Fight Aging!

The Methuselah Foundation, founded back in 2003, aims to promote and support scientific progress towards defeating age-related disease, repairing the damage of aging, and greatly extending the healthy human life span. To that end the Foundation has raised more than $10 million in funding pledges, and their initiatives include the Mprize for longevity science, the recently launched NewOrgan Prize, investment in tissue engineering startups such as Organovo, and - prior to the establishment of the SENS Foundation as a separate entity - the funding of Aubrey de Grey's research program for rejuvenation biotechnology.

These activities, and the networking to support them behind the scenes, have had a great impact upon the state of the aging research community, media treatment of longevity science, and public perception of the plausibility of medical research aimed at reversing aging. Thanks to the efforts of the Foundation volunteers and thousands of supporters, the environment for longevity science today is far improved over that of ten years ago. That in turn means that our chances of seeing working rejuvenation medicine within our lifetimes are also improved.

When you stop to think about it, there is no more important work a person could be undertaking in this day and age. What else could you possibly find to do that will save as many lives and change the world for the better as greatly? This is the age of biotechnology, and there is no higher use for biotechnology than to grant everyone more youth, more life, more health, more vigor.

As some of you may know, I have volunteered with the Methuselah Foundation as a technical resource for a while now. A brief inspection of the website will tell you that the Foundation runs on a LAMP stack - Linux, Apache, MySQL, and PHP. What you won't see is the largely invisible bulk of packaged code, integrations, mail, archives, and other systems required to run a distributed volunteer non-profit organization. Add that to the newer online projects in the works or on the drawing board, and keeping things running as well as moving forward begins to require a considerable amount of time from people who know how to code or maintain a server.

Sadly, I have less time to give to the Foundation at present than I have in the past - and fully recognize the irony of this state of affairs, given my comments on importance above. From a practical standpoint, this means is that the Foundation needs a reliable, smart volunteer programmer: someone who is comfortable building their own websites from scratch, working independently as a part of a geographically distributed team, can contribute to the process of developing plans and designs, and confidently touch every part of the LAMP stack in the doing of it.

That said, reliability is the key, central value needed for a technical volunteer. In any non-profit, volunteers come and volunteers go, but it is very challenging to find people who follow through on a commitment to stay for a given project, or to act as support for a non-profit site for the necessary months and years to build up familiarity with the systems used. When it comes to technology, those rare few are absolutely necessary, however - you simply can't run a tight ship if developers flake out on a regular basis. This is especially true when it comes to projects wherein the team is scattered across the US or the world, and rarely meets in person.

But the open source community has plenty of experience with these issues, and there are some great teams out there - hundreds or thousands of developers willing to put in time over the long term to help advance good causes with their skills.

If you think you can be the reliable, tech-savvy volunteer needed here - someone who can help me keep the Foundation technology running, and build the new initiatives that are the best foot forward for longevity science advocacy in the 2010s - then you should head on over to the Methuselah Foundation website and send them an email.

A response to recent arguments on the biological basis for women's longevity advantage: "The most influential line of reasoning in gerontology is known as Disposable Soma Theory (DST). In brief, the theory states that aging is caused by accumulation of random damage, which is counteracted by repair. Repair is costly and the organism allocates exactly the needed amount of energetic resources. Recently, DST was applied to explain why women live longer than men. Women are less disposable than men, so they need a better repair and thus live longer. It might seem slightly repetitive that women live longer because they are less disposable because females need better health for reproduction. I will discuss that this explanation is also erroneous. But to start with, the name of the theory (disposable soma) is ambiguous because soma is disposable by definition: soma versus germ line. All theories of aging are more or less disposable soma theories. ... The question is why is soma disposable and what makes it disposable. According to DST, it is allocation of resources from repair to other needs. Here we will discuss drastically different cause. ... So why do women live longer? ... In brief, high accidental death rate is associated with faster aging in different species, from worms to mammals. The same is applicable to longevity of males versus females. The accidental death rate, from accidents, violence, combat, is higher in young men than in women. Historically, it was much higher. Higher accidental death rate in young men may have led them to be larger and stronger than women. ... mTOR drives cellular size growth and muscle hypertrophy, including testosterone-induced hypertrophy ... I suggest that hyper-active mTOR contributes to physical robustness of young males, allowing them to fight and compete. But hyper-active mTOR is beneficial earlier in life at the cost of accelerated aging. ... In other words, accelerated aging in males relative to females could be a byproduct of physical robustness to prevent death from extrinsic causes." As you can see there is still plenty of room for debate in even apparently simple, straightforward questions in aging science.

Link: http://www.impactaging.com/papers/v2/n12/full/100253.html

A recent review: "It has been almost two decades since dietary restriction was first shown to increase Drosophila lifespan. Since then, understanding this phenomenon advanced as groups worked to identify what quality of restricted diet matters: calories or a specific nutrient. The problem is complex because is it difficult to measure what a fly actually consumes. A powerful solution uses the geometric framework of nutrition where diets in many combinations can be tested for their effects on lifespan and reproduction while measuring intake. Applied to Drosophila, it is now clear that specific nutrients, not calories, mediate longevity. The geometric framework also reveals a nutritional basis for the trade-off between reproduction and lifespan. This complements a stable isotope analysis that tracked the allocation of nitrogen, carbon and essential amino acids into eggs versus reproduction. Together these studies show this is not possible to explain how DR extends lifespan through a mechanism were resources are simply reallocated to somatic maintenance away from reproduction. Although promising in principle, genetic analysis of DR mechanisms has had limited success. To be productive studies must include enough diets at appropriate concentrations. In reviewing the best data, there is little evidence to date for any gene to be required for DR to increase Drosophila lifespan [as opposed to the situation in nematode worms], including insulin signaling or 4eBP. Strong analyses of genes required for DR should be a priority in future research with Drosophila and this may be made most robust by considering the effect of mutants in the context of the geometric framework."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21187139

Biotechnology these days mimics the computing hardware industry: some areas are moving with blazing speed, making other fields that are only progressing rapidly seem slow in comparison. Costs of tools and procedures are falling rapidly, whilst reliability and capabilities are improving by leaps and bounds. The bulky, lab-bound machineries of ten years ago are becoming desktop machines now, and by 2020 they will be hand-held devices that cost little more than a pricey smartphone does today. (By 2020, smartphones of that capacity will be next to free, and what you carry around in your pocket will have more processing power than one of today's high-end rack mount servers).

As an illustration:

The Personal Genome Machine (PGM) by Ion Torrent is a DIY biologist's fantasy: it's fast, compact, and the first sequencer to come even close to commercial viability. Hell, it even has an iPod dock. ... The PGM is their contribution to the growing commercial genomics marketplace, and a powerful reminder of how sequencing tech is following Moore's Law. It will set you back $49,500, [which] still keeps it out of reach for all but the most affluent DIYers. Still, at less than 1/10th the price of competing sequencers (compare it against PacBio's system at $695k), don't be surprised if it starts making headway into research labs.

It wasn't all that long ago that you'd be forking over millions of dollars for a DNA sequencing machine that was far less useful than those on the market today, and certainly a good deal more bulky and failure-prone. This is what a less regulated field of development looks like - its participants rapidly produce tremendous benefits for their customers as a consequence of aggressive, constant competition over price and features. That requires the freedom for new entrants to jump into development and try their ideas without approval from government or other higher powers, something that is sadly lacking in medicine beyond the fast-moving fields like DNA sequencing.

Long term projections of life span continue to trend upward as the actuaries revise their opinions on biotechnology - but I believe they still fail to account for potential revolutionary advances in medicine that lie ahead. The level of uncertainty at least is fairly well grasped now within the actuarial industry, but for various political reasons it is only slowly seeping into official projections: "In the first official projection of its kind, the Department for Work and Pensions today forecasts that almost a fifth of Britons will celebrate their 100th birthday. Of the 17 per cent of the population who will become centenarians, about three million are under the age of 16, and 5.5 million are aged between 16 and 50. In total, about half a million people a year will be celebrating their 100th birthday by 2066, compared with about 10,000 now. Nearly 8,000 of them will reach their 110th birthday. ... Predicting the rate of increase of life expectancy used to be much easier because the rate of increase did not vary much. But some areas of biotechnology are increasingly driven by the same kinds of advances that make computer power increase so rapidly. ... It is difficult to look down the road 20 years and guess every way that biological manipulations will speed up by orders of magnitude or which treatments will become very easy as a consequence. But it seems reasonable to expect that in the 21st century we will experience a revolution in biotechnology in par with the revolution in computer technology that began in the middle of the 20th century and continues to this day." Retirement as an institution will radically change, and those countries that practice the iniquity of forcing people out of work at a certain age will also have to change.

Link: http://www.futurepundit.com/archives/007788.html

This study looks for measures that might reflect rates at which new medical technology makes its way into the marketplace, and checks for correlation with rising life expectancy. The result is what you might expect - that more rapid adoption of new technology means longer lives: "The rate of increase of longevity has varied considerably across U.S. states since 1991. This paper examines the effect of the quality of medical care, behavioral risk factors (obesity, smoking, and AIDS incidence), and other variables (education, income, and health insurance coverage) on life expectancy and medical expenditure using longitudinal state-level data. We examine the effects of three different measures of the quality of medical care. The first is the average quality of diagnostic imaging procedures, defined as the fraction of procedures that are advanced procedures. The second is the average quality of practicing physicians, defined as the fraction of physicians that were trained at top-ranked medical schools. The third is the mean vintage (FDA approval year) of outpatient and inpatient prescription drugs. Life expectancy increased more rapidly in states where (1) the fraction of Medicare diagnostic imaging procedures that were advanced procedures increased more rapidly; (2) the vintage of self- and provider-administered drugs increased more rapidly; and (3) the quality of medical schools previously attended by physicians increased more rapidly. States with larger increases in the quality of diagnostic procedures, drugs, and physicians did not have larger increases in per capita medical expenditure. We perform several tests of the robustness of the life expectancy model. Controlling for per capita health expenditure (the 'quantity' of healthcare), and eliminating the influence of infant mortality, has virtually no effect on the healthcare quality coefficients. Controlling for the adoption of an important nonmedical innovation also has little influence on the estimated effects of medical innovation adoption on life expectancy."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21188512

There is a discussion that takes place with great regularity within any community of advocates. It builds from the eternal triad: (a) exceedingly wealthy people exist, (b) their wealth could change the world for the better if applied in the right way, and yet (c) they are not applying their wealth in this right way. Pick your "right way" from any of the paths you consider valuable - for me, it's generating meaningful progress towards the prevention and reversal of degenerative aging, the universal medical condition that kills more than 100,000 people every day. But perhaps you have something better, more beneficial to humanity in mind. After all, we're all very sure of the causes we support.

Some folk seem to thrive on the outrage they can generate by considering just how many dollars of other people's money aren't being spent the way they want. Others are deeply saddened and discouraged - but neither strikes me as a healthy way to view the world. Why should an advocate be perpetually worked up about those wealthy individuals who do not see the world the same way as he or she does? Perhaps because the advocate expects more from the wealthy than from the poor - and in many more ways than relate to size of donation.

What I mean by this is that I think there's a certain tendency to believe that wealthy people have attributes and talents that in fact they don't possess: they have a great deal of one important thing, so therefore they must have more of all the others, right? But across a broad spectrum of the wealthy, you are probably not going to see greater intelligence, drive, wit ... or vision. Wealth doesn't grant you any of these things if you didn't have them beforehand, and a few decades of being alive and socially active should teach you that none are a necessary prerequisite for becoming wealthy. I'm not even all that certain that they help.

If you think over your experiences in talking about longevity science with people, you're probably in just the same boat as me: most of the folk you'll meet don't believe that near-term progress is possible, don't like to think about aging and death anyway, and are locked into a view of their own lives that has them progressing and ending just like those of their grandparents. There is no vision, they learned the shape of the box they will live in while they were young and in school, and have little interest in change. In this, your friends and acquaintances are not at all different from any given selection of high net worth individuals.

So why be disappointed that those high net worth individuals are just as unlikely to help of their own accord, or understand the possible future of rejuvenation biotechnology? Wealth is not magic gold and blessings from the fae; these people grew up in the same society as the rest of us, and thus are on average just as blinkered - in need of education and persuasion - when it comes to aging and longevity science.

Now with all that said, you might look at Maria Konovalenko's comments on the philanthropic works of Bill Gates:

Mr. Gates said: "No idea is too radical" in what he termed as the Grand Challenges in Global Health and the goal was to pursue paths that the National Institutes of Health and other grant makers could not. Based on these statements in the article, we can see that the money has not been spent effectively so far. As life extension specialists, gerontologist and on behalf of all humanity - we are urging you to help pursue an expansion into anti-aging research.

To the best of my knowledge, the Gates Foundation makes no significant contributions towards longevity science - which one would presume means that Bill Gates and his advisors are average, ordinary folk in that regard. Unconvinced, or it isn't even on their mental radar, or they are set comfortably into the scope of a life they believe will look like that of their grandparents. And so forth. It is a challenge: exactly the same challenge that you yourself have faced when you have trouble persuading a friend on the development of rejuvenation biotechnologies and support of the SENS Foundation.

Failing grip strength in older people is a good biomarker for frailty in all bodily systems and consequently higher mortality levels. Separately, advanced glycation end-products (AGEs) accumulate in the body's tissues with age, and impact a number of important biological processes - so we'd expect to see correlation between rising AGE levels and failing grip strength even if they have no direct link and are completely distinct aspects of age-related degeneration. Here, researchers show that this correlation stretches back into earlier adult life: "Aging is associated with decreased skeletal muscle function. Increased levels of advanced glycation end products (AGEs) in skeletal muscle tissue are observed with advancing age and in diabetes. Although serum AGE level is negatively associated with grip strength in elderly people, it is unknown whether this association is present in adult males. To determine the relationship between AGE accumulation in tissue and muscle strength and power among Japanese adult men. Skin autofluorescence (AF) (a noninvasive method for measuring tissue AGEs), grip strength, and leg extension power were measured in Japanese adult men ... Among Japanese adult men, participants with higher skin AF had lower muscle strength and power, indicating a relationship between AGE accumulation and muscle strength and power. A long-term prospective study is required to clarify the causality." If forced to guess, I'd suggest that the other biochemical and cellular causes of aging have a greater impact than AGEs on muscle strength - but that remains to be established, and we should still be trying to fix everything regardless of the outcome of that investigation.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21188413

The cellular recycling process of autophagy appears to be important in many of the known methods of slowing aging through manipulation of metabolism. AMPK is a protein involved in the control of metabolism that is important and of interest in aging research, and this may be because of its influence over autophagy: researchers "have discovered how AMPK, a metabolic master switch that springs into gear when cells run low on energy, revs up a cellular recycling program to free up essential molecular building blocks in times of need. ... AMPK activates a cellular recycling process known as autophagy by activating an enzyme known as ATG1, that jumpstarts the process. The newly uncovered direct molecular connection between AMPK and ATG1 is significant because dysfunctions in both AMPK signaling and autophagy are implicated in a plethora of aging-related diseases, including type II diabetes, cancer, and neurodegenerative diseases such Parkinson's and Alzheimers. ... the group focused on large intracellular structures called mitochondria, whose role is to generate energy. ... Mitochondria are easily damaged in detoxifying tissues like liver. A critical way that defective mitochondria are turned over is through a special form of autophagy called mitophagy. ... In that case, cells would envelope their unhealthy mitochondria in a membrane, dump them in a cellular acid pit, and recycle the remains. If AMPK initiated the process, cells genetically engineered to lack AMPK might show altered mitochondrial turnover compared to normal cells. And that is precisely what the researchers saw: liver cells in which AMPK had been eliminated contained too many mitochondria, many of which looked spindly, indicating they were moribund, and confirming that AMPK was directing autophagic waste disposal."

Link: http://www.eurekalert.org/pub_releases/2010-12/si-hc122010.php

The present fundraising initiative at the Immortality Institute is another in their series of small research projects that can, despite their modest price tag, contribute to progress in longevity and aging science:

Cognitive functions of the brain decline with age. One of the protective cell types in the brain are called microglia cells. However, these microglia cells also loose function with age. Our aim is to replace non-functional microglia with new and young microglia cells derived from adult stem cells.

We will inject these young microglia cells into 'Alzheimer mice' - a model for Alzheimers disease. After giving the cells some time to work, we will sacrifice the mice and measure microglia activity, neurogenesis, proliferation of neuroprogenitors and plaque density in the brain. A reduction in plaque density of Alzheimer mice would be a first proof that the transplanted microglia are performing their expected function.

The full PDF format research proposal is available: the work will be carried out by a graduate research assistant and will cost $16,000. This is the essence of our present era of biotechnology: a task that would have occupied a whole laboratory and its equipment in the 1980s, and cost a great deal of money if it was even possible at all, is now something that a skilled graduate-level life scientist can organize and run himself within an established lab. The times are changing - and this plummeting cost of research will only continue.

As I pointed out previously, this breaking down of the priesthood through lowered barriers to entry is how open source development has greatly advanced software development. It will do the same for biotechnology - hard problems requiring large investments in knowledge and resources will still typically be solved by scientific professionals working in traditional organizations, but they won't waste their time working on the easier issues. The much larger number of citizen scientists will be rapidly organizing to accomplish everything they are capable of and freely sharing the results of their work.

One benefit that truly stands out in this future is that research projects ignored by mainstream funding organizations stand a strong chance of making headway. One such presently ignored project is serious anti-aging research, work to find ways to prevent and reverse age-related damage - and soon. As biotech advances and computers become more capable, we activists are going to move from talking, educating and raising money to all that plus performing scientific research using the tools of open source biotechnology.

For this microglia transplant research, the Immortality Institute will put forward $8,000 of its own funds to match another $8,000 in donations to meet the project cost: volunteers have so far raised $1,700. So as the year comes to a close, why not step in and help out here? You'll be in good company; I just pitched in another $200 for the pot.

A range of biological differences have been noted that distinguish exceptionally long-lived families from the rest of us poor mortals. Here is another: "The development of medical interventions for the preservation of disease-free longevity would be facilitated by markers that predict healthy aging. Altered protein N-glycosylation patterns have been found with increasing age and several disease states. Here we investigate whether glycans derived from the total glycoprotein pool in plasma mark familial longevity and distinguish healthy from unhealthy aging. Total plasma N-glycan profiles of 2396 middle aged participants in the Leiden Longevity Study (LLS) were obtained... After normalization and batch correction, several regression strategies were applied to evaluate associations between glycan patterns, familial longevity and healthy aging. Two N-glycan features (LC-7 and LC-8) were identified to be more abundant in plasma of the offspring of long-lived individuals as compared to controls. ... Furthermore, a decrease in levels of LC-8 was associated with the occurrence of myocardial infarction, indicating that plasma glycosylation patterns do not only mark familial longevity, but may also reflect healthy aging. In conclusion, we describe two glycan features, of which increased levels mark familial longevity while decreased levels of one of these features mark the presence of cardiovascular disease."

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

From Michael Batin, and machine-translated: "For the Foundation Science for Life Extension, the main outcome [for this past year] was the first Russian unique operation on transplantation of the trachea, grown from [the patient's own stem cells]. Operation using the method of Professor Paolo Macchiarini held in December in Research Center of Surgery named after Academician BV Petrovsky, RAMS (Moscow). In order to bring this technique to Russia, the Foundation has worked a half years. We fully fund the project and organize the interaction of all participants - RAMS RNTSH, Clinics Karredzhi University of Florence, pharmaceutical companies, manufacturers of biomaterials. Total project costs amounted to around 250 thousand euros. ... Patient was a 26-year-old girl. In 2006, she was hit by a car, she was very seriously injured, survived clinical death, a few months has been in a coma. Breathe on their own she could not ... Now the patient before discharge - she can speak much better breathing, can walk and perform physical activity. ... This operation - the beginning of the introduction into clinical practice of regenerative medicine technologies, which opens up broad prospects for the treatment of serious illnesses associated with the loss of vital organs and tissues, and allows scientific and clinical institutions of Russia to enter the International Consortium for Regenerative Medicine." The process used here is decellularization, in which a donor trachea is stripped of its cells, leaving only the structure of the extracellular matrix. That is then repopulated with the patient's own cells, which avoids the normal issues of transplant rejection.

Link: http://translate.google.com/translate?hl=en&sl=auto&tl=en&u=http://m-batin.livejournal.com/96309.html

It is fairly easy to slide from the question "why live longer?" to the question "why live?" If you're not so sold on being alive at the present time, it may follow that you're also not so much in favor of being alive for longer in the future. Sadly, many people are on the fence when it comes to their continued existence as thinking, conscious entities: ambivalent until threatened with impending death, at which point deep-seated survival instincts take over, but ultimately vaguely looking forward to their end. Others call into question the morality of creating new people when they are doomed to inevitable suffering and death, and this cheerful topic leads us to a brace of posts at Depressed Metabolism.

Non-existence is hard to do

Even the antinatalist position that it is better never to have been and that we have a moral obligation not to procreate is not completely obscure. Who has not had the experience of talking to the grumpy old lady who wonders why anyone would want to bring children into this world? We routinely dismiss such positions as being out of touch with reality but modern culture persists in linking intellectualism to pessimism.

Review of 'Better Never to Have Been'

"Would that I had never been born" is a lament sometimes voiced in the depth of misfortune, a cry of despair we hope may be soon be stilled by something more positive, when the bad things, whatever they are, have run their course. Enter David Benatar, a respected professor of philosophy at the University of Cape Town, South Africa. In the volume here reviewed he offers the extreme view that in fact it would have been better, all things considered, if not one of us had ever existed, or even any sentient life whatever. Life is that bad, he says, and he bases this judgment on certain logical principles along with empirical evidence of the allegedly poor quality of life that most of us are forced to endure in this world. Among the consequences is that no more humans should be born, and the human race (and other sentient creatures) ought to become extinct.

Is a life worth starting? Some personal views

Life does, of course, have its problems, death in particular, that might call in question whether it is worthwhile after all and thus, whether the life of any sentient being is worth starting. For this one problem there are a number of possible answers that will be satisfying to different people, and thus can serve as ground for a feeling that life is worthwhile and was worth starting despite one's own mortality. There is the famous Epicurean argument that death is not really a problem because before it happens it causes no harm, and after it happens there is no victim. ... Then there is scientific immortalism, which holds that at least substantial life extension through science and technology is possible, so that, irrespective of any supernatural or mystical process, persons of today have more to hope for as they get older than the usual biological ruin and oblivion.

Engineered human longevity as a bright view into the future of freedom from pain, rejuvenation, the triumph of life, and agelessness is forever wedded to to the flip side of the coin, which is that people suffer and people die. No-one wants to think about death, but that fact doesn't make it any less real or any less a threat. Nor does it dispel those elements of our culture who greatly value death, or who believe that people should be forced to age to death rather than take advantage of the coming age of longevity science. They exist, and they are playing in the great game of accomplishment and persuasion just like the rest of us - we ignore them at our peril.

Researchers look for root causes of the longevity enhancement produced by eliminating the male contribution to the mouse genome: "A recent study by Kawahara and Kono (2010) reports that mice artificially produced with two sets of female genomes have an increased average lifespan of 28%. Moreover, these animals exhibit a smaller body size, a trait also observed in several other long-lived mouse models. One hypothesis is that alterations in the expression of paternally methylated imprinted genes are responsible for the life-extension of bi-maternal mice. Considering the similarities in postnatal growth retardation between mice with mutations in the Rasgrf1 imprinted gene and bi-maternal mice, Rasgrf1 is the most likely culprit for the low body weight and extended lifespan of bi-maternal mice. Rasgrf1 is a neuronal guanine-nucleotide exchange factor that induces Ras signaling in a calcium-dependent manner and has been implicated in learning and memory. Like other long-lived mouse strains, Rasgrf1 mutants are known to have low growth hormone and IGF-1 levels and the Rasgrf1 yeast homolog CDC25 had been previously associated with lifespan. Therefore, although the evidence is not conclusive, it does point towards the involvement of Rasgrf1 in the regulation of longevity, hypothetically through a mechanism similar to that observed in other long-lived mice of low GH/IGF-1 signaling causing a low body weight and life-extension."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21182853

One view of strategy in the development of calorie restriction mimetic treatments: "Calorie restriction (CR) remains the most robust environmental intervention for altering aging processes and increasing healthspan and lifespan. Emerging from progress made in many nonhuman models, current research has expanded to formal, controlled human studies of CR. Since long-term CR requires a major commitment of will power and long-term negative consequences remain to be determined, the concept of a calorie restriction mimetic (CRM) has become a new area of investigation within gerontology. We have proposed that a CRM is a compound that mimics metabolic, hormonal, and physiological effects of CR, activates stress response pathways observed in CR and enhances stress protection, produces CR-like effects on longevity, reduces age-related disease, and maintains more youthful function, all without significantly reducing food intake. Over 12 years ago, we introduced the concept of glycolytic inhibition as a strategy for developing mimetics of CR. We have argued that inhibiting energy utilization as far upstream as possible might offer a broader range of CR-like effects as opposed to targeting a singular molecular target downstream. As the first candidate CRM, 2-deoxyglucose, a known anti-glycolytic, provided a remarkable phenotype of CR, but turned out to produce cardiotoxicity in rats. Since the introduction of 2DG as a candidate CRM, many different targets for development have now been proposed at more downstream sites, including insulin receptor sensitizers, sirtuin activators, and inhibitors of mTOR."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21167272

A letter from Dave Gobel, founder of the Methuselah Foundation:

For the price of a cup of coffee per day, would you like to join a select group of humanitarians who will be remembered for their vision and saving millions of lives?

Modern medical science continues to show us that the aging process may no longer be the intractable problem it has been perceived to be for every generation preceding ours. There is a present need to move faster towards a previously unattainable goal: the control of aging. This need for more rapid medical progess is only magnified by the current profound lack of funding for aging research. Funding springs, at root, from widespread public awareness of advances and possibilities in aging research. Educating the public is an essential step in moving philanthropists and governments to allocate more resources to the study of aging. The problems caused by aging leave us poor in body, spirit, and finances. We must step forward to tackle them!

The Mprize for longevity research is working hard to build public interest and has had some considerable success, raising more than $4 million in total pledges since its launch in 2003. Encouraged by these results and knowing that the size of the fund is directly related to its effectiveness as a publicity tool, we continue to push forward with a fundraising project that we feel will fit the circumstance. You might be interested in this initiative.

We call it "The Three Hundred" ... themed from history and limited to that number of participants. These individuals (or organizations) see the potential of the Mprize and believe that aging can be defeated. Members of The Three Hundred have made a commitment to creating a better future, one in which the suffering caused by aging is greatly diminished or banished entirely. The unique foresight shared by The Three Hundred at this early stage in aging research will be remembered - they grasped the ring, heard the call and took action when the opportunity first presented itself. The efforts of the Three Hundred will be remembered, like those of their historical counterparts, far into the future.

The existence of The Three Hundred resonates with those who feel the injustice of the aging process, people who welcome the first serious attempts in human history to fight aging and win. Nine enthusiastic individuals signed up before we could even make the announcement public, and more than a hundred have stepped forward to join as of the first day of 2007. Please visit our website and read about The Three Hundred:

http://www.mfoundation.org/?pn=mj_donations_the300

The control of aging is forseeable. Science provides the tools, researchers provide the labor, the Mprize will provide the funding. Please consider joining our effort to create a better, longer, healthier future.

What's it worth to you to live 150 healthy years? What's it worth to you to raise the average human lifespan to 150 years, just as a start? These are not idle questions! Membership of The Three Hundred is a meaningful but affordable commitment: $1,000 a year, by the end of each year, for 25 years. This amounts to $85 a month or $2.75 a day, the equivalent of a visit to Starbucks.

The Three Hundred is a classical concept, based on a battle that saved the future of Western Civilization: Thermopylae. In 480 B.C., 300 Spartan warriors fought against incredible odds to gain time for the rest of Greece to mobilize against the Persian hordes. Without the delaying action fought at the narrow pass of Thermopylae, the achievements of Greece and our culture as we know it would have been swept away.

The Methuselah Foundation is asking you to follow in the footsteps of this noble Three Hundred, not to risk your lives, but to provide some of your treasure so that we can all live ... and live ... and live. You will help to win time for the human species to beat back an enemy far more dangerous than the ancient Persians: the Grim Reaper himself.

The Three Hundred - a group strictly limited to 300 members - will live on in history, as the Three Hundred of Thermopylae are remembered even to this day. You can be one of them. The names of the 300 Spartans who fought at Thermopylae were engraved on a stone tablet in Sparta that was still legible seven centuries later. A momument stands to this day to pay homage to their sacrifice. In lending your name to this enterprise, you will be remembered for as long as the human race survives.

We have reached a potential tipping point in human history: a time in which the quest to extend the healthy human life span can be taken seriously and extensive resources devoted to understand and defeat the aging process. The pledges of the Three Hundred will help further large sums to be raised for Foundation projects such as the Mprize for longevity research.

I am a member of the Three Hundred, and I have put my money where my mouth is. To become one of the Three Hundred is to take the initiative, to recognize that our contributions will make an ever-growing difference to the future of medical research, health and longevity. We are the rainmakers, the pebbles who trigger the avalanche, the first to heed the call. By our actions, we lead the way and will long be remembered for it.

Think deeply, follow my lead, and join the Three Hundred. Take part in the fight to cure aging!

Well now, this is interesting:

The Board of Directors of Alcor Life Extension Foundation today announced that Dr. Max More, 46, has been named Chief Executive Officer effective Jan 1, 2011.

...

"Max brings a quarter century of experience in and commitment to cryopreservation, life extension, and improving the future," said Alcor director Tim Shavers, "and has earned a reputation for both practical and principled leadership and bold thinking. Crucially, he shares our vision of Alcor's mission and understands the organization's past and its challenges and opportunities. His extensive knowledge of our operations, goals, and needs makes him the ideal choice to lead Alcor as CEO," said Shavers.

If you want to learn more about Max More, you should browse his website. More might be considered one of the founding members of the modern transhumanist community, with a long running interest in engineering greater human longevity. He is the author of the Extropian Principles, amongst numerous other works, a vision of open societies working to transcend the limits of our evolved biology through research and development of new technologies:

Like humanists, transhumanists favor reason, progress, and values centered on our well being rather than on an external religious authority. Transhumanists take humanism further by challenging human limits by means of science and technology combined with critical and creative thinking. We challenge the inevitability of aging and death, and we seek continuing enhancements to our intellectual abilities, our physical capacities, and our emotional development. We see humanity as a transitory stage in the evolutionary development of intelligence. We advocate using science to accelerate our move from human to a transhuman or posthuman condition. As physicist Freeman Dyson has said: "Humanity looks to me like a magnificent beginning but not the final word."

Overall, this an excellent piece of news to brighten the day before Christmas. As I remarked when the last outside CEO departed:

I'm sorry to see Joe Waynick move on: I have long said that a more professional, business-oriented hand on the wheel would help Alcor make the jump to the next level. In order to provide cryonics services to a greater number of people, Alcor simply has to grow, become more professional, diversify their technologies into other profitable outlets - doing all the things that any business must do as it moves forward to greater success. To my eyes, Waynick brought a necessary mindset to the job; I hope that his replacement will be looking to the same future, as it seems that Alcor still has a way to go.

A related topic: lurking somewhere in my shadowy list of things to write about are a range of thoughts on when a supporter of engineered longevity should rationally switch their efforts away from biotechnology to focus on cryonics. At some point, if biotechnology is not advancing rapidly enough, your evolving best guess at the future will be that you will miss the boat. If that is your belief, then working on cryonics is your best option to avoid destruction of the self and oblivion. For me, I think that point is some years out yet, but I'll certainly be putting a lot of thought into it come 2020.

On the one hand, people tend to greatly overestimate how much can be accomplished in a decade, while greatly underestimating what can be accomplished in 20 years. On the other hand, time is fleeting, and the regulatory embrace that squashes people's ability to bring new technologies to market is only getting worse. But I can wait a decade before thinking seriously about changing roads. For more of my thoughts on timing, you might look back into the Fight Aging! archives:

• Three Decades From Now
• Timelines For Agelessness Through Medical Technology
• Will The Biomedical Technologies of 2030 Grant Another 20 Years of Life?
• A Different View of Where We'll All Be Around About 2030
• The Million Year Lifespan

The mainstream biogerontology community is engaged in the very, very long and complex process of unpicking all of the detailed changes in biological signaling pathways that occur with aging. The starting points are identified metabolic changes that accompany treatments, lifestyle choices, or environmental circumstances known to extend life. The end result is to fully understand why these low-level biochemical changes lead to longer life span, and replicate or better them. This is a very long term project, which is why many of these researchers do not expect meaningful artificial extension of human life span within their lifetimes, even allowing for accelerating growth in biotechnology and computing power. This article is an example of this sort of research: "researchers have linked hyperactivity in the [mammalian] target of rapamycin complex 1 (mTORC1) cellular pathway to reduced ketone production in the liver, which is a well-defined physiological trait of aging in mice. During sleep or other times of low carbohydrate intake, such as fasting or periods of dieting, the liver converts fatty acids to ketones, which are vital sources of energy during fasting, especially for the heart and brain. As animals age, their ability to produce ketones in response to fasting declines. ... This is the first time that the mTORC1 pathway has been shown to affect a trait associated with aging. This discovery will enable researchers to study the aging process in greater detail, helping them to determine how and why aging suppresses ketone production and activates mTORC1."

Link: http://www.newswise.com/articles/view/571937/

It should not be a surprise to see suppression of growth hormone in mammals result in extended healthy life spans. After all, the present record holder for the Mprize for mouse longevity involved gene engineering of a growth hormone deficient breed. Here researchers demonstrate benefits in a mouse breed used for Alzheimer's research, as it develops accelerated degeneration of the brain: "people sometimes take growth hormone, believing it will be the fountain of youth. ... Many older people have been taking growth hormone to rejuvenate themselves. These results strongly suggest that growth hormone, when given to middle aged and older people, may be hazardous. ... The scientists studied the compound MZ-5-156, a 'growth hormone-releasing hormone (GHRH) antagonist.' They conducted their research in the SAMP8 mouse model, a strain engineered for studies of the aging process. Overall, the researchers found that MZ-5-156 had positive effects on oxidative stress in the brain, improving cognition, telomerase activity (the actions of an enzyme which protects DNA material) and life span, while decreasing tumor activity. MZ-5-156, like many GHRH antagonists, inhibited several human cancers, including prostate, breast, brain and lung cancers. It also had positive effects on learning, and is linked to improvements in short-term memory. The antioxidant actions led to less oxidative stress, reversing cognitive impairment in the aging mouse."

Link: http://www.physorg.com/news/2010-12-un-growth-hormone-longevity.html

Calorie restriction and exercise improve health and longevity to some degree in humans, which makes them topics of interest for the mainstream of aging research - scientists focused on finding ways to permanently adjust human metabolism to slow the damage of aging. Just as investigations into the biochemistry of calorie restriction have produced a field of research aimed at producing calorie restriction mimetics, so too will a greater understanding of the effects of exercise lead into the development of exercise mimetics.

The driving idea here is that people will pay for medical technologies that provide some of the benefits of calorie restriction or exercise without the need for the hard work and willpower involved in the real thing. This seems like a reasonable conjecture, and so plenty of money is flowing into research and development for calorie restriction and exercise mimetic drugs. Where this research starts is the search for genes or proteins that can be manipulated to trigger some of the specific, measurable health or longevity benefits resulting from these lifestyle choices. For example:

Gene alteration in mice mimics heart-building effect of exercise:

By tweaking a single gene, scientists have mimicked in sedentary mice the heart-strengthening effects of two weeks of endurance training ... The genetic manipulation spurred the animals' heart muscle cells - called cardiomyocytes - to proliferate and grow larger by an amount comparable to normal mice that swam for up to three hours a day

...

First, they had adult mice swim daily for increasing amounts of time, and after 14 days found that their hearts were mildly enlarged as a result. Other mice with restricted blood flow in their aorta also showed enlargement, but of the type associated with heart disease. The researchers then screened both sets of animals against a collection of all known transcription factors -- proteins that turn gene activity up or down -- and compared their expression in the two types of heart enlargement.

The key differences turned out to be in a pair of transcription factors acting in concert. One, C/EPB-beta, had reduced activity in the exercised mice while the other, CITED4, was more active.

So, could turning down C/EPB-beta in normal mice cause their hearts to grow as if they had been working out - even though they did no extra exercise? The answer was yes: Genetic manipulation to reduce C/EPB-beta expression raised the activity of CITED4, and in those mice, cardiomyocytes began dividing and growing in size until their heart muscles resembled those of the endurance swimmers. The mice also had markedly improved maximal exercise capacity even without exercise training.

Genes produce proteins through the process of gene expression, and the effects of changing the level of expression via genetic engineering can be replicated using designed molecules in a number of different ways. So the next step is typically to seek funding in order to design and test a molecule that can reproduce the observed benefits, and which will later become a drug candidate if successful.

Singularity Hub looks at the some of the work of mainstream gerontology: "Researchers are working diligently to address the seemingly unavoidable realities of aging and dying. In fact, the University of Southern California founded the Davis School of Gerontology for such a purpose, and the institute serves as the oldest and largest institute of its kind. .. Faculty at the Davis School of Gerontology have adopted a multi-pronged approach to the problem and are pursuing various avenues that may lead to a solution. Caleb "Tuck" Finch and his colleagues have been investigating the interaction between inflammation and the aging process. He posits that postnatal factors such as environmental pollution and diet may exert aging effects through inflammation pathways. He also investigates the role hormones may have on the aging process, observing how changes in sex hormones late in life could mediate neural senescence. Generally, he is optimistic about treating the neurodegenerative diseases of aging, believing we'll be able to lower the risk of Alzheimer's and control its course by the next decade ... Another faculty member, Dr. Valter Longo, extended the lifespan of yeast 10 times. If there were a yeast category for the Methuselah Foundation's Mprize (an award given to scientists who significantly increase the lifespan of mice), Dr. Longo would have won handily. In both yeast and mice, a surefire way to enhance longevity is through caloric restriction (CR), which is essentially a state of persistent hunger. On its own, CR can produce a 3-fold and 30-50% lifespan increase in yeast and mice, respectively. ... Dr. Longo has helped identify the downstream molecular targets of CR, so with appropriate drugs and genetic manipulation, food abstinence may not be necessary."

Link: http://singularityhub.com/2010/12/22/innovation-and-outreach-at-the-worlds-oldest-school-of-gerontology/

Lipofuscin is a mix of metabolic byproducts that the body cannot break down. It accumulates with age, and causes some important forms of cellular dysfunction that contribute to aging. Ideally researchers would be working on ways to periodically clear liposfuscin from the body, but here they are investigating how it might be made less damaging: "Lipofuscin, a highly oxidized aggregate consists of covalently cross-linked proteins, lipids and sugar-residues, and is one of the major lifespan-limiting factors in postmitotic aging cells. An artificial model of this material, showing characteristics and effects comparable to the natural form, has turned out to be very useful for in vitro studies. Artificial lipofuscin was used to investigate its effects on the viability of human fibroblasts, its rate of uptake and its ability to inhibit the proteasomal system. The inhibition of the proteasomal system is one of the major aspects of the cytotoxic effects of lipofuscin. We present here that this proteasomal inhibition is due to a proteasomal binding on the lipofuscin surface motifs, degradable by protease K. Furthermore, removal of surface peptide structures by protease K strongly reduces cytotoxic effects of lipofuscin and binding of cellular proteins and proteasome to intracellular protein aggregates." Achieving this end would still leave the lipofuscin stuck in the cell, bloating the lysosomes, however - breaking it down would be much better.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21167934

The entertaining aspect of sparsely studied questions is that you'll find the evidence to be all over the map. No study can be considered in isolation, as many are in some way flawed - the right way to read science is to look at the flow and interaction of many groups and their research results. But if only a few researchers are publishing on a given topic, there's no real way to balance their work in a broader context. The only thing to do is wait.

We might look at blood type and longevity in this context, as a paper on this topic recently caught my eye. I don't recall reading anything on blood type and life expectancy in the past few years at least, so I know it's not a mainstream concern or a matter of common knowledge in the research community.

ABO Blood Type and Longevity

To assess the observation that blood type B might be a marker for longevity, we reviewed the records and determined the ABO blood types of all patients who died in our hospital in 2004. ... In our patient population, the percentage of patients with group B blood declines with age. The survival curve in group B was worse than that in groups A, O, and AB. These findings suggest that in our patient population, blood group B is not a marker for longevity but may be a marker for earlier death.

Which seemed interesting enough to merit a very brief search of the literature to see what else was written on the topic. That turned up this paper from 2004:

Blood type B might imply longevity

The aim of the present study was to investigate the association between blood groups and life expectancy. We compared frequencies of ABO blood group in 269 centenarians (persons over 100 years) living in Tokyo and those in regionally matched controls ... Our findings suggest that blood type B might be associated with exceptional longevity. Responsible mechanisms need to be investigated.

This is par for the course in biology. They might both be right, or they might both be wrong. Either way, both centenarian genetics and the biochemical details of the aging immune system are presently under investigation by a fair number of researchers. If there is a good answer to be discovered over the next decade or so as to whether - and how - blood type might influence longevity in various populations, it will probably come as a side-effect of these areas of research.

As is true of a range of the scientific research I reference here at Fight Aging!, that this is interesting doesn't mean it has any great relevance for the future of our longevity. Either SENS or SENS-like repair biotechnologies are developed over the next three to four decades, or we'll all grow old and die. Oh, we'll probably live slightly longer than our parents in that scenario, thanks to drugs that manipulate metabolism to slow the rate at which biological damage accumulates, but that would be a pretty poor outcome in comparison to real, working rejuvenation medicine to make people young for as long as they want.

One effect of developing biotechnology to repair the biochemical damage of aging is that the quirks of our biology will become irrelevant. No one will scrabble for a little statistical gain here or there, or worry about blood type, exercise, calorie restriction, their genes, or whether they have a good mitochondrial haplotype. It will be a great leveling of the hand dealt to us at birth, as well as eliminating the suffering and frailty of of aging.

So interesting research is interesting, especially when it illuminates truths about the way in which the research process proceeds in sparsely populated reaches of the life sciences - but don't mistake that for relevance.

As you might know, the naked mole rat is of great interest to aging researchers: "For three decades, Old Man selflessly helped scientists unravel the mysteries behind Alzheimer's, osteoporosis, cancer and other age-related diseases. Born in Kenya, he lived an active life - including siring offspring - until early Thanksgiving, when his body was discovered in a lab at the Barshop Institute for Longevity and Aging Studies on the campus of the Texas Research Park. A naked mole rat, Old Man was believed to be 32. ... The Barshop Institute m[aintains] the world's largest mole rat colony. About 2,000 of the tiny, burrowing rodents whose most distinctive feature is their sharp, protruding teeth, live and breed in four basement labs. With their long, hairless bodies and translucent pink skin, they look a bit like Vietnamese spring rolls with legs. ... Because these natives of East Africa live an average 26 years (compared to the 2- to 4-year lifespan of other rodents), they're well-suited for studies of age-related disease. For example, older mole rats develop the same type of brain plaque as that found in Alzheimer's patients. But for reasons unknown, they don't experience similar cognitive decline. Their bones also stay strong and healthy well into their later years. And perhaps most intriguing, mole rats very rarely develop cancer - a common cause of death among other rodents. In fact, when immune-suppressed mice were injected with naked mole rat cells containing tumor-forming genes, they didn't develop cancer. ... Among the many mole rats at the institute, however, Old Man stood out. Because of his advanced age and vigor, he'd claimed a special place in the hearts of many researchers. Laboratory animal attendant Cody Villanueva discovered his body early Thanksgiving morning. 'Oh, it was a sad day,' she recalled. 'I cried. We all did.'"

Link: http://www.mysanantonio.com/news/local_news/article/Old-Man-the-naked-mole-rat-is-no-more-913897.php

For some years now, researchers have been deciphering the mechanisms of regeneration in lower animals - limbs and organs regrown when lost. Here is an example of the sort of detail work taking place today: "Human regeneration is mainly limited to small portions of liver tissue, bone, or muscle, yet understanding how regeneration occurs in other taxonomic groups may enable scientists to improve human regenerative abilities in the future. ... Lizards can regenerate facial bones, certain areas of the spinal cord, and, as is most commonly known, most lizards can regenerate their tail - including muscles, cartilage, and spinal cord. The regenerated tail does not contain bone, but instead is supported by a tube of hyaline cartilage - the same cartilage humans have lining many of their joints. With widespread medical problems such as arthritis and spinal cord injuries, the application of these regenerative abilities is of extreme interest to medical institutions. .. Many vertebrate and invertebrate species can regenerate tissues, but there are several kinds of regeneration. Lizards most likely use stem-cell mediated regeneration, where new cells involved in regrowth arise from tissue-specific progenitor cells. This type of regeneration is the best bet for a regenerative process compatible with the human system ... the beauty is that now we know enough about development that we can actually have candidates for what cells are making this new tail - we can have guesses as to what might be right. ... Once we understand the nuts and bolts of how this is happening, we can use available technologies to manipulate and change that, then we will try to translate that to the mouse model."

Link: http://www.physorg.com/news/2010-12-tale-told-tails-gained-anoles.html

The title of this post was recently offered up as a pity quote on the Gerontology Research Group mailing list:

"Death is an inconvenient obstacle on the road to immortality."

The spirit in which this is intended is evidently that an army of biogerontologists and supporters should marshal, march, and trample death beneath their sandaled feet - to leave it broken in the dust upon the road that leads to rejuvenation biotechnology and agelessness.

That trampling will undoubtedly happen, albeit far from soon enough. If you stop to think about this for a moment, however, you might conclude that the defeat of death should not in fact be the conceptual focus of efforts to extend the healthy human life span. Let's try an analogy here:

The ground is an inconvenient obstacle on the road to flight.

Fail at flying, and a harsh encounter with the ground is your fate - in much the same way as death by aging is the fate that awaits us should we fail to achieve the technologies capable of repairing the biological damage of aging. Yet heavier than air flight wasn't achieved though a focus on the ground: the early aeronauts and their supporters didn't raise funding and convince the public of the viability of heavier than air flight through "defeat the ground!" campaigns. Their eyes looked up, to the skies, to rapid travel across land and ocean, to daring acts and barnstorming.

Returning to physical immortality - meaning the state of agelessness attained through biotechnology and diligent repair - then we might see that the grail here is life achieved, not death denied (or trampled). It is living, being healthy, able to plan ahead for decades without fear, to not be faced with inevitable pain, suffering, and frailty. These points are the focus.

Researchers run short-term studies on calorie restriction because it's cheaper and faster than long-term studies. Fortunately some of the biological changes brought on by calorie restriction take place fairly rapidly, so this is still a way to learn something. Here is one of the results: "Recent evidence supports the contention that cellular senescence is associated with, and may even be a cause of age-related functional impairment. Senescent cells accumulate in multiple tissues with advancing age. Cellular senescence causes a variety of cell types to acquire a pro-inflammatory secretory phenotype that produce a variety of cytokines, chemokines, and extracellular matrix remodeling proteases that are associated with tissue destruction. Chronic presence of senescent cells can accelerate cancer progression, possibly because of this inflammatory secretory phenotype. Engineered deposition of senescent cells in a single organ, skin, can cause functional impairments in multiple organs similar to those occurring with aging. Finally, senescent cell accumulation in progeroid animal models is associated with dysfunction resembling that of aging. Caloric restriction attenuates processes that have been implicated in cellular senescence, including generation of reactive oxygen species (ROS), growth hormone/insulin-like growth factor-1 signaling, and inflammation. Does caloric restriction in fact reduce cellular senescence? [An] important study [found] short term dietary restriction in middle-aged mice is associated with decreased abundance of senescent cells in the liver (centrilobular hepatocytes) and intestine (crypt enterocytes)."

Link: http://www.impactaging.com/papers/v2/n12/full/100247.html

Recent research into the causes of Alzheimer's disease: "Do rising brain levels of a plaque-forming substance mean patients are making more of it or that they can no longer clear it from their brains as effectively? ... Clearance is impaired in Alzheimer's disease. We compared a group of 12 patients with early Alzheimer's disease to 12 age-matched and cognitively normal subjects. Both groups produced amyloid-beta (a-beta) at the same average rate, but there's an average drop of about 30 percent in the clearance rates of the group with Alzheimer's. ... Scientists calculate this week [that] it would take 10 years for this decrease in clearance to cause a build-up of a-beta equal to those seen in the brains of Alzheimer's patients. The results have important implications for both diagnosis and treatment. ... Scientists are now interested in learning how a-beta, a byproduct of normal metabolism, is moved out of the brain for breakdown and disposal. As these details come in, they will be essential for physicians working to diagnose the disease before symptoms develop and for drug developers, who can target the problems with pharmaceuticals. A-beta was recognized long ago as a key component of the brain plaques found during autopsies of Alzheimer's patients. One of the ways the brain clears away the a-beta normally produced by brain cell activity is by moving it to the spinal fluid for disposal. Studies have suggested that a drop in spinal fluid levels of a-beta may be a presymptomatic indicator of Alzheimer's disease, possibly because a-beta is getting stuck in the brain and starting to accumulate there." You might also look back at research into the functional decline of the choroid plexus in connection with Alzheimer's: it is a biological filtration system, and its progressive failure may be the cause of lower rates of clearance.

Link: http://www.eurekalert.org/pub_releases/2010-12/wuso-apc120710.php

Cryonics, as you no doubt know by now, is the low-temperature storage of the recently deceased. The fine structure of the brain can be very well preserved - well enough that all the data that forms your self remains intact. Future medical technologies, such as applications of molecular nanotechnology, will eventually prove capable of repairing cryopreserved individuals and restoring them to life. A number of people have been cryopreserved and stored over the past few decades, and a modest community of cryobiology researchers, workers, advocates, and funding sources continues this work:

Death is not a topic that people like to think about, and that is just as true of healthy life extension advocates as anyone else. We have to recognise, however, that the future of healthy life extension (regenerative medicine, stem cell therapies, understanding the biochemical processes of aging, and nanomedicine, to name a few fields) will not arrive soon enough to benefit everyone. Many people are too old, or suffer from other conditions that will kill them before cures can be developed. This is an unpleasant reality that we must face.

Do we just write these people off and forge ahead regardless? Of course not. Instead, we turn to the science and business of cryonics, a serious effort to solve this problem that has been underway since the early 1970s.

My attention was recently directed to a series of presentations by Mike Darwin, which are in part an analysis of the failure of the cryonics community of past decades to blossom into a large industry, and in part a personal recollection of that history. If you want to understand more about the history of the cryonics movement, and how it came to be where it is today, you should certainly read this:

These are the URLs for the completed portions of the lectures entitled: Cryonics: An Historical Failure Analysis. Four parts are completed, two have been fully edited and proofed. The second series of lectures on how to redress the problems discussed in the first lectures will be a limited distribution.

Part I
Part II
Part III

Please note that Part III is still in draft form and I am currently in discussion with the editor about a number of issues. It is possible, and even likely, that there will be significant modifications in the near future.

...

Before I begin the formal, structured part of this presentation, a few words are in order to put it into context. We live in an age where passion and strong emotion have been largely removed from daily discourse and are now considered acceptable only in the realm of fiction; in movies and video games. Characters there are free to speak in extremes and to speak passionately; not so those of us who inhabit the real world. I will be breaking that taboo today because what I am going to talk about is a life or death issue for you, for me, and for the 7 billion or so other human beings on this planet. My life matters to me a great deal, and I'm not ashamed to admit it.

The failure of cryonics to join the ranks of other medical technologies in generating a growth market and worldwide provision of services is a communal failure for all of humanity. Over the decades since cryonics was first seriously proposed and low temperature storage of human tissue became technically viable, perhaps two billion people have died, every one of them an individual of worth, perspective, and unique experience. Every death is a tragedy, and yet deaths occur by the tens of thousands every day, an endless river of horror, pain, and suffering - and in the end, the destruction of oblivion.

This state of nature did not need to continue; cryonics could have spread and succeeded, or plastination in its stead, and many of those lost lives could have been saved. Their bodies and brains, the fine structure and data of memories left intact, would even now be stored, awaiting future technology that could return them to life once more.

Those lost lives are upon our hands and the hands of our parents and grandparents. Saving them was the path not taken.

From Daybreak Magazine: "I think immortality is in the same class as Utopia, infinity and perfection: a great destination to travel to, but one that can never be reached. Yet we should try, nevertheless. While immortality is an unreachable ideal, the effort of reaching it will bring huge progress and immense advantages. So let's be a tad more realistic and call it the quest for longevity, or extreme longevity. Problem is, a lot of people think we shouldn't be on this quest anyway, because of several misconceptions. ... Will McIntosh said (I'm paraphrasing here): "the human psyche is not wired for immortality: in almost every thing we do lies the shadow of our oncoming demise." However, this assumes that humans will not change. I think humans will change. Actually, humans are already changing, and have been changing throughout history. ... it will take time to develop much longer lifespans, followed by extreme longevity. Time enough for humans to change, and to adapt successfully to a much longer life. People have been changing all the time - albeit at a much higher rate in the past 100 years - and have been able to cope. Why shouldn't we be able to do so in the future? ... such thinking - [that] humans will remain the same while the world around them changes - is 'a failure of the imagination'. I agree: by the time extreme longevity is possible, we will have developed the right mindset for it."

Link: http://daybreakmagazine.wordpress.com/2010/12/18/intimations-of-immortality-are-we-ready-for-extreme-longevity-or-do-we-even-deserve-it/

From Common Sense Atheism: "Let's imagine that every human who had ever lived awoke in the morning with a terrible migraine just behind the eyes for one hour. Nobody could do any work during this time. We just had to endure for one hour, and when it dissipated, go about our business, and dread the next day's migraine. There was no cure for the morning migraine, and none in sight. It was, unfortunately, fixed into the very nature of being human. I have no doubt we would soon begin to rationalize these morning migraines. We would tell ourselves that they make the rest of each day more wonderful by contrast, and that we would not properly appreciate the rest of each day were it not for the migraines. Someone might even venture to say that it's the morning migraines which makes the rest of life meaningful. But now imagine that thousands of years pass, and very advanced scientists discover that morning migraines can be cured - with methods inconceivable to previous generations. Post-migraine generations look back on past generations and wonder: 'How could they tolerate those awful morning migraines? What a horrible way to live, every day! Thank goodness we found a cure!' I want to say the same about death. We rationalize death because we don't think it can be avoided. But death is horrible, like cancer. Death thwarts an awful lot of desires. I don't think much about death, and I don't worry much about it, but I'm sure that when I lie on my deathbed I will have lots more I wanted to do with my life, and not being able to do those things will suck. But here's the good news. Death can be solved."

Link: http://commonsenseatheism.com/?p=12888

Aging science blog Ouroboros recently roused from its slumber for an excellent series of posts covering the Bay Area Aging Meeting held earlier this month. This is a well attended gathering of biogerontologists, who are fairly numerous in that part of the world. There are a number of important laboratories in California, such as the Kenyon Lab at UCSF and the Buck Institute for Age Research, which leads to a fair turnout at most local life science events.

Here is the coverage by session, one post for each set of presentations, with some of the highlights singled out and quoted below:

Bay Area Aging Meeting: Session I

Cognitive decline occurs with age: speed of processing, working memory, and long-term memory all decline. Presumably cell loss is partially to blame - not only loss of neurons, but also other types of cells (e.g., oligodendrocytes). Neural stem cells (NSC) can regenerate lost cells to some extent, but their ability to do so diminishes with age.

The Brunet lab is looking at the idea that pathways that control lifespan in "lower" organisms (worms; yeast) may be involved in regenerative capacity in "higher" organisms (us; mice). Rafalski's work is focusing on the now-famous SIRT1. SIRT1 is downregulated over the course of differentiation, so there's a smoking gun - but is there a causative relationship between SIRT1 downregulation and loss of regenerative capacity in NSCs?

Bay Area Aging Meeting: Session II

Furman looked at the response of 85 individual human subjects to vaccination, making a wide range of measurements (antibody titer, cytokine levels, gene expression), with the goal of creating a classifier system that can be used to predict the efficacy of the immune response. Young people tend to respond to antigens very similarly to one another (i.e., efficiently), whereas elderly subjects were split into two categories: cytokine responders and non-responders. These categories correlated with expression of genes associated with longevity, suggesting that immunosenescence and longevity represent two sides of the same coin.

Bay Area Aging Meeting: Session III

Regulatory T cells (Treg) maintain immune tolerance, i.e., they stop the rest of the immune system from attacking the body. They accomplish this by suppressing differentiation of naive cells and the activation of effector cells. This, in turn, helps to prevent autoimmune disease and graft rejection. However, Treg cells increase their activity during aging, which might make elderly people more susceptible to infection.

Treg activity is regulated by FoxP3, which is in turn modified by acetylation that is regulated by SIRT1. ... In questions, I asked whether SIRT1 inhibition could therefore be used to prevent autoimmune disease - the short answer is "yes"

Bay Area Aging Meeting: Session IV

If aging is an engineering problem, then we should be able to solve the engineering challenges more easily in simple systems. By introducing genes from a long-lived organism into the genome of a short-lived organism, it should be possible to add pro-longevity functions - in effect "upgrading" the short-lived animal so that it lives longer. Sagi has set out to do just that, by transferring genes from the long-lived zebrafish (4-year lifespan) to the short-lived worm (4-week lifespan).

...

The next obvious question: Can "upgrade" genes be combined to further increase lifespan? Indeed they can: several pairwise combinations of genes combined to extend lifespan longer than either single gene alone. At some point it worked a little too well: the lifespan of the worms started getting long enough that the survival curves became unwieldy.

Evolution doesn't select for longevity - a fact amply demonstrated by how many different minor changes in metabolism can make worms, flies, and mice live longer in good health.

Fifteen years ago, this paper or one with similar sentiments wouldn't have been accepted for publication - or if it had, it would have achieved nothing but harming the funding prospects of its author. The aging research community has only recently emerged from an era of self-censorship on the topic of engineering greater human longevity, and a field whose members do not talk about achieving a given goal will certainly make no progress towards that goal. From the abstract: "Although we do not know everything about aging, we now know enough to start its pharmacologic suppression using clinically approved drugs. Aging turns out to be driven by sensing-signaling pathways (such as the mTOR pathway). Given that some inhibitors of the mTOR pathway are already in clinical use, there is a unique opportunity to suppress aging, while treating and preventing diseases. By itself this will answer some burning questions in gerontology. Here I discuss a proposal, starting from retrospective clinical studies to animal and cellular models to drug screens in order to develop non-toxic and effective schedules and drug combinations for extending healthy life span in our lifetime." This is representative of the more eager members of the mainstream of biogerontology, focused on slowing aging through metabolic manipulation.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21150328

From Maria Konovalenko: "Melanie Swan, MBA, is an Affiliate Scholar of the IEET [and] recently summarized some important themes in aging research that were discussed at the second Bay Area Aging Meeting. ... Two interesting talks concerned UCP2 (mitochondrial uncoupling protein 2) an enzyme which reduces the rate of ATP synthesis and regulates bioenergy balance. UCP2 and UCP3 have an important but not yet fully understood role in regulating ROS (reactive oxygen species) and overall metabolic function, possibly by allowing protons to enter the mitochondria without oxidative phosphorylation. The mechanism was explored in results that worm lifespan was extended by inserting zebrafish UCP2 genes (not natively present in the worm) ... Two talks addressed the issue of immune system compromise. One team created a predictive analysis that could be used to assess an individual's immune profile and potential response to vaccines by evaluating demographics, chronic infection status, gene expression data, cytokine levels, and cell subset function. Other work looked into the specific mechanisms that may degrade immune systems in older organisms. ... Aging and other biological processes become more complicated with progression up the chain of model organisms. What works in yeast and worms may not work in mice, and what works in mice and rats may not work in humans. Some interesting research looked at ribosomal proteins, whose deletion is known to extend lifespan in model organisms. The key points were [that] there was fairly little (perhaps less than 20%) overlap in lifespan-extending ribosomal protein deletions conserved between yeast and worms."

Link: http://mariakonovalenko.wordpress.com/2010/12/16/melanie-swan-a-summary-of-important-themes-in-aging-research/

The SENS Foundation, freshly infused with money from a recent half-million dollar donation, is hiring a new research assistant for their California research center. As you'll all know by now, the Foundation works on developing rejuvenation biotechnologies to repair and reverse the damage of aging. Do you want to be a part of that grand and noble effort? Then read on.

SENS Foundation seeking to hire Research Assistant

SENS Foundation is hiring a Research Assistant for our research center located in Mountain View, CA. Qualified candidates will a BS or MS in the chemical/biological sciences and two years of work experience. Experience should be in using standard equipment, including but not limited to standard bench cell biology/biochem/molecular biology techniques. Good fundamental laboratory skills to include safety, excellent pipetting skill, and mammalian cell culture.

Duties will include cell culture, transfection, microscopy, and protein work (western blot, IP, etc.). Subcloning / PCR cloning a plus. Experience working with mitochondria a strong plus. Research assistants will work under the supervision of the facility's senior researcher to carry out experiments directed towards establishing the viability of the SENS mission and chosen therapeutic goals. Research Assistants will receive general instruction on routine work and detailed instruction on new assignments. Other duties include providing support in areas such as lab maintenance, maintaining lab notes, procuring supplies, organizing research materials, and editing and filing documentation.

They are looking for mitochondrial research experience because the MitoSENS project is forging ahead. The goal of this line of work is to duplicate vulnerable mitochondrial genes in the cell nucleus, while enabling the vital proteins they produce to make their way back to the mitochondria. Thus even if the genes become damaged in the mitochondria, there will be a backup source of proteins to avoid the normal consequences of mitochondrial DNA damage.

For over 30 years mutations in mitochondrial DNA have been suspected to be important contributors to aging. If we can incorporate working copies of that mtDNA into our nuclear DNA, the mtDNA will be rendered superfluous and any mutations it suffers will be inconsequential.

Do you have laboratory experience? Then apply. After all, there is no more important task than helping to eliminate degenerative aging and age-related disease. No other area of present human endeavor has the potential to save as many lives and relieve as much suffering.

From the Methuselah Foundation Blog, a message from founder and CEO Dave Gobel: "It has been a while since I sent you an update and there is plenty of good news to share as we work together towards longevity. I also want your input as we make plans for the coming year. ... Methuselah Foundation has successfully promoted the extension of healthy human life - the science of aging has gained acceptance and broad-based support thanks to your ongoing contributions. Now we are strongly supporting science that will lead to tissue engineering and organ regeneration. We will be the catalyst to speed up the development of organ replacement. ... I am continually delving into every area of science, the work being done in universities, labs and biotech companies, to see the latest research and how it might contribute to longer life. I am convinced that there are many viable solutions but we, uniquely, are in a position to move them to a practical place. With this mission in mind we created the NewOrgan Prize. Based on our success with the Mprize, we anticipate this new prize will accelerate the rate of research and bring us closer to practical solutions. ... We must continue to accelerate practical scientific solutions related to aging. You and I - not just our children and grandchildren - should benefit from the advances in tissue engineering that are already on the table. This is why I need your input. We are contemplating a number of initiatives in support of this drive but we want to have the greatest possible impact. I would appreciate your thoughts and suggestions. Please continue reading and I believe you will have a clear understanding of the potential and, hopefully, will have some thoughts to share." Head on over to read the rest of the post: if you have opinions and good ideas, send them to the Foundation."

Link: http://blog.methuselahfoundation.org/2010/12/id_like_your_opinion_as_we_plan_for_the_future.html

I'd neglected to mention that the Methuselah Foundation newsletter for November was posted a couple of weeks ago: "A year ago Methuselah Foundation presented a special Mprize Lifespan Achievement Award to Z. Dave Sharp for his work with rapamycin. By the end of the year Science, Nature and TIME magazines each featured rapamycin - an antibiotic used in transplant patients that extended the life span of aged mice - as one of the most significant and exciting scientific breakthroughs of 2009. At our 2009 presentation at the Friar's Club in New York City, Dave told us a funny (after the fact) story about how the experiment ended up being done on old mice. Basically, by the time they figured out how to sneak the rapamycin into the mice food, the mice had gotten old. But three labs were on stand-by, set to start so they proceeded - making the results all the more remarkable. Rapamycin reversed aging! Now Dave has informed us that a second entire replication of the life span study has been repeated with the same results. This time the mice started taking rapamycin at nine months of age. That makes a total of SIX independent replications of the experiment!" The newsletter also provides updates on several of the Foundation's present projects and investments, such as organ printing startup Organovo.

Link: http://blog.methuselahfoundation.org/2010/11/methuselah_foundation_newsletter_november_2010.html

When nematode worms were first engineered to live significantly longer in good health, not very many years ago, it was a big deal. Today, few people beyond the life science community take much notice of each new study to result in a way to extend life in lower animals. Today I briefly scanned through the latest aging research papers referenced by PubMed and saw three separate reports of aging slowed in nematodes and flies, all published in just the past week or so.

So the world turns: the remarkable becomes unremarkable. This is where we'd like to be with human engineered longevity - for it to be an unexciting topic, well-studied, with the work of commercial development well underway, and everyone taking it for granted that healthy lifespan will be made much longer through medical science. We're not there yet, evidently.

But back to those papers, representative of the breadth of metabolic investigation and experimentation presently underway. Researchers are trying genetic alterations, drugs, and a variety of other means to change aspects of metabolism shared between worms, flies, mice, and humans. They are in search of a longer-lasting and more resilient configuration of life, one which could be brough to humans via drugs or genetic engineering. This is an ambitious undertaking, far more so than simply trying to repair the metabolism we have - but yet it will have less useful results in the end. It's a strange world we live in.

Increase of Drosophila melanogaster lifespan due to D-GADD45 overexpression in the nervous system

The GADD45 protein family plays an important role in stress signaling and participates in the integration of cellular response to environmental and physiological factors. GADD45 proteins are involved in cell cycle control, DNA repair, apoptosis, cell survival and aging, and inflammatory response by complicated protein-protein interactions. ... Our data show that overexpression of the D-GADD45 gene in the nervous system leads to a significantly increase of Drosophila lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females, which agrees with the sex-dependent expression of this gene.

A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans

An unequivocal demonstration that mitochondria are important for lifespan comes from studies with the nematode Caenorhabditis elegans. Mutations in mitochondrial proteins [lead] to a dramatic increase in the lifespan of this organism. One theory proposes that toxicity of mitochondrial reactive oxygen species (ROS) is the cause of aging and predicts that the generation of the ROS superoxide should be low in these mutants.

Here we have measured superoxide generation in these mutants and found that it is in fact elevated, rather than reduced. Furthermore, we found that this elevation is necessary and sufficient for longevity, as it is abolished by antioxidants and induced by mild treatment with oxidants. This suggests that superoxide can act as a signal triggering cellular changes that attenuate the effects of aging. This idea suggests a new model for the well-documented correlation between ROS and the aged phenotype. We propose that a gradual increase of molecular damage during aging triggers a concurrent, gradually intensifying, protective superoxide response.

The effect of dichloroacetate on health- and lifespan in C. elegans

Aging is associated with increased vulnerability to chronic, degenerative diseases and death. Strategies for promoting healthspan without necessarily affecting lifespan or aging rate have gained much interest. The mitochondrial free radical theory of aging suggests that mitochondria and, in particular, age-dependent mitochondrial decline play a central role in aging, making compounds that affect mitochondrial function a possible strategy for the modulation of healthspan and possibly the aging rate.

Here we tested such a "metabolic tuning" approach in nematodes using the mitochondrial modulator dichloroacetate (DCA). We explored DCA as a proof-of-principle compound to alter mitochondrial parameters in wild-type animals and tested whether this approach is suitable for reducing reactive oxygen species (ROS) production and for improving organismal health- and lifespan.

Many of the conditions that occur with age might be considered exaggerated forms of "normal" aging - one aspect of damage that has raced ahead in that person for some reason. In Parkinson's disease, this damage takes the form of a decline in dopamine-secreting cells in the brain. That happens to all people to some degree, but Parkinson's sufferers have a much greater loss of these vital cells. Here researchers demonstrate that a treatment for Parkinson's produces benefits for the same symptoms seen to a lesser degree in "normal" aging: "We wished to determine whether L-DOPA, a common treatment for the motor deficits in Parkinson's disease, could also reverse the motor deficits that occur during aging. We assessed motor performance in young (2-3 months) and old (20-21 months) male C57BL/6 mice using the challenge beam and cylinder tests. Prior to testing, mice were treated with L-DOPA or vehicle. Following testing, striatal tissue was analyzed for phenotypic markers of dopamine neurons: dopamine, dopamine transporter, and tyrosine hydroxylase. Although the dopaminergic markers were unchanged with age or L-DOPA treatment, L-DOPA reversed the motor deficits in the old animals such that their motor coordination was that of a young mice. These findings suggest that some of the locomotor deficits that accompany normal aging are responsive to L-DOPA treatment and may be due to subtle alterations in dopaminergic signaling."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21111775

More intelligent people live longer - and we could propose all sorts of mundane and obvious reasons as to why this is the case, such as a greater and more effective use of health knowledge and medical resources. Here, a researcher proposes that there is in fact a biological reason as well: "Intelligent people live longer - the correlation is as strong as that between smoking and premature death. But the reason is not fully understood. Beyond simply making wiser choices in life, these people also may have biology working in their favor. Now research in honeybees offers evidence that learning ability is indeed linked with a general capacity to withstand one of the rigors of aging - namely, oxidative stress. Ian Deary, a psychologist at the University of Edinburgh, has proposed the term 'system integrity' for the possible biological link between intelligence and long life: in his conception, a well-wired system not only performs better on mental tests but is less susceptible to environmental onslaughts. Gro Amdam of Arizona State University and the Norwegian University of Life Sciences was intrigued by the idea and last year devised a way to test it in bees. ... Amdam hypothesizes that the ability to handle stress could be a component of system integrity; better overall stress resilience may contribute to both higher IQ scores and longer life. And if scientists can unravel what underlies these biological differences, they might be able to alleviate inborn disparities."

Link: http://www.scientificamerican.com/article.cfm?id=old-and-wise

We stand in the early years of a rapid, sweeping revolution in biotechnology. Every few months we see researchers demonstrate an entirely new capability, never before seen: controlling cells; spurring healing where the body would not heal on its own; building the basic elements of organs from scratch; depopulating donor organs and repopulating them with the patient's own cells - and more. As the cost of tools and knowledge in the life sciences continues to plummet, the pace of development accelerates. This rapid progress in applied biotechnology is the true grail of the computer age, enabled by cheap processing power and all the associated technologies that come with it.

Not so far down the road are organs grown to match our needs, stem cell transplants that heal our age-damaged tissues from within, artificial cells and engineered bacteria that scour our bodies for the waste products of metabolism that build up to harmful levels in the old. Beyond that even more impressive medical advances await: artificial immune systems, far better than the real thing, the complete implementation of the SENS program for rejuvenation medicine, and the dawn of the age of molecular manufacturing - everything you might need, from drugs to bioimplants, built atom by atom in desktop nanoforge machines.

Which brings us to an important point, buried in an otherwise unrelated post:

The utility of money is going to rise with advances in biotechnology. Some extra tens or hundreds of thousands of dollars set aside for medical expenses might save your life.

Whatever resources you have saved up today are growing more and more valuable with time - far more than their present market value would imply - because we are entering the age in which you can use saved resources to buy additional healthy life. With each passing year the amount of additional healthy life you could purchase increases. While that yearly increase is comparatively gentle now, and the amount of extra life very modest, both will become much, much larger ten years or twenty years from now.

So save. Save aggressively, and invest wisely in speeding the right biotechnology. One day that saved money will buy you access to medical technologies that provide additional decades of healthy life; that additional time and vigor added to your life span is far more valuable than whatever ephemeral trinkets you could choose to buy today.

Another set of potential human longevity genes, this time associated with immune system function, and from a Russian study: "The research was aimed at studying molecular genetics basis of human longevity. The genotyping of polymorphisms in genes of interleukins 6, 10, 12, and tumor necrosis factor-alpha from ethnically homogeneous population (Tatars from Bashkortostan Republic) has been carried out. Distributions of allele and genotypes frequencies in different age groups including old men and long-livers have been characterized. Associations have been revealed between age and -627C>A polymorphism of IL-10 gene in men, -572G>C polymorphism of IL-6 gene and -308G>A polymorphism of TNF-alpha gene in women. As a whole the data obtained by us confirm the assumption that polymorphism of cytokine genes can influence on human lifespan." All of these items are associated with the correct functioning of the immune system, and are already targets for drug development in the treatment of autoimmune disorders such rheumatoid arthritis, in which the immune system has become disarrayed and malfunctioning. We should expect to see statistically significant associations between human longevity and gene variants that improve the function and resilience of the most important bodily systems.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21137202

News of research with potentially broad application, given the degree to which immune system damage contributes to age-related frailty: researchers "have discovered that the human body can create its own vaccine, which boosts the immune system and helps prevent chronic inflammatory diseases. ... When administered in the form of a therapeutic vaccine it is able to effectively prevent and treat a number of different inflammatory disease models for multiple sclerosis (MS), rheumatoid arthritis (RA), skin hypersensitivity and allergic asthma (AA). ... The implications of the findings are large as they shed light on an important way that the body combats inflammation and autoimmunity. Moreover, they establish a therapeutic approach for using the newly discovered protein as a treatment for multiple conditions. ... Many inflammatory and autoimmune diseases are chronic and affect a large majority of people. Moreover, there is an inflammatory component to many common diseases, such as Alzheimer's, Parkinson's, RA, AA, MS, type II diabetes and cancers. The vaccine discovered by the researchers boosts special cells of the immune system, called NKT cells. ... NKT cells are a type of T cell that exert profound and diverse regulatory effects in disease, from autoimmunity to responses to pathogens and cancer. For over two decades since their discovery NKT cells have traditionally been considered to be activated by lipid antigens presented by CD1 molecules. However, Professor Issazadeh-Navikas' group was able to show for the first time the ability of a self peptide to activate NKT cells to suppress many tissue-specific inflammatory conditions including experimental autoimmune diseases."

Link: http://news.ku.dk/all_news/2010/2010.12/vaccineboostsyourimmunesystem/

A wealth of long-lived mammals can be found in the laboratories of aging researchers. The healthy life spans of these animals are extended by comparatively minor genetic alterations, drugs such as rapamycin, or environmental changes like calorie restriction that are used to identify targets for future genetic engineering. This is the domain of the metabolic engineers, who see no better way forward than to gently slow aging by tweaking the operation of human metabolism. It will be a long and expensive road, and at the end will not produce results that can help people who are already old. Metabolic engineering cannot produce rejuvenation, the reversal of aging - yet it is the dominant body of longevity science in this day and age.

Thus most of the new research you'll see or read about is directly only towards either understanding or at best slowing aging, with significant results not really expected for a couple of decades. Here is a review of the sort of foundational work taking place in this field:

Studies of the effects of single-gene mutations on longevity in Caenorhabditis elegans, Drosophila melanogaster and Mus musculus identified homologous, highly conserved signalling pathways that influence ageing. In each of these very distantly related species, single mutations which lead-directly or indirectly-to reduced insulin, insulin-like growth factor (IGF) or insulin/IGF-like signalling (IIS) can produce significant increases in both average and maximal lifespan. In mice, most of the life-extending mutations described to date reduce somatotropic (growth hormone (GH) and IGF-1) signalling.

The reported extensions of longevity are most robust in GH-deficient and GH-resistant mice, while suppression of somatotropic signalling 'downstream' of the GH receptor produces effects that are generally smaller and often limited to female animals. This could be due to GH influencing ageing by both IGF-1-mediated and IGF-1-independent mechanisms.

In mutants that have been examined in some detail, increased longevity is associated with various indices of delayed ageing and extended 'healthspan'. The mechanisms that probably underlie the extension of both lifespan and healthspan of these animals include increased stress resistance, improved antioxidant defences, alterations in insulin signalling (e.g. hypoinsulinaemia combined with improved insulin sensitivity in some mutants and insulin resistance in others), a shift from pro- to anti-inflammatory profile of circulating adipokines, reduced mammalian target of rapamycin-mediated translation and altered mitochondrial function including greater utilization of lipids when compared with carbohydrates.

None of this is useless knowledge: the more that is known about aging and biology in mammals, the easier it will be to strike off and build working rejuvenation technology that can repair and revert the biochemical differences between a young person and an old person. But we are already well past the point at which it is practical to do this: time spent acquiring further knowledge of aging biology is now nowhere near as valuable as time spent on building the known forms of repair-based rejuvenation biotechnology. The different in time taken to produce results and the difference between slowing aging and reversing aging is counted in hundreds of millions of lives.

While you were reading this sentence, a dozen people just died, worldwide. There. Another dozen people have perished.

And this will continue until we build the means to treat aging as a disease and cure the old by repairing the accumulated cellular and biochemical damage that is killing them.

More progress from the tissue engineers: "For the first time, scientists have created functioning human intestinal tissue in the laboratory from pluripotent stem cells. ... their findings will open the door to unprecedented studies of human intestinal development, function and disease. The process is also a significant step toward generating intestinal tissue for transplantation, researchers say. ... This is the first study to demonstrate that human pluripotent stem cells in a petri dish can be instructed to efficiently form human tissue with three-dimensional architecture and cellular composition remarkably similar to intestinal tissue. The hope is that our ability to turn stem cells into intestinal tissue will eventually be therapeutically beneficial for people with diseases such as necrotizing enterocolitis, inflammatory bowel disease and short bowel syndromes. ... To turn pluripotent stem cells into intestinal tissue, scientists performed a timed series of cell manipulations using chemicals and proteins called growth factors to mimic embryonic intestinal development in the laboratory. The first step turned pluripotent stem cells into an embryonic cell type called definitive endoderm, which gives rise to the lining of the esophagus, stomach and intestines as well as the lungs, pancreas and liver. Next, endoderm cells were instructed to become one those organ cell types, specifically embryonic intestinal cells called a 'hindgut progenitors'. The researchers then subjected the cells to what they describe as a 'pro-intestinal' cell culture system that promoted intestinal growth. Within 28 days, these steps resulted in the formation of three-dimensional tissue resembling fetal intestine that contained all the major intestinal cell types - including enterocytes, goblet, Paneth and enteroendocrine cells. The tissue continued to mature and acquire both the absorptive and secretory functionality of normal human intestinal tissues and also formed intestine-specific stem cells."

Link: http://www.eurekalert.org/pub_releases/2010-12/cchm-sct120910.php

Here is an example from Discovery News of one way in which popular science articles fall down: by focusing too closely on the research immediately to hand and failing to present the wider context. This article looks at the effect of damaging free radicals on life span in laboratory animals, but fails to talk in any detail about the range of research on hormesis effects: "Conventional wisdom has held for decades that free radicals cause aging, and that antioxidants, which squelch the reactivity of these highly reactive molecules, are a way to slow the process. But new work adds to a growing body of research that suggests the story is not so simple. In the new study published in PLoS Biology, worms that made more free radicals or that were treated with a free-radical-producing herbicide actually lived longer than normal worms. What's more, when the longer-lived mutant worms were given antioxidants, the effects were reversed, and the worms had a conventional worm lifespan. The finding flies in the face of the idea that antioxidants battle the effects of aging. ... what is emerging from this and other experiments is a view of free radicals - or, more precisely, reactive oxygen species - as a normal part of the body's stress response, with beneficial effects at certain levels."

Link: http://news.discovery.com/human/aging-free-radicals-antioxidants.html

If Fight Aging! seems slow, or has been down at times over the past few days, it is because the site is under a distributed denial of service attack. This appears to be at least partially due to automated comment spam scripts from a wide range of Asian locations, starting at the end of last week and a very large step up from the level of comment spam that Fight Aging! usually receives. It is possible that a foolish spammer simply issued an unintended command, or messed up the configuration file for their rented botnet rather than there being any malicious intent involved - it is not in a spammer's interest to take down the sites they are trying to infect with spam messages. While I would be delighted to see that longevity science and the future of human aging had become a contentious and high profile area of discussion, to the point at which partisans start attacking websites and other technical infrastructure, I don't think we're there yet. I am doing what I can to mitigate the ongoing attacks: over the past few days Fight Aging! has been moved to a new host, its software upgraded, and the whole system otherwise buffed. This was all accomplished in a comparatively short period of time, so please let me know if you see anything that is newly broken or otherwise gone awry.

Via in Search of Enlightenment I notice that the sole open access treat buried in the latest edition of Rejuvenation Research is a paper on the future of aging research. Along the way it also examines presently widely held beliefs that are at odds with the reality of scientific progress - to the point of holding things back, in fact.

[This paper] makes the case for reviving the Aristotelian conception of political science (namely, that it is the architectonic science). It also makes the case for prioritizing the imperative to tackle the inborn aging process and, most importantly, the obstacles that impede our ability to accurately perceive the importance of tackling aging.

Long time readers will know that I disagree with this author on a number of fundamental axioms regarding political organization and economics, but that doesn't stop it from being a well-constructed paper that is unambiguously in favor of engineering an end to aging. The future for a given field of scientific study tends to look rosier when people holding many different philosophies of life start supporting it, and especially when they have to fight against the mainstream of their community of thought in order to do that.

In any case, take a look and see what you think:

The greatest single threat to the health prospects of today's aging populations is the inborn aging process itself. However, many cognitive limitations and biases impair our ability to accurately perceive this reality.

...

if asked to simulate what a future with no cancer would be like, a person is likely to have a positive emotive response. The same would no doubt be true for eliminating any specific disease of aging, like Alzheimer disease, stroke, or diabetes. However, if asked to simulate what a future of slowed human aging would entail, our deliberations are likely to fall prey to some common prospection errors because of the complexities and indeterminacies of such a simulation exercise. Thus, biogerontologists often face what Richard Miller calls "gerontologiphobia" - "the irrational fear that ageing research is a public menace bound to produce a world filled with nonproductive, chronically disabled, unhappy senior citizens consuming more resources than they produce."

There's much more in that vein. Longevity science will not, of course, produce a world of eternally frail, age-damaged people. Firstly it doesn't actually seem possible to achieve that end, given what reliability theory tells us about the way in which complex systems respond to damage and repair, and secondly researchers and the people who fund their efforts are aiming to build technologies that can extend or restore youth. We want to be able live as though young for longer, or regain the youthful biology we lost - we'll choose to pay a premium for that over any other option, and scientists and their funding sources are just as much a part of the market economy as everyone else. They follow the money, as the flow of money is no more than choices, preferences, and wishes writ large and made evident.

From Newsweek: "Luke Masella was born with spina bifida, a birth defect that paralyzed his bladder. By the time he was 10 years old, despite various treatments, his kidneys were failing. Toxins were building up in his blood, and he had lost 25 percent of his body weight. That's when Luke and his parents opted for a radical solution - a brand new bladder. It might sound like science fiction, but growing new organs from scratch has already become reality. In addition to bladders, scientists have engineered new skin, bone, cartilage, corneas, windpipes, arteries, and urethras. Human organs fail for a multitude of reasons; genetic deformities, injuries, and disease can all damage them. Organ transplantation is an option, of course, but it's risky, and too often there aren't enough donated organs to meet the growing need. So 25 years ago, a group of scientists embarked on an audacious quest: the creation of whole new organs. Brothers Joseph and Charles Vacanti at Harvard Medical School and Robert Langer of the Massachusetts Institute of Technology first promoted the idea of 'tissue engineering' or 'regenerative medicine.' The scientists knew that every organ has a 'scaffolding' - a structure that gives it shape - and many different types of cells with different functions. There are millions of cells, all arranged in an exact order. ... After the scaffolding came the hard part, the part that caused most scientists outside the field to predict that growing new organs would fail. Even if you could build a scaffolding and procure the cells to drape onto that scaffolding, then what? Surely no scientist could assemble millions of cells, one by one and each in the right place, as if the organ were a giant jigsaw puzzle." But of course researchers have proven that they can do this, and the field is presently progressing very rapidly.

Link: http://www.newsweek.com/2010/12/07/future-of-medicine-growing-new-organs.html

From Mike Kope, SENS Foundation CEO: "Last night, Peter Thiel hosted 'Breakthrough Philanthropy', a dinner and presentation event showcasing eight non-profit organizations focused upon game-changing approaches to their fields. It was a wonderful opportunity for us to convey our message to a large group of entrepreneurs and philanthropists interested in the genuinely transformative. Our thanks to the Thiel Foundation, and the Seasteading Institute, for their efforts in creating that event. Here are my remarks from the presentation. ... We've gotten very good at conquering infectious diseases. None of you will suffer from polio, or smallpox, or, likely, measles or diptheria. But the truth is, we haven't extended that kind of success to the problems of aging. You will know someone suffering from cancer, from Alzheimer's, from Parkinson's disease. We haven't yet eradicated a single, major age-related disease. This is despite great advances in therapeutics, despite trillions in research underway around the globe, and despite the brightest minds working in an entire, thirty year long biotech revolution. Ten years ago, our CSO Aubrey de Grey first suggested … a slightly different revolution. His core idea was a damage repair model called SENS, and a recognition of a simple problem: when medical science focuses upon disease - when we wait for disease to develop - then what we learn is how to chase the pathology - and we haven't gotten very good at that. But if we look instead at the damage building up as a result of the normal metabolism of being alive, then we can learn to repair that damage before those deadly pathologies develop. That's it; that's all that SENS means: it's a model that steps away from the expensive and tangled 'pathology chase' and focuses instead upon identifying, addressing and removing the damage that is building up inside you; the damage that will eventually cause disease."

Link: http://www.sens.org/node/1858

Investor Peter Thiel recently held a gathering of the well off and motivated, encouraging them to invest more daringly in philanthropic projects. To take bigger risks and aim to change the world, rather than succumb to the curse of incrementalism - which is a road to accomplishing little of worth when all is said and done. What use is great wealth without the imagination and will to reach for the sky and shake the foundations?

So that said, I'm pleased to note that the SENS Foundation received a $500,000 donation as a result of Thiel's event - or more likely the result of the invisible toil of networking and discussion behind the scenes, and which has been building up to this for some time. Regardless of the mechanisms behind this sizable donation, it is very welcome development indeed. Congratulations are due to all concerned, and I hope that this will be one of many such large donations across the next decade of fundraising and research:

The global scientific community is increasingly recognizing the role of rejuvenation biotechnologies in addressing age-related disease. This week, Arizona-based businessman Jason Hope announced a $500,000 donation to SENS Foundation, a California-based non-profit organization that works to develop, promote and ensure widespread access to rejuvenation biotechnologies which comprehensively address age-related disease.

"I have had great interest in the SENS Foundation and Dr. Aubrey de Grey's work for some time now. I believe their work is essential to the advancement of human medicine and their approach to the overall problem of human aging and its associated diseases (Alzheimer's, Atherosclerosis, Diabetes, etc.) is the only way to go. Their work and the work of others that they support will drive the complete redefinition and reshaping of the healthcare, pharmaceutical, and biotech industries as we know them today. The advancement of rejuvenation biotechnologies is not only extremely important, but it is the future. I am honored to support the SENS Foundation in its efforts, and hope my support helps drive faster results for all of humanity," said Jason Hope.

Here's a selection of other coverage of the event:

We Will Be At the Billionaires' Singularity Dinner Tonight:

[This] is planned to be a fairly straight forward event. After an hour or so of networking there will be a few opening remarks from The Thiel Foundation, and Patri Friedman of the Seasteading Institute. After that, we'll be on to five minute “lightning talks” from organizations at the cutting-edge of technology. That list includes the SENS Foundation, Singularity University, Singularity Institute, Foresight Institute, Humanity+ (with Ben Goertzel), Santa Fe Institute, and Xprize Foundation (with Peter Diamandis). Each of these groups is looking to push the boundaries of science, politics, and/or society, and could provide disruptive (and hopefully positive) changes in the years ahead. After their talks, Thiel will give a few closing remarks and attendees will continue to mingle and connect until the event closes.

How Was the Billionaire’s Singularity Dinner? See For Yourself In These Videos

Talking to various people at the event, it surprised me how many attendees were already affiliated with at least one of the presenting groups. Even when someone hadn't previously donated to any of the organizations, they already knew something about their policies and interests. In other words, I'm not sure how much the lightning talks were really giving new information to their audience. Of course, educating people in the finer points of each institution likely wasn't the point. It was probably more about cross pollinating between the organizations. Apparently, that's how a lot of these fund raisers go. It will be interesting to see how successful the evening proves to be, and to find out whether or not The Thiel Foundation's matching offer entices people to donate.

Peter Thiel Challenges Silicon Valley’s Wealthy to Back "Breakthrough" Philanthropic Causes

Last night Silicon Valley icon Peter Thiel, of PayPal fame, gathered eight of his favorite future-oriented organizations and a couple hundred of his wealthiest friends in an auditorium at San Francisco's Palace of Fine Arts and made a magnanimous offer. For every dollar attendees contribute to the organizations before New Year’s Day, Thiel's foundation announced, the billionaire investor-philanthropist will contribute another dollar, up to a limit of $1,000 per organization per attendee. If everyone who attended Thiel’s so-called "Breakthrough Philanthropy" event gives a full $8,000, Thiel could be on the hook for a lot of money. My own rough estimate is that 200 people were on hand - and 200 times $8,000 comes to $1.6 million

Breakthrough Philanthropy - Thiel Foundation event

Peter Thiel did a good job of setting up the framing for these investments in brief final comments. He acknowledged that many of these ideas struck many in the philanthropy field as weird. But, he drew a distinction between incremental change and breakthrough change (he used the words "extensive" and "intensive"). Extensive change is going from something that works at one scale and bringing it up to a larger scale. He pointed out that it's much harder to go from zero to one, than it is to go from one to many. He's looking for those breakthrough opportunities that will have a major impact. But, that means you have to bet on a lot of unusual, "weird" ideas, to see one or two that have that kind of revolutionary impact. There aren't many philanthropists that explicitly endorse a strategy where the majority of their grants are likely to not be successful. But, if you have a heightened appetite for risk, the frame changes. What if only one of these groups gets revolutionary change going that changes society on a big scale? Probably a pretty good return on investment.

That last comment is a good description of investing in startups, the work of venture capital. A few big home runs and a lot of failures - and the world changes as a result of the successes. The field of institutional philanthropy would benefit from more of that way of looking at things and a good deal less of the sort of stolid, unimaginative endowments that lead to dead names carved on new buildings.

The viewpoint of researchers in the mainstream of biogerontology is that they have demonstrated slowed aging in a wide range of animals, this is the best they've managed so far, and therefore the research community should be first of all working to do more or less exactly the same thing in humans: "Over the last two centuries, there has been a significant increase in average lifespan expectancy in the developed world. One unambiguous clinical implication of getting older is the risk of experiencing age-related diseases including various cancers, dementia, type-2 diabetes, cataracts and osteoporosis. Historically, the ageing process and its consequences were thought to be intractable. However, over the last two decades or so, a wealth of empirical data has been generated which demonstrates that longevity in model organisms can be extended through the manipulation of individual genes. In particular, many pathological conditions associated with the ageing process in model organisms, and importantly conserved from nematodes to humans, are attenuated in long-lived genetic mutants. For example, several long-lived genetic mouse models show attenuation in age-related cognitive decline, adiposity, cancer and glucose intolerance. Therefore, these long-lived mice enjoy a longer period without suffering the various sequelae of ageing. The greatest challenge in the biology of ageing is to now identify the mechanisms underlying increased healthy lifespan in these model organisms. Given that the elderly are making up an increasingly greater proportion of society, this focused approach in model organisms should help identify tractable interventions that can ultimately be translated to humans."

Link: http://rstb.royalsocietypublishing.org/content/366/1561/99.long

Thoughts on engineered longevity are boxed into the standard, simplistic media viewpoint at Washington Examiner - everything is politics, and politics supposedly looks like this: "The right's reaction, I predict, will be to call for a moratorium on such innovations until we can determine whether life-extension therapies are 'playing God.' The playing God argument is, well, played out. If keeping people alive longer through conventional means isn't playing God, there is nothing categorically different about introducing breakthroughs that prevent age related illnesses to begin with. I dare say, people who believe in the sanctity of life will do well to consider the benefits of life-extending technologies for humanity. After all, as I suggest above, driving people into black markets is no way to enforce morality. And driving people into the grave because of some errant idea about God's plan doesn't do justice to what God's plan might actually be (i.e. that it may include life extension therapy). The left's reaction will be no less predictable. The left will say we should have a moratorium on the technology until we can figure out how to give everyone 'access' and quell Malthusian concerns about resource depletion and overpopulation (which will be unfounded). They will lament the gap between the poor short-livers and the rich long-livers. Then they'll try to cast life extension as a 'public health' good in order to socialize it, regulate it and ration it. This would be a grave mistake - one as serious as if we'd said people have a basic right to mobile devices. Socializing mobile technology would not only have retarded its development, but it would have limited its uptake. Almost everyone has a cellphone today, even though they didn't in 1990. Markets have meant better, faster and cheaper tech for the masses over time. It will be no different for life-extension therapies if they are left primarily to market forces."

Link: http://washingtonexaminer.com/blogs/opinion-zone/2010/12/get-ready-fountain-youth-near

It is sometimes easy to forget just how recently the more important discoveries in the genetics of longevity occurred. The concept that aging is very plastic, regulated by metabolic signaling pathways, sped and slowed by environmental circumstances, and considerably slowed by specific mutations in a few genes, has only really taken hold over the past fifteen years. This is a time of great change in the science of aging, even if progress seems glacial to those of us waiting on the practical applications of research: enhanced human longevity.

Today I'll point out a look back at the discovery of the importance of the insulin / insulin-like growth factor-1 (IGF-1) pathway in the regulation of aging. If you have an interest in how the mainstream of aging research moves forward behind the scenes, you should find this an entertaining read.

The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing

This article describes the discovery of a genetic pathway that regulates ageing. In spite of the fascinating qualities of the ageing process, such as its remarkably different pace in different species, until the last few decades ageing was not thought to be subject to any active regulation. Now we know that the rate of ageing is indeed subject to regulation, by classical signalling pathways. These pathways link the ageing rate to environmental and physiological cues, and may even underlie its diversification during evolution. At the heart of these pathways are stress and metabolic sensors such as insulin and IGF-1 hormones

...

At the time, ageing was generally thought to be a hopelessly intractable, even futile, problem to study. We just wear out; that's it. Fortunately, because of my experience I had come to expect that biological phenomena that seemed to happen haphazardly might well turn out to be controlled by the genes. ... Not only was ageing thought to be merely a passive, entropic process, evolutionary biologists had argued forcefully that ageing could not be regulated. For example, they felt that mechanisms for regulating ageing would have no way to evolve, as ageing takes place after reproduction. These theories were thought provoking, but to my mind, they had the effect of discouraging searches for regulatory genes. It seemed to me, a molecular geneticist from the outside, that one should keep an open mind and just have a look. So I saw the analysis of ageing as a fantastic opportunity to explore the unknown and perhaps discover something new and important.

It is an interesting account, all told. But the more things change, the more they stay the same: the "aging is plastic and regulated" camp back then were the heretics in the research community. Now that they have overturned the old guard and are at the head of the field, from the point of view of the success of their theories and supporting evidence, they have become the new old guard. They are focused on metabolic alteration and slowing aging as the only viable path forward: from their point of view it is self-evident that since aging is regulated, we must change the regulation, and since it is a matter of regulation, all we can do is slow things down.

The new heretics are people like Aubrey de Grey and other folk who advocate that (a) gerontologists should stop denying the moral imperative to work towards therapies for aging, and act more like the cancer research community and less like people who look but don't touch, and (b) repair-based approaches to engineered longevity are far superior: capable of reversing aging and helping people who are already old, and also easier to develop based on our present state of knowledge.

It is in all our interests for the new heretics to overturn the dominance of metabolic manipulation and for their repair-based approach to ascend to the head of the field as soon as possible. It's the only way we're likely to see radical extension of the healthy human life span within our lifetimes, and it's the only way we're going to see our frailties and ill-health reversed by rejuvenation medicine when we are old.

Better repair after major damage is a step below preventative repair beforehand, but it's an improvement over the present state of affairs: "A new technique that jump-starts the growth of nerve fibers could reverse much of the damage caused by strokes ...This therapy may be used to restore function even when it's given long after ischemic brain damage has occurred. ... Currently doctors can do little to limit stroke damage after the first day following a stroke. Most strokes are ischemic (caused by blood clots). A drug called tPA can limit damage but must be given within the first three hours for the greatest benefit -- and most patients do not receive treatment within that time frame. [Researchers] report on a treatment called anti-Nogo-A therapy. Nogo-A is a protein that inhibits the growth of nerve fibers called axons. It serves as a check on runaway nerve growth that could cause a patient to be overly sensitive to pain, or to experience involuntary movements. (The protein is called Nogo because it in effect says "No go" to axons.) In anti-Nogo therapy, an antibody disables the Nogo protein. This allows the growth of axons in the stroke-affected side of the body and the restoration of functions lost due to stroke. ... Nine weeks after their stroke, six rats received anti-Nogo therapy, four rats received a control treatment consisting of an inactive antibody and five rats received no treatment. Nine weeks later, rats that had received anti-Nogo therapy regained 78 percent of their ability to grab pellets. By comparison, rats receiving no treatment regained 47 percent of that ability."

Link: http://www.loyolamedicine.org/News/News_Releases/news_release_detail.cfm?var_news_release_id=973441324

An open access paper: "In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial metabolic and cellular features of long-lived families resemble those in animals for whom the lifespan is extended by applying genetic manipulation and, especially, dietary restriction. Candidate gene studies in humans support the notion that human orthologues from longevity genes identified in lower species do contribute to longevity but that the influence of the genetic variants involved is small. Here we discuss how an integration of novel study designs, labour-intensive biobanking, deep phenotyping and genomic research may provide insights into the mechanisms that drive human longevity and healthy ageing, beyond the associations usually provided by molecular and genetic epidemiology. Although prospective studies of humans from the cradle to the grave have never been performed, it is feasible to extract life histories from different cohorts jointly covering the molecular changes that occur with age from early development all the way up to the age at death. By the integration of research in different study cohorts, and with research in animal models, biological research into human longevity is thus making considerable progress."

Link: http://rstb.royalsocietypublishing.org/content/366/1561/35.long

Via Next Big Future, some thoughts from William Andregg, CEO and founder of Halcyon Molecular:

Question: How do your views on longevity and life extension compare with those of Aubrey de Grey and Ray Kurzweil?

Answer: Parts of SENS urgently should be funded and tested. That being said, I work on sequencing and not on SENS, because our approach to curing aging is first to turn biology into an information science - actually getting to untangling the morass of metabolism that SENS does an end run around. I believe we can get to a complete mechanistic understanding of human biology in only a few decades, which is a timeline more like Kurzweil’s. On the other hand, if SENS were being vigorously pursued today, it might save millions of lives before the total understanding approach avails us. It is good to have multiple bets.

As for Kurzweil, maybe this isn’t fair, and I’d like to hear his thoughts on it, but I’m afraid his books demotivate people who would otherwise contribute to the cause, maybe by giving the impression to some that the Singularity is not only coming, but actually inevitable. Eat right, exercise, take these pills, and don’t worry - those smart hardworking scientists over there will solve everything for you. In contrast, a great thing about Aubrey as a leader is that he harangues people to actually get off their asses and make a contribution.

We might not survive the next twenty years. We may never cure aging. There is nothing inevitable about our success. Everyone who is talented enough to make a contribution should be trying to help, on all fronts, by any ethical means, like it’s life and death - because it is.

Which is well said. The future is what we make it to be - if we sit back and make nothing of it, then we will all suffer horribly, become frail, and die from the same causes and at the same ages as our parents. It is a stark choice: the potential of lives of centuries of good health on the one side, and the certainty of the abyss upon the other.

As I have been known to mention here and there, SENS and related repair-based strategies for reversing aging are the direct and fastest path to the defeat of age-related suffering, frailty and death. Other roads in the life sciences will get there in the end, but that end will arrive decades too late to help those of us in middle age who are reading this today. If we collectively fail to soon build SENS into a research community to rival institutional cancer science in scope and ambition, then many, many millions of lives will be lost as a consequence - our own a few drops amidst the tide. Fifty million deaths each year, repeated for every year that rejuvenation therapies remain unrealized.

It takes a peculiar kind of societal madness to support an entire industry of people devoted to telling us solemnly just how bad, terrible, and wrong it would be to use medicine to live longer. Here is an open access paper in which a bioethicist bemoans the inevitability of extended healthy life - calling it tragic: "Biogerontology is sometimes viewed as similar to other forms of biomedical research in that it seeks to understand and treat a pathological process. Yet the prospect of treating ageing is extraordinary in terms of the profound changes to the human condition that would result. Recent advances in biogerontology allow a clearer view of the ethical issues and dilemmas that confront humanity with respect to treating ageing. For example, they imply that organismal senescence is a disease process with a broad spectrum of pathological consequences in late life (causing or exascerbating cardiovascular disease, cancer, neurodegenerative disease and many others). Moreover, in laboratory animals, it is possible to decelerate ageing, extend healthy adulthood and reduce the age-incidence of a broad spectrum of ageing-related diseases. This is accompanied by an overall extension of lifespan, sometimes of a large magnitude. Discussions of the ethics of treating ageing sometimes involve hand-wringing about detrimental consequences (e.g. to society) of marked life extension which, arguably, would be a form of enhancement technology. Yet given the great improvements in health that decelerated ageing could provide, it would seem that the only possible ethical course is to pursue it energetically. Thus, decelerated ageing has an element of tragic inevitability: its benefits to health compel us to pursue it, despite the transformation of human society, and even human nature, that this could entail."

Link: http://rstb.royalsocietypublishing.org/content/366/1561/108.long

Investor Peter Thiel has put millions into rejuvenation biotechnology research, you might recall. Here he's calling for others to show the same foresight: "Silicon Valley billionaire Peter Thiel worries that people aren't thinking big enough about the future. So he's convening an unusual philanthropic summit tonight at which he will introduce other wealthy tech figures to nonprofit groups exploring such futuristic - some might say 'far out' - ideas as artificial intelligence, the use of 'rejuvenation biotechnologies' to extend human life, and the creation of free-floating communities on the high seas. 'We're living in a world where people are incredibly biased toward the incremental,' said Thiel, explaining that he wants to challenge his peers to pursue more 'radical breakthroughs' in their philanthropy by supporting nonprofit exploration of technological innovations that carry at least the promise of major advances for the human condition. 'Obviously there are a lot of questions about the impact of these things,' he added. 'If you have radical life extension, that could obviously lead to repercussions for society. But I think that's a problem we want to have.' The list of expected attendees is closely guarded, but aides said it includes such figures as venture capitalist Pierluigi Zappacosta, a co-founder of Logitech, and Infoseek founder Steve Kirsch. ... Other presentations will be made by representatives from Humanity Plus, which promotes the idea that high-tech prosthetics and other scientific advancements can enhance human physical capabilities; the Foresight Institute, which focuses on the potential for medical and manufacturing advances through nanotechnology, or building things at the atomic level; and the SENS Foundation, which sponsors research into prolonging life by reversing the damage caused by normal aging."

Link: http://www.mercurynews.com/business/ci_16792615

Via Accelerating Future, I see that the next meeting of SENS Foundation supporters in Los Angeles will be held this coming Friday. As you may know, the Foundation advocates, funds, and organizes research into methods of reversing the course of aging by repairing the identified biological causes of aging.

On behalf of the SENS Foundation I am excited to send you this invite to our next SENS Foundation Los Angeles Meeting on Friday, December 10th @7pm. This time we will hold the meeting at Giant Studios, home of Lord of The Rings, Avatar, Narnia, Tin Tin, The Polar Express, etc. This impressive facility is one of the leading Motion Capture studios in the world.

We will be delighted to have three of the Foundation’s co-founders, Mike Kope, Aubrey de Grey and Sarah Marr with us, a talk by Keith Murphy (CEO Organovo), Paul Hynek (of Giant Studios) and inevitably “me” :-)

A glance at our tentative schedule for the night:

7:00 pm: A talk by Aubrey de Grey explaining SENS and the work of the Foundation
7:30 pm: An introduction to the SENS Foundation staff and a break for drinks
8:00 pm: Talks from Sarah Marr, and Keith Murphy
9:00 pm: A tour of Giant Studios, drinks, and a chance to mingle

I hope you join us and please feel free to bring your friends along. Be punctual so you don’t miss Aubrey! It will be a great night I promise.

Please RSVP.

Event location:

Giant Studios
12615 Beatrice Street
Los Angeles, CA 90066
Tel: (310) 839-1999

Maria Entraigues
maria.entraigues@sens.org

If you want to learn more about volunteering for the SENS Foundation - to help in creating medical technologies that greatly extend healthy human longevity - then you might visit the Foundation website.

On a number of fronts, researchers are within reach of making cavities in teeth a thing of the past: scientists "have deciphered the structure and functional mechanism of the glucansucrase enzyme that is responsible for dental plaque sticking to teeth. This knowledge will stimulate the identification of substances that inhibit the enzyme. Just add that substance to toothpaste, or even sweets, and caries will be a thing of the past. ... The main cause of tooth decay, the bacterium Streptococcus mutans, also uses this enzyme. Once attached to tooth enamel, these bacteria ferment sugars releasing acids that dissolve the calcium in teeth. This is how caries develop. ... [Researchers expect] that specific inhibitors for the glucansucrase enzyme may help to prevent attachment of the bacteria to the tooth enamel. Information about the structure and functional mechanism of the enzyme is crucial for developing such inhibitors. Thus far, such research has not been successful ... The various inhibitors studied not only blocked the glucansucrase, but also the digestive enzyme amylase in our saliva, which is needed to degrade starch." It's just a matter of time and funding before a suitable inhibitor is found.

Link: http://www.sciencedaily.com/releases/2010/12/101203101341.htm

Opponents of engineered longevity often put forward a false choice between quality of life and length of life. But medicine of the future will give us both: "one of the ten most-read articles on the BBC news website at the moment is a piece by Joan Bakewell suggesting that greater longevity may not be desirable. It's a superficially thoughtful commentary, but in truth it just runs through a series of standard knee-jerk reactions, most of which don't stand up to much scrutiny. Firstly, there is the implicit assumption that any extra years of life are bound to be of extremely low quality, due to physical and mental frailty. But one thing that actually unites almost all scientists in this area - from the mainstream ones like S Jay Olshansky who seek to slow the aging process by a few years, to the 'heretics' like [Aubrey] de Grey who seek to conquer it entirely - is that they don't think an increased lifespan would be beneficial unless 'healthspan' is boosted to an equivalent (or more likely greater) degree. There's always the danger of unintended consequences, of course, but there's no reason to fear the stated goal of the research. ... Finally, there's the general sense in Bakewell's article that 'a fuller life is better than a longer one'. This is a superficially attractive philosophy, but once again, it looks somewhat different if you just tweak the implicit parameters a little. What if the 'fuller life' lasted a mere twenty years, and the 'longer life' lasted eighty? Would anyone seriously suggest that the fullness of the twenty years entirely makes up for the tragedy of the lost sixty years? Some might, but it would be a far tougher case to make, simply because of our perceptions of what a 'natural' lifespan is. And yet the span we fetishise as being optimal is just a random quirk of the stage of evolution we happen to be at - some species live much shorter lives than we do, other species much longer."

Link: http://scotgoespop.blogspot.com/2010/12/joan-bakewells-false-choice-on-life.html

I noticed a very interesting open access paper today, a good example of the sort of barnstorming experimentation in stem cell science that is taking place now that near-every laboratory can create pluripotent stem cells easily and at low cost. In essence the researchers did the following:

• Start with fibroblast cells that have bad, damaged mitochondria
• Produce induced pluripotent stem cells (IPSCs) from the fibroblasts
• Then direct the IPSCs to differentiate into more fibroblasts
• Lo and behold, the new fibroblasts have good, functional mitochondria

It's more complicated than that, of course, and the researchers add a list of caveats as long as your arm in the discussion - they don't have a full understanding of what is happening here and why. Their summary:

We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1) that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2) the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturation found in a developing mammal.

Lack of understanding aside, there is clearly something interesting going on. If there is a mechanism there to be exploited, perhaps it may be usefully applied to the development of stem cell therapies for the aged. One of the big potential issues with the whole field of tissue engineering and stem cell medicine is that old people have old stem cells and old biochemistries: damaged, dysfunctional, and problematic. But at the same time, old people are those who need these therapies the most. Therefore we want to know that there are ways to include the repair of cellular damage in any potential stem cell therapy or tissue engineering project - an extra step in between taking the source cells from the patient and then returning the modified therapeutic cells.

As regular readers might recall, one of the many aspects of an aged biochemistry is that the mitochondria, the swarming power plants of the cell, are damaged and dysfunctional to some degree. This accumulating mitochondrial damage is in fact one of the causes of aging, and the short explanation as to why it happens is that the cell's recycling mechanism cannot properly identify and destroy certain forms of damaged mitochondria. So it is interesting to see a process demonstrated - even a fairly radical process - whereby a cell can reset its mitochondria to a fully functional state.

Like a number of the things I point out here at Fight Aging!, I think this has no direct and immediate application to the reversal of aging. You can't revert and re-differentiate all your cells, or at least not if you want to continue living. For repair of mitochondria throughout the body, you should be looking in the direction of protofection research, or the mitoSENS project - or anything else mentioned in the summary of mitochondrial repair research posted earlier this year. But that said, it is very encouraging for the future of tissue engineering and regenerative medicine to see this sort of cell rejuvenation demonstrated. It is beginning to seem as though the hurdles imposed by an age-damaged biochemistry might not be so great after all - see this report from earlier in the year, for example:

"Regardless of the gender or age of the patient, or of diabetes, we were able to isolate in all of them a pool of functional cardiac stem cells that we can potentially use to rescue the decompensated human heart."

The mainstream of longevity research is the domain of metabolic exploration and manipulation: scientists in search of a better human metabolism that will age at a somewhat slower rate. This is a realm apart from the minority efforts to repair biological damage and thereby reverse aging. Here is an example of the sort of metabolic research presently taking place: "scientists report finding a molecular 'switch' that can 'turn off' some cellular processes that are protective against aging and metabolic diseases. While more research is needed, the findings may open doors for new drug treatments to halt or slow development of metabolic diseases like type 2 diabetes or heart disease. ... [Researchers] focused on the role of the protein SMRT (silencing mediator of retinoid and thyroid hormone receptors) in the aging process. They found aged cells accumulate more SMRT and wanted to see if SMRT increases the damaging effects of oxidative stress on mitochondria, the cell component that converts food and oxygen into energy and powers metabolic activities. Oxidative stress is a cellular process that damages DNA, protein, and other cell functions and can lead to age-related diseases such as type 2 diabetes, Alzheimer's, Parkinson's, and atherosclerosis. ... in older animals SMRT acts like a 'switch,' turning off the protective cellular activities of proteins known as peroxisome proliferator-activated receptors (PPARs). PPARs help regulate genes that promote fat burning to maintain lipid (blood fat) balance and reduce oxidative stress. The researchers were able to reduce the negative effects of oxidative stress by giving antioxidants or drugs known to turn the protective activities of PPARs back on."

Link: http://www.eurekalert.org/pub_releases/2010-11/hsop-sdm113010.php

Egalitarianism is a dangerous philosophy - as practiced throughout history it seems to involve a lot more tearing down and destruction than building up and progress. We are hardwired to manage equality in small hunter-gather groups, but these same impulses in a large society lead to hideous end states like the old Soviet Union. Despite this history, egalitarianism remains very popular, and here is an egalitarian view of the imperative to develop technologies of engineered longevity: "Most egalitarians will not have the intuition that tackling aging is a requirement of equality. Why not? For starters, most egalitarians will assume that, because aging is universal, there is no inequality that warrants mitigating... end of story. But this assumption is false. While it is true that everyone chronologically ages at the same rate (i.e. we each age 1 year every 12 months), there is a significant variation in the rate of biological aging. That is, the rate at which we experience the molecular and cellular decline that gives rise to morbidity and, ultimately, death. So there is an inequality at stake here. But, our egalitarian might retort, this inequality is trivial. Again, this assumption is false. The stakes are very significant indeed. We are talking about an extra 20-30 years of health for some (rare) fortunate individuals. And what explains their exceptional health and longevity is not their exceptional lifestyles, but rather the fact that they have inherited longevity genes. ... I think that is the basis of a pretty solid case for supporting the aspiration to retard human aging. Getting to that conclusion requires a lot more work than simply appealing to some basic egalitarian intuitions. But that simply illustrates another important point - egalitarians ought to invest less of their energies fine tuning their egalitarian intuitions and more time and energy in understanding the empirical realities of the world (especially the human species)."

Link: http://colinfarrelly.blogspot.com/2010/12/longevity-genes-video-and-some-thoughts.html

The next Humanity+ conference will be held at Caltech on December 4th and 5th, just a couple of days from now. The second session is on the topic of radical life extension, and will feature researchers Michael Rose and Aubrey de Grey, amongst other familiar faces. I see that h+ Magazine is running a selection of promotional short articles on the conference, including one covering the radical life extension session:

The term "biological immortality" doesn't mean what you may think - it doesn't mean living forever, but merely "the absence of a sustained increase in rate of mortality as a function of chronological age." That is, you've reached biological immortality if your "personal death odds" - your chance of dying during a given random day, month or year - has stopped increasing.

...

Professor Michael Rose from the University of California at Irvine suggests that humans and other animals generally reach a plateau of biological immortality after a certain age - after this point, they're not really "aging" any more, as their personal death odds [remain high but constant]. ... He suggests that via doing research combining experimental evolution on model organisms (such as fruit flies and mice), genomic data analysis and artificial intelligence, one may be able to figure out personalized medicines and other therapies that will help one reach the plateau even sooner [and thereby live longer in good health].

...

On the other hand, Dr. Aubrey de Grey from the SENS Foundation (SENS = Strategies for Engineering Negligible Senescence) is unsure that the biological immortality concept is all that relevant to human aging. Like many biologists, he suspects that the data apparently supporting an immortality plateau in humans can actually be explained via the heterogeneity of data regarding aging and death from different populations. This is a subtle statistical issue, but it has practical implications. Dr. de Grey suggests that a large percentage of aging is due to accumulated damage in the body, and he describes an impressive variety of methods for alleviating or preventing this damage.

If accumulated damage is the main culprit behind aging, then one would not expect to see an immortality plateau - naively, one would probably expect to see the individual’s personal death odds keep increasing, as damage accumulated. So de Grey's focus on accumulated damage fits perfectly with his skepticism about the relevance of biological immortality to human aging.

On the issue of biological immortality as a steady mortality rate in old humans, I have a foot in both camps. I think there is good reason to believe that this fascinating phenomenon does exist, but it is absolutely irrelevant to the long-term future of longevity science. If we are focused on repairing the biological damage that causes aging, which is the only approach likely to meaningfully extend the lives of those of us reading this today, then we don't really care all that much about the demographics of the extremely old. Instead we just work as fast as we can to build the technologies that can safely reverse the state of being age-damaged and frail, and refrain from stopping to smell the flowers along the way.

Another benefit of exercise: "exercise increased the number of satellite cells (muscle stem cells) - a number which normally declines with aging. The researchers believe that a decline in the number of these cells and their functionality may prevent proper maintenance of muscle mass and its ability to repair itself, leading to muscle deterioration. Comparing the performance of rats of different ages and sexes, they found that the number of satellite cells increased after rats ran on a treadmill for 20 minutes a day for a 13-week period. The younger rats showed a 20% to 35% increase in the average number of stem cells per muscle fiber retained - and older rats benefited even more significantly, exhibiting a 33% to 47% increase in stem cells. ... Endurance exercise also improved the levels of 'spontaneous locomotion' - the feeling that tells our bodies to just get up and dance - of old rats. Aging is typically associated with a reduced level of spontaneous locomotion. The combination of aging and a sedentary lifestyle significantly contributes to the development of diseases such as osteoporosis, obesity, diabetes and cardiovascular diseases, as well as a decline in cognitive abilities. If researchers can discover a method to 'boost' satellite cells in our muscles, that could simulate the performance of young and healthy muscles - and hold our aging bones in place."

Link: http://www.aftau.org/site/News2?page=NewsArticle&id=13421

From Singularity Hub: "the US FDA has granted approval for clinical trials for a therapy derived from human embryonic stem cells. Advanced Cell Technology (ACT), a Massachusetts based bio-firm, recently announced that they had secured approval for human trials of their retinal pigment epithelial cells to treat Stargardt's Macular Dystrophy. SMD causes blindness, generally among youths 10 to 20 years in age, and affects less than 200,000 people in the US. The recently approved trials will only involve 12 patients, and are looking primarily to establish that using the ACT cells is safe. There is hope, however, that the vision of those treated could be improved or restored. In the longer term a success for embryonic stem cells here could lead to treatments for other forms of blindness. Yet as exciting as this study may be it's also a sad reminder of how long it has taken to get embryonic stem cells approved for human trials. ... I'm also frustrated, as I know many of you are as well, that promising stem cell technologies are taking so long to get to patients. Both Geron and ACT had remarkable success in their animal models. Geron got mice walking again after spinal injury and ACT had 100% success with getting rodents to grow new retinal cells after treatments (100 percent!). It's disappointing to think that either a) the FDA doesn't recognize the overwhelming potential of these treatments and isn't willing to help them move along as fast as possible OR b) has been helping them, and this is as fast as it possibly can get."

Link: http://singularityhub.com/2010/11/24/fda-approves-acts-embryonic-stem-cell-trial-for-blindness-should-we-get-excited/

An appreciation of reliability theory is a good way to better put into context ongoing research into the cellular and molecular mechanics of aging. Reliability theory was developed to better predict the failure rates and times to failure of complex systems consisting of many redundant components - such as ships, electronic circuitry, or even we humans:

The failure of mechanical devices such as ships, trains, and cars, is similar in many ways to the life or death of biological organisms. Statistical models appropriate for any of these topics are generically called "time-to-event" models. Death or failure is called an "event", and the goal is to project or forecast the rate of events for a given population or the probability of an event for an individual.

...

Reliability theory of aging provides an optimistic perspective on the opportunities for healthy life-extension. According to reliability theory, human lifespan is not fixed, and it could be further increased through better body maintenance, repair, and replacement of the failed body parts in the future.

Modeling a human being as a collection of many, many redundant parts (representing cells, or clusters of cells) produces results that match the observed demographics of aging and life expectancy very well. This approach is further supported by the observed benefits of increased autophagy and apoptosis on health and longevity.

Autophagy is, broadly speaking, the process by which your cells recycle damaged components. Cells are packed full of building blocks dedicated to specific tasks, and few of them are designed to last. The average cell is a little powerhouse of dynamic destruction and construction, tearing down and rebuilding organelles left and right.

...

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death.

Both autophagy and apoptosis act to remove broken components of the body before they can cause harm. If either process is globally impaired, then the result is what amounts to faster aging: a more rapid accumulation of cellular damage that then itself causes further damage. Not a good thing. Unfortunately, impairment of apoptosis is exactly what we see in aging, as a recent review paper notes.

Apoptosis and aging: increased resistance to apoptosis enhances the aging process

Apoptosis is the guardian of tissue integrity by removing unfit and injured cells without evoking inflammation. However, apoptosis seems to be a double-edged sword since during low-level chronic stress, such as in aging, increased resistance to apoptosis can lead to the survival of functionally deficient, post-mitotic cells with damaged housekeeping functions. [These] senescent cells are remarkably resistant to apoptosis, and several studies indicate that [immune system actions] can enhance anti-apoptotic signaling, which subsequently induces a senescent, pro-inflammatory phenotype during the aging process. ... We will discuss the molecular basis of age-related resistance to apoptosis and emphasize that increased resistance could enhance the aging process.

Given all the evidence, the role of immune system dysfunction (and the resulting chronic inflammation it causes) in aging appears to be fairly important. It causes disarray in many of the important biological processes that evolved to keep our bodily systems running well, and this and other contributions to degenerative aging eventually add up to bring frailty and then death.

Can autophagy and apoptosis be enhanced in the near future to bring general benefits to health and longevity? Quite possibly: calorie restriction mimetic research may eventually result in designer drugs intended to enhance autophagy, given the importance of autophagy to the benefits produced by calorie restriction. You might look at the work on spermadine as an example of a first step along this path. Conceptually similar work on apoptosis takes place in the cancer research community, where apoptosis is viewed as a dominant mechanism of cancer suppression. The bottom line is that these are signaling challenges: the body is capable of boosted autophagy and apoptosis in response to certain environment conditions, and researchers can in principle learn how to issue the signals to trigger that same boost without unwanted side-effects.

Regardless, it is true that aging is marked by uneven changes in many complex, interacting processes - such as the immune system's response to circumstances, programmed cell death signaling, and other related line items. Nothing is simple when you're down at the level of signaling systems and cells, and it's easy for the eyes to glaze over when reading the latest research and trying to put it into context. This is where good models such as the reliability theory approach to aging can help: aging is, quite clearly, a matter of accumulating damage and failing redundancy in the components of our body. Bear that in mind, and you can't go too far wrong while thinking about the latest research results.

Type 2 diabetes is a lifestyle disease for nearly all people - for them, it is a choice to be fat, sedentary, and overfed, and thereby risk damaging consequences to long-term health. The costs are becoming well enumerated: "Despite medical advances enabling those with diabetes to live longer today than in the past, a 50-year-old with the disease still can expect to live 8.5 years fewer years, on average, than a 50-year-old without the disease. ... The analysis - based on data from the Health and Retirement Study (HRS) - found that older adults with diabetes have a lower life expectancy at every age than those without the disease. At age 60, for example, the difference in life expectancy is 5.4 years. By age 90, the difference is one year. ... the figures show a marked increase in the percentage of adults over age 50 with diabetes during the past decade: from 11 percent of non-Hispanic whites in 1998 to 18 percent in 2008, and from 22 percent of non-Hispanic blacks in 1998 to 32 percent in 2008. The report [also] found that, compared to older adults without diabetes, those with the disease are less likely to be employed and more likely to have other health problems, such as heart disease, depression, and disabilities that interfere with normal life activities. ... Diabetes currently afflicts 7.8 percent of the total U.S. population - 23.6 million people, including 5.7 million undiagnosed - but almost a quarter (23.1 percent) of individuals age 60 or older (12.2 million people)."

Link: http://www.geron.org/About%20Us/Press%20Room/Archived%20Press%20Releases/72-2010-press-releases/886-during-national-diabetes-awareness-month-new-report-ties-disease-to-shortened-life-expectancy

A good article on cancer stem cells : "The stem cell theory of cancer proposes that a relatively small number of rare stem cells drive tumor formation and progression. The majority of cancer cells, cancer stem cell (CSC) theory advocates say, can't sustain the tumor nor establish it elsewhere in the body; only CSCs are tumorigenic and have a metastatic phenotype. The CSC theory has significant implications for cancer research and therapy and may explain why treatments focused on reducing tumor mass by removing proliferating cells fail to eliminate tumors. Or maybe not. Despite a large number of publications supporting the existence of stem cells in tumors including human blood-cell derived cancers and solid tumors of the brain, breast, colon, pancreas, prostate, and skin, the issue of CSCs remains in serious contention. ... I think that there are some cancers that do clearly follow a cancer stem cell model, but it will be more complicated than what's been presented so far ... The existence of stem cells in tumors has been invoked to explain why some cancers keep going, no matter what chemotherapies or immunotherapies are used. Stem cells usually cycle slowly and thus are relatively insensitive to treatments aimed at stopping cell replication. CSCs are more resistant to conventional cancer drugs not only due to quiescence relative to cancer cells but also because they are characterized by increased expression of antiapoptotic proteins and drug efflux transports. Additionally, according to recent findings, they rapidly change antigen expression, making them unlikely targets for immunotherapies that target cell surface proteins."

Link: http://www.genengnews.com/analysis-and-insight/melanoma-cells-all-stem-cells-in-disguise/77899351/