, you'd probably be glad you banked your cells in a past decade.


Mechanisms of Metastasis

If you want to stop cancer from spreading throughout the body, a good start is to understand exactly how this process takes place. Via the BBC: "primary tumours emit chemical signals. These make the target sites for secondary tumours sticky and direct bone marrow cells to them to secure a foothold for arriving tumour cells. ... Once there, they cluster in groups, forming a support structure which stabilises the malignant cells that arrive later to begin forming a secondary, or metastatic, tumour. ... New York's Cornell University used antibodies to block bone marrow cells' migration in mice, and believe their work could help humans." Cancer is one of the largest obstacles to be overcome on the way to greatly extended healthy life spans - but the rate of progress is promising.


Preventing Neurons From Dying

A good deal of hype in this LEF News reprint, but it sounds like they have something worthy of further research and development: "The studies show how a naturally occurring protein called KDI tri-peptide (KDI) can serve as a defense mechanism to prevent brain damage normally caused by Parkinson disease. They also demonstrate KDI's potential to treat ALS as well as stroke ... The second study looked at humans and mice with ALS, a devastating neurological disease that causes neurons in the brain and spinal cord to die ... It appears that the body tries to protect itself by producing KDI, but in most cases it is not able to produce enough KDI on its own to stop the damage. ... the brain reacts to stroke damage by naturally producing KDI in the healthy tissue surrounding the seriously damaged brain areas. ... We are currently testing KDI's ability to prevent stroke damage, and based on our results so far I feel very optimistic."


More TheraVitae Coverage

Israel21c has more on TheraVitae and their stem cell heart therapy: "We've treated 65 patients, and the number is going up daily, and we're very optimistic. Based on the data gathered, it will be much easier to get initial approval for Phase I trials in the US, which we're planning to apply for within the next few months ... As the therapy is still in its early stages, only those classified by doctors as 'no option' - meaning that conventional solutions such as angioplasty and bypass surgery have been exhausted - are eligible. ... We're treating patients that have no other therapeutic option. There's no pill they can take, their lives are headed in one direction. This therapy is one that can bring them in the opposite direction." This flurry of press coverage is the visible sign of what will soon be a wave of commercialized stem cell therapies.


Support the CR Society

The CR Society is holding a membership drive to help support their advocacy of calorie restriction (CR) and encouragement of CR research for longer, healthier lives. I think that this qualifies as a worthy goal:

Hi everyone,

I'm Brian Delaney, President and one of the co-founders of the CR Society.

Most of you know the CR Society as a useful and informative email list and Web site, where you can find the most up-to-date information about calorie restriction and the support of a community of people who want to live long and healthy lives. What you might not know is that the CR Society is also a non-profit organization that sponsors research about CR, gets the word out to the public about the potential benefits of CR, and serves its members by providing resources to help them improve their lifestyle and health. In addition to the email list and Web site, the CR Society also sponsors the CR Society Human Cohort Study, a study aimed at discovering the effects of CR on real people. The CR Society is also working on a list of CR and life-extension friendly physicians, so that CR practitioners world-wide can find health care providers who are in tune with their needs and health goals. As it grows, the CR Society aims to encourage and provide resources for further research into the best methods of practicing CR: much remains to be discovered about optimal nutrition, exercise, meal timing, and macronutrient ratios that promote maximum health. (Descriptions of some of our newer projects will follow over the coming weeks.)

All of this takes money, so on behalf of the CR Society Board of Directors, I'm kicking off the first CRS membership drive with a personal appeal to you to join the CR Society. For $35 per year (if you join before the end of the year) you will receive invitations to CR Society regional gatherings, a subscription to the CR Society newsletter, "The CRS Insider," plus discounted registration fees to all CR Society conferences -- the next one will take place in Tucson in April. And you'll know that you've done your part to support the organization that provides you with the information and support you need to follow the only lifestyle shown to slow biological aging in mammals. During this special week, we're also offering a signed copy of The Longevity Diet, an introduction to CR that I co-authored with Lisa Walford (daughter of CR pioneer, Roy Walford, and one of the co-founders of the CR Society) for every Lifetime Membership -- that's a one-time donation of $500 or more.

Please take a moment to support the CR Society. Please follow the link below to join now!

Brian Delaney
CR Society President and Co-founder


The CR Society conferences alone are worth the price of admission. The 2006 conference looks like it will be just as well attended as the last in the series, including the usual contingent of noted researchers.

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Time On TheraVitae

Time takes a look at TheraVitae and its newly commercialized stem cell therapy: "Fulga's treatment repairs damaged or inactive heart tissue using adult stem cells harvested from the patient's blood and processed outside the body by mimicking the body's environment. Unlike other stem-cell therapies, which make use of bone marrow or - more controversially in the U.S. - the blood of human embryos, Fulga believes the procedure patented by TheraVitae is simpler, safer and less invasive. ... Fulga and his colleagues are tapping into the estimated $54 billion-a-year market of cardiac patients in need of treatment. The company projects that it will break even soon. 'We want to be the Intel of cell therapy.'"


A Good Introduction to the Strategies for Engineered Negligible Senescence (SENS)

Michael Anissimov, whose interests these days lie more in the realm of general artificial intelligence, has penned a good introduction to SENS, the Strategies for Engineered Negligible Senescence. You should certainly read the whole thing:

It is an engineering approach that seeks to slow and then halt aging processes that are the side effects of our body's metabolic cycles. The proposal originates with Dr. Aubrey de Grey, a Cambridge biogerontologist who has appeared in CNN, the New York Times, New Scientist, Popular Science, MIT's Technology Review, Fortune magazine, BBC News, etc. De Grey's Methuselah Institute has raised $3M in donation committments towards the Methuselah Mouse Prize, which rewards researchers who achieve breakthroughs in substantially extending the lifespan of middle-aged laboratory mice. After reliable life extension is achieved with mice, therapies for humans would follow.


Quite a project, but this framework gives us an abundance of starting points. And people are beginning to take it more seriously. SENS is an effort I encourage people to give to that surpasses the humanitarian value of the vast majority of conventional charities.

Donations to the MPrize for anti-aging research go towards encouraging and supporting the science that will extend our healthy life spans - and are always greatly appreciated. Step up and make a difference to the future of medicine! If you maintain your own blog, take the time to pen your own thoughts on SENS. Every addition to the worldwide conversation on the ways and means of radical life extension helps to build support - and support ultimately translates into funding for research, one way or another.

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Interview With Michael Rose

The New York Times interviews evolutionary biologist Michael Rose: "the common assumption is that young bodies work and then they fall apart during aging. Young bodies only work because natural selection makes them healthy enough to survive and breed. As adults get older, natural selection stops caring about them, so we lose its benefits and our health. If you don't understand this, aging research is an unending riddle that goes around in circles. ... aging isn't some general breakdown process, like the way cars rust. Aging is an optional feature of life. And it can be slowed or postponed. This implies that controlling human aging does not require the violation of some absolute scientific law. Postponing human aging is not like building a perpetual motion machine or faster-than-light space travel. It is a scientifically reasonable thing to try."


Phoenix Biomolecular, an Odd Bird

A glance through the Phoenix Biomolecular website shows it to be an odd bird, appearing as something of a hybrid between interesting science and "anti-aging products" of the sort that immediately trigger my nonsense detector.

The interesting science relates to methods of manipulating cells by delivering biochemical compounds to interact with cellular machinery. If you can safely deliver enzymes, DNA, and so forth, into cells throughout the body, a range of possible technologies open up for consideration. From the sound of things, Phoenix staff are focusing on the manipulation of telomeres as a starting point.

Telomeres are the protective caps at the end of chromosomes that shorten with cell division; average telomere lengths become shorter with advancing age. Telomere length, related cell division mechanisms and the activity of telomerase (the enzyme that lengthens telomeres) are associated with aging, cancer and the properties of embryonic stem cells, amongst other important areas. The interplay between lengthening, shortening and cell division is supposedly a finely balanced evolutionary compromise between death by aging and death by cancer. The telomere theory of aging, which supposes all aging to stem from telomere erosion, is largely discredited, however.

That said, the manipulation of telomeres has shown promise for a range of therapies for age-related conditions. Telomere therapies are hoped to rejuvenate the aging immune system, or halt cancer, to pick two examples.

So on to the nonsense-triggers: the Phoenix website gives prominent space to the concept of skin rejuvenation via anti-aging creme. I'll be the first to admit that skin rejuvenation is a worthy goal for a number of actual therapeutic reasons that have nothing to do with appearance, but that just isn't coming across in the Phoenix presentation. Their online materials presently look and read much like those put out by the dubious end of the "anti-aging" marketplace. Whatever the merits of Phoenix's scientific approach and their team, their public face just isn't giving me the warm and fuzzies I'd expect from a company performing serious work on age-related conditions.

So we shall see. Best of luck to the Phoenix team if they are indeed a serious venture with good backing.

While we're on the subject of telomeres, you might be interested to read Aubrey de Grey's WILT proposals. He thinks we should indeed be lengthening telomeres be removing telomerase throughout the body as a way to counteract cancer - an ambitious undertaking, and one of the more speculative components of the Strategies for Engineered Negligible Senescence (SENS). To my mind, any sufficiently effective range of cancer therapies and preventions would do the job. The size of the boat and the amount of paddling don't necessarily matter so long as you make it across the river.

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Beyond the Horizon

Newsweek mentions healthy life extension and the future of nanomedicine in this question and answer session: "In the 20th century, in the developed nations, our life span increased from about 50 years to about 80 years. In just 100 years, our species (which has been on earth for more than a million years) increased its life span by 60 percent. Right now changes in our lifestyle have more power to extend our life span than any medicines yet invented: sitting around waiting for a magical life-extending elixir isn't healthy." But this truth will change - if we all help to ensure that science develops healthy life extension medicine. If you are mindful enough to save for retirement, why not also help to ensure that future medicine can extend your healthy life span. The distance to the horizon depends on where you stand, after all.


The Late Life Plateau

ScienceDaily notes the interesting phenomenon whereby the decline of aging - measured by your statistical chance of dying in each year - appears to plateau in late life. That plateau is at a high chance of dying each year, of course, but it raises questions regarding how and why age-related degeneration happens. Is it programmed events, decay of components in a complex system, or a mix of both? Researcher Michael Rose adopted the phrase "biological immortality" to describe this behavior in flies - although he means something quite different from what most of us think when hearing those words. If you're interesting in reading more on the topic, his is the first essay in The Scientific Conquest of Death, now available online for free.


Reverse Engineering the Healing Process

If medical science is going to improve upon the natural healing process or restore failing healing capabilities for the aged, then it certainly can't hurt to know - in great detail - how healing actually works. There's still work to do and much to decipher down at the biochemical, genetic and cellular level, as a recent release makes clear:

Clinicians have known for some time that when the skin is abraded new cells come from the hair follicle. What remained a mystery was the exact nature of the origins of the new cells-specifically, what percentage stems from the deep follicle and what percentage from the epidermis near the wound.

Cotsarelis' team found that adult stem cells from the lowest portion of the hair follicle, or "bulge," quickly ascend the follicle in response to wounding and ultimately comprise about 30 percent of the new cells in a wound when it first starts to heal. In addition, the stem cells respond rapidly to surface wounding-within two days-by generating short-lived "transient-amplifying" cells that respond to acute wound-healing needs.

Using a genetically engineered mouse designed in their lab, the researchers were able to visually follow the fate of the stem cells as they migrated from deep within the skin to the surface wound site. The mouse stem cells express a reporter gene that encodes an enzyme, which can be detected with a special blue-color reaction. "We could see blue lines coming from the follicles going toward the center of the wound," says Cotsarelis. "They formed a striking radial pattern like the spokes of a wheel."

It's encouraging to see just how sophisticated modern biotechnology has already become - an experiment of this sort would have been an expensive pipe dream even 10 years ago, based on knowledge not yet obtained, and tools not yet built or standardized.

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A Middle Path Of Optimism

Via Gadget, here is a piece on the future of aging by British Telecom futurist-in-residence Ian Pearson: "Nor will getting older imply having to slow down and put your feet up until much later in life. We can expect to live longer, but also remain healthier, almost up to the last minute. We'll still die, but not so gradually. ... And for those of us that are still young today, technologies such as nanotechnology will come on stream just in time for us to benefit from micro-machines living inside our bodies, reinforcing the body's own defences and maintenance systems. Longevity will increase, health will increase, vigour will increase, and old power will increase. I wouldn't go so far as to say I can't wait, but I'm certainly not worried about getting old." Pearson is not sold on actuarial escape velocity, it seems, but the end of health and life is something that can potentially be put off for a very, very long time.


Prostate Cancer Stem Cells Identified

The Times reports that researchers have identified cancer stem cells for prostate cancer: "Identifying the cancer stem cell is the most important element: stem cells feed the whole repertoire of cancer cells that complete the tumour. ... the equivalent of finding the 'engine room' that drives cancer to grow, spread and resist treatment such as chemotherapy and radiotherapy. Finding such stem cells is like looking for a very small needle in a rapidly growing haystack. This study has identified the first 'hints' that such novel stem cells do exist in prostate cancer." If you can eliminate the errant stem cells at the root of a cancer, you eliminate the cancer - the convergence of stem cell research, immune therapy and other very precise cancer treatments means that scientist should soon be able to do just this.


Science to Watch in 2006

Based on the past couple of years, I think that the following science is worth watching in 2006:

1) Mitochondrial research

The tools for manipulating mitochondria - our cellular power stations - and associated technology demonstrations have become much more impressive of late. Given that mitochondrial dysfunction is strongly linked to a number of diseases as well as age-related degeneration, advances in this area offer a great deal of potential.

2) Commercialization of stem cell therapies

The gate is already open, and the first stem cell medicine companies are already offering limited services. I'm expecting to see a range of first generation stem cell therapies, mostly using adult stem cells obtained from the patient, become the subject of commercial efforts outside the US during 2006.

3) Calorie restriction biochemistry

2005 was a year of progress, learning and unexpected twists for research into the mechanisms of calorie restriction and other links between metabolism and longevity. Look for more of the same to come.

Given that a number of venture-funded groups will enter their second year of investigating calorie restriction biochemistry and genetics in 2006, we should soon be hearing about initial attempts to apply this new knowledge to the treatment of diseases. That said, I imagine it will look very much like old school drug development; trying to find compounds that will flip the right cellular triggers (for some subset of the population, with a few side-effects as possible). Our ability to look and understand outpaces our ability to manipulate - and greatly outpaces the stifling regulatory regimes tied to the status quo and last century's medical development process.

4) Gene therapies and immunotherapies

Both gene therapies and immune therapies seem to be moving quickly from "promising, but no results" towards "working therapy in hand." I would be very surprised if 2006 passes by without important developments and further attempts to cure age-related conditions using these methods.

5) Activism for real anti-aging research

If real, meaningful anti-aging research isn't funded, then the end result - longer, healthier lives - won't come to pass in time to help us. If the regulatory process makes it impossible to approve or market therapies to address the aging process, then research won't be funded. We have a long way to go in terms of steering the research community and funding organizations towards a full-press assault on the problem of degenerative aging. While many helpful or related fields of medicine show progress, we have to move beyond incidental life extension if we want to see a cure for aging within our lifetime.

Fortunately, the efforts of organizations like the Methuselah Foundation are making an impact - we must keep up the good work and continue our support for greater funding, freedom of research, and change in the way scientific community regards longevity research.

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Investigating Memory Loss

(Via Why does the aging brain lose memory abilities? "The traditional thinking is that when older people lose the ability to 'bank' new memories, it may be because of deterioration in the brain's temporal lobe. Loring believes it is possible that some older people actually lack the attention span to log new information into their memory, which places the problem in the prefrontal cortex - the brain's attention center - rather than the temporal lobe. ... We have all the tools in our hands; the problem is combining the right people with the right cells to answer the question of what kind of genes contribute to long-term memory formation. Nobody really understands on the level of specific cells how many genes work together. We are excited because this is the first time we will be able to monitor all the genes in specific neurons."


Towards Prosthetic Limbs

What will arrive first: tissue engineered or regenerated replacement limbs, or prosthetic limbs that function just as fully as the original? From Wired: "Cyberhand would be attached to amputees below the elbow and covered by several layers of synthetic material that would seek to copy the features of a natural hand by making the prosthetic replacement soft, compliant, and flexible. ... Patton says it represents 'the first prosthetic hand that really is fully integrated into the nervous system.' Linked to the nerves by tiny electrodes and biomimetic sensors, it would let patients sense the position and movement of the hand as well as stimuli from the outside environment." There is still a great deal of work to do, but scientists are making impressive progress in tapping into the peripheral nervous system.


Another $50,000 for LysoSENS Research

Good news from the Methuselah Foundation:

We are very pleased to announce that Three Hundred Member and long time Mprize supporter, Gary Hudson of HMX Inc., has donated fifty-thousand dollars to further the research of LysoSENS. LysoSENS is the novel approach of utilizing microbial enzymes to degrade otherwise indigestible junk that accumulates within cells with aging, eventually causing pathology. Thank you to Gary and all of our research supporters!

This is on top of more than $100,000 that Hudson has already donated to the Methuselah Foundation, to assist and encourage medical science in the development of viable strategies to prevent and repair age-related cellular damage - and thus defeat aging.

The MPrize itself has passed $3 million in cash and pledges this year, thanks in large part to the recent anonymous $1 million donation, but also due to the dedication and generosity of many hundreds of other people. "All" that stands between us and the first commercially available, working anti-aging medicine is hard work and funding. This is a huge scientific project, but then so is the battle against cancer, and that's moving forward - the sooner we get started, the sooner we'll achieve results.

So do more than simply wish for a far longer, healthier life - help make the necessary medical technology a reality by donating to the Methuselah Foundation.

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Preventing Age-Related Muscle Loss

Promising research is noted at EurekAlert: "Muscle in adults is constantly being built and broken down. As young adults we keep the two processes in balance, but when we age breakdown starts to win. However, adding the amino acid leucine to the diet of old individuals can set things straight again. ... After the age of 40, humans start loosing muscle at around 0.5-2% per year. ... The team of researchers believe that the age-related problem results from defective inhibition of ubiquitin-proteasome dependent proteoloysis, a complex degradative machinery that breaks down contractile muscle protein, and that leucine supplementation can fully restore correct function." It's good that a diet change could potentially patch this issue, but it is likely that a real fix - and greater understanding of biochemistry - will come from the follow-on research that this discovery inspires.


Good Mitochondrial Research

Something a little more scientific today from the Journal of Physiology, but a good sign: "The mitochondrial theory of ageing proposes that the accumulation of oxidative damage to mitochondria leads to mitochondrial dysfunction and tissue degeneration with age. However, no consensus has emerged regarding the effects of ageing on mitochondrial function, particularly for mitochondrial coupling (P/O). One of the main barriers to a better understanding of the effects of ageing on coupling has been the lack of in vivo approaches to measure P/O." The researchers go on to show a way of accomplishing this task - which means groups working on ways to repair age-damage mitochondria will have an objective measure of how successful they are.


UK: More Public Stem Cell Funding

Via the Financial Times, news that government funding for stem cell research will double in the UK: "between £650m and £820m is to be invested in stem cell research over the next 10 years." Increased funding is the case in most stem cell research communities around the world; it's a pity that a sizeable fraction will be in the form of poorly managed public money, but we can expect to see an acceleration of results in the years ahead - highly publicized public funding is always outweighed by less reported private investment. From a long term perspective, perhaps the most important product of stem cell medicine will be a greatly increased understanding of cellular biochemistry and processes - and the tools to take advantage of this knowledge. These developments will enable and blend into the emergence of advanced medical nanotechnology ... and things will get interesting thereafter.


The Aging Immune System

The open access journal Immunity and Ageing has a pair of review and commentary papers on the front page at the moment. Take a look:

Melatonin, Immune Function and Aging:

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infections and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. ... Circulating melatonin decreases with age and in recent years much interest has been focussed on its immunomodulatory effect.

Immunosenescence and Vaccination:

The problems associated with the ageing immune system and vaccination were discussed recently at an international workshop at the Jenner Institute for Vaccine Research, Compton, UK, 6-7 October, 2005. This is a commentary on that session. The meeting included discussions on T and B cell differentiation and ageing, as well as dendritic cell and neutrophil data, with the emphasis on T cell immunosenescence, perceived as the most important hindrance to satisfactory responses to vaccines in the elderly. The main questions to be addressed in this context are the reasons for dysfunctionality of T cells in the elderly and what to do to improve T cell function.

A lot of things go south when the immune system starts to fail under the burden of accumulated age-related damage. Over the long term, we can hope that present work on a range of immune therapies and stem cell medicine provides a far greater understanding of the immune system - leading to the ability to repair or prevent age-related damage. If you want to extend the life span of a complex machine, you certainly have to extend the life span of the components.

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Civilization And Longevity

(From Tech Central Station). The history of civilization can in many ways be viewed as the history of increasing longevity. While historical increases in life expectancy occurred for reasons that have little to do with how biotechnology will lead to radical life extension in the future, it is still informative to look at the big picture: "The life expectancy, if I can go back to 1700, was only about 35 years at birth. In 1900, 200 years later, it had increased by about 12 years - it was in the neighborhood of 47 in Western European countries. And, today it's 77 or 78, so in a century we added 30 years to life expectancy, maybe a little bit more. ... Public health reform, cleaning up of the water supply, cleaning up of the milk supply. But if you said what was the single most important factor, it's technological change."