The Biochemistry of Being Fit
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Being fit is good for the healthy longevity of components and systems within your body. Via the open journal Immunity & Aging, here is a look at fitness and the aging immune system: "Highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function ... elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels [a pro-inflammatory cytokine] were significantly lower than their sedentary peers. ... Of the various components of the immune system, T cells are the most sensitive to the effects of aging. Mitogen-induced T cell proliferation is usually reduced, and this may be the result from disruption of the well-balanced network of regulatory cytokines."

Link: http://www.immunityageing.com/content/3/1/9

Clueless Enthusiasm
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There is a widespread sense of enthusiasm for healthy life extension out there - but it is largely clueless enthusiasm, focused on things that don't matter in the grand scheme, are unproven, ineffective, or pushed by the health demagogue of the moment (who often happens to be selling you a product).

There are two sorts of clueless enthusiasm for healthy life extension; type 1 is focused on the now, the cricket who wants answers immediately, searches where the light is shining, and has no willingness to look to the future. People affected with this sort of clueless enthusiasm are actively engaged in deluding themselves - or allowing themselves to be deluded by others. Reality is harsh: while there are many simple things you can do for your health, all require work and sacrifice. There is no silver bullet, and there is no presently available way to greatly extend your maximum life span. There are any number of people willing to claim otherwise while taking your money, however.

In short, there is primary aging and there is secondary aging: there are methods of ameliorating the latter, and very little that affects the former. We're all on a clock, and burying your head in the sand of willful self-delusion isn't going to prevent your suffering and death in the decades ahead.

Primary aging is the gradual - and presently inevitable - process of bodily deterioration that takes place throughout life: the accumulation of biochemical damage that leads to slowed movements, fading vision, impaired hearing, reduced ability to adapt to stress, decreased resistance to infections, and so forth. Secondary aging processes result from disease and poor health practices (e.g. no exercise, smoking, excess fat and other forms of self-damage) and are often preventable, whether through lifestyle choice or modern medicine. The two categories are somewhat fuzzy at the borders by these definitions; we hope that advancing medical and biotechnology will move the known and understood aspects of primary aging into the secondary aging category as rapidly as possible.

Type 2 clueless enthusiasm is potentially more useful to those of us seeking support for scientific anti-aging research. The type 2 enthusiast does look to the future, but is just as ill-informed as the type 1 enthusiast when it comes to science, what will work and the best path forward. I stumbled over a recent column that I believe to be illustrative of the type:

"Fifty percent of Baby Boomers can live up to 100 and beyond."

He received a standing ovation when he boldly predicted genetic research on stem cells and cloning "will take us to 120 and beyond. Soon, we will be the Ageless Society."

While arguably over the top, such optimism is consistent with the Boomers' ever-present desire for youth and health. They eat better, exercise more and hope to benefit from furthur scientific breakthroughs.

The enthusiasm is there, but there is no substance nor understanding when it comes to the details. Enthusiasm without meaningful direction is just like investment without meaningful management - it doesn't matter how much support there is, because it's all being wasted. Like water poured on the ground, it soaks away without effect. You can put a waterwheel under a stream of water, however; this is what advocates for scientific, directed anti-aging research seek to do. We can harness the support of type 2 clueless enthusiasm - and turn it into clueful enthusiasm - by providing a plausible path forward to a future of longer, healthier lives. It all comes down to education, spreading the message and having the science to back it up.

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The Value of Progeria Research
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Ouroboros points out the greater value of progeria research beyond the development of a cure for these rare conditions: "Premature aging syndromes in model organisms and humans provide insight into the mechanisms of natural aging. To the extent that progerias represent true acceleration of wildtype aging processes, they also draw our attention to genes that might someday be targeted by lifespan-enhancement strategies. ... Farnesyltransferase inhibitors, a class of drugs originally developed to attack the Ras pathway in cancer, are showing great promise in reversing the nuclear abnormalities resulting from the underlying lamin A/C mutation [of progeria]." Aging cells share some of the same characteristics as progeroid cells; time will tell just how important this will be to the development of a working rejuvation toolkit.

Link: http://ouroboros.wordpress.com/2006/09/29/the-panoply-of-progerias/

Trends to Watch For In Biotechnology
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Randall Parker hammers on the important trends again: "Until recently, DNA methylation could only be studied one gene at a time. But a new microarray-based technique developed at Illumina enabled the scientists conducting this new study to simultaneously examine hundreds of potential methylation sites ... Some people argue that anti-aging therapies are a distant prospect because even at Moore's Law (which is a doubling time for computer power of about 18 to 24 months) rates of advance it will take a long time before biotechnology can reverse full body aging. ... But biotechnology can advance more rapidly than computer technology did because biotechnology is in the process of harnessing techniques first developed for the computer industry over a period of decades. ... This allows biotech to capture in a relatively short period of time the gains of decades of semiconductor technology. So I'm not surprised to read about sudden orders of magnitude increases in the ability to do biological experiments using silicon chips." Rapid trends towards faster, better and cheaper tools are driving the biotechnology revolution.

Link: http://www.futurepundit.com/archives/003755.html

The Ball and Chain
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What slows progress in scientific research? Some fairly direct pointers in these two recent articles:

Brain research requires rethinking:

In the past decade, funding of biomedical research has doubled, the human genome has been sequenced and the drug approval process has been speeded up considerably. But, disturbingly, the result has been virtually no new treatments for conditions of the brain.

"Why are there not more drugs?" Dr. Martin asked.

The reason is that a lot of pharmaceutical companies are more interested in producing blockbuster lifestyle drugs and "me too" medications that mimic their competitors' successful products than in investing in treatments for the likes of Alzheimer's and Parkinson's.

The regulatory system doesn't promote innovation, Dr. Martin said. And intellectual property (patent) laws promote secrecy and discourage collaboration, undermining the type of co-operation that is needed to tackle complicated brain conditions.

Your Genetic Future

One big question is how FDA will handle the changing paradigm. The agency is used to weighing a drug's side-effect profiles against the severity of the condition and the drug’s overall effectiveness. Highly targeted drugs, perhaps linked to a genetic test, call for a completely different regulatory mindset. Side effects may suddenly be verboten--and volumes of genetic data will be a stiff challenge to FDA’s reviewers.

How will the agency react? Probably slowly as it has so far, Galas says. The agency is underfunded, and that makes it difficult to keep up with current research trends. That uncertainty in turn makes investors nervous, potentially slowing the growth of the industry--and employment opportunities.

In anticipation of targeted medicines, pharmaceutical and biotechnology companies are increasingly performing genetic studies of clinical trial participants in hopes of identifying genetic profiles that predict therapeutic outcomes. A drug that only benefits 15% of participants might seem like a clinical failure--but if those respondents share a genetic profile, the drug might be admitted to the market with an accompanying genetic test.

But such data can be difficult to interpret, so it could even slow down an approval process. This could be a disincentive to doing such tests in the first place. Until FDA’s stance is clarified, pharmacogenomics will be a volatile and unpredictable business and career path. "Young companies trying to get into pharmacogenomics and personalized medicine are facing daunting challenges because of uncertainties with FDA and just the inherent difficulties of trying to change the paradigm to something where side effects are unacceptable," says Galas.

...

Despite these new opportunities, genetics remains a field defined by uncertainty, as both FDA and industry wrestle with questions of data analysis, side effects, and other issues. The uncertainty is likely to be a drag on job growth in medical genetics. "If you’re coming into the field now, the market for your type of jobs may not grow as fast as you had hoped," says Galas. "We always underestimate the impact of these types of technologies, but we also overestimate the speed at which they’ll be adopted. There’s going to be a huge need for people to do this work. The better the people and the more of them there are, the faster it will happen."

Large pharmaceutical companies will follow the safest profit-bearing line - which is determined by regulation they help shape to protect their business from competitors in the short term. At the same time, government employees are following their own political goals and urge to power with no regard to long-term negative effects on the regulated. The way in which those in charge of large companies and government employees collaborate to ruin progress for the many in the name of short-term gain for a few was recently clearly laid out (again) at Mises.org:

The Chicago School of economics favored and still favors the theory of "regulatory capture." Under this theory, an industry or some portions of an industry cultivate government to obtain laws and rules that favor the industry.

The government trades favors for what it wants. Politicians gain political contributions, side payments, and votes for being seen to control the industry. The industry captures the regulators. End of story.

North went much further. He called the first step of obtaining favors "baiting the trap." But matters do not stop there, he pointed out. The trap is set when the industry becomes comfortable with its subsidy, tax break, tariff, exclusive position, license, or whatever. It then begins to extract monopoly rents and to lower product quality.

This then leads to further steps such as public outcry and a government demand for the industry to police itself. Then come crisis, further regulatory intervention, and eventually a government stranglehold over the entire industry via a panoply of boards and price controls. This is when the trap is sprung. The market is replaced by government power and bureaucrats. Government, its aim being control, traps and captures the industry.

In the shorter term, the interest groups use the state against the public. In the longer term, the state and its bureaucrats rule the roost. In the end, the government bureaucracies expand. Paperwork and soft jobs rule the industry, innovation and competition are eclipsed, and the public suffers from poor product quality and high prices.

Medical research and development in Western-style democracies has slid into an unfortunate position: dragged down by regulation, and no let-up in sight in the growth of government and its willingness to impose costs upon progress towards better medical technologies. The true cost of this state of affairs lies in what you do not see: the vast and encompassing commercialization of new and innovative medicine that would be taking place in a free market - or even just one far less regulated.

If telomerase inhibitors were a new kind of computer chip, they would have been on every Wal-Mart pharmacy shelf and selling for ten dollars a bottle by now. ... In a free system, life insurance companies, consumer magazines, and other competing interests would provide medical databases. Maybe even the AMA would become a force for "truth-in-medicine," as it was to some degree before the creation of the FDA. Under common law but free of arbitrary regulation, drug development would be as fast as computer development. Cancer would be extinct and human beings would finally, really, own their own bodies.

How else will your future health be harmed because a large government allows the unscrupulous to manipulate their way to short-term gain at the cost of slow progress in medicine?

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Bionanotechnology Progresses
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Advanced medical technologies of the future will build upon the foundation of medical bionanotechnology under development today. As this Harvard release illustrates, the field is healthy and growing: "The Kavli Foundation and Harvard University have agreed to establish the Kavli Institute for Bionano Science and Technology (KIBST) ... The KIBST will seek to develop a deeper understanding of the functioning of life and biology at the nanoscale level by developing new tools and probes that marry microfabrication and microfluidics with high-resolution imaging. Our goals are to use such new techniques to probe the behavior of single molecules, cells, tissue, and organs; to gain a deeper understanding of the essential relationship between structure and function that controls all biology; and to combine structural and functional studies from the scale of single molecules to the scale of tissues and whole organs."

Link: http://www.news.harvard.edu/gazette/2006/09.28/09-kavli.html

Neurons and Deinococcus Radiodurans
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Very speculative science from LiveScience: what can be done with greater understanding of a regenerating microbe that shares some attributes in common with your cells? "This is the first case, I think, of a living cell that clinically dies - its DNA is chopped into little pieces and it has no metabolism - when desiccated, and yet, as long as it can reconstitute its genome, it reconstitutes its own life ... Radman believes his team's findings open up the possibility of resurrecting dead cells in our own bodies, specifically those in our brains. ... It allows us now, legitimately, to dream of bringing back to life dead or close to dead neurons. ... Like Deinococcus, neurons carry two - albeit slightly different - copies of their genomes: one from Mom and the other from Dad. In fact, all the cells in our bodies except sperm and egg contain two genome copies. Therefore, it's possible that one day scientists could resurrect dead neurons using repair mechanisms similar to those employed by Deinococcus, Radman said."

Link: http://www.livescience.com/humanbiology/060927_lazarus_cell.html

Blogging the Emerging Technology Conference
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Mike Treder has been blogging at the Emerging Technologies conference. Today he caught the breakout session on anti-aging research, in which the speakers were representative of the pro-longevity mainstream in gerontology and associated aging research. This is to say that they believe there is some small progress that can be made by manipulating genes and metabolism, they might be proponents of compression of morbidity over life extension, and reject out of hand any idea that faster progress is possible. From Treder's post:

In audience Q&A, Perls just called Aubrey de Grey a "goofball." Guarente says maximum lifespan (100-110 years) in humans probably will never increase, but the average will grow.

The best response to any number of comments like that is to (a) prove yourself right, and (b) get the job done more effectively. That process is getting underway at the Methuselah Foundation. To my mind, the worse thing you can do is to take the naysayers seriously. That way lies self-fulfilling prophecies; if you don't try, those who said it will never happen will certainly be right. Aubrey de Grey makes a good case for the better research path to extended healthy life spans; as more funding comes in, that case will just keep getting better.

Looking back at some thoughts on future conflict in anti-aging and longevity research, I see this sort of behavior as a good example of the way in which moderates or conservatives in a field feel they have to defend their legitimacy from potentially better, eclipsing solutions. It's just human nature, and we should take it as a good sign - the feeling of long-term funding being threatened by the advent of a new and more effective paradigm.

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More On Myostatin and Satellite Cells in the Aging Body
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You might recall work from earlier this year on the reduction in stem cell capabilities with aging; it suggested that stem cell populations decline, but their ability to regenerate does not. This contracts other research that suggests just the opposite; it should be interesting to see just how these results are reconciled in the end. Head to head contradictions are a strong sign of a field in flux and progress, carving understanding from the rock face of the unknown. At the present pace of stem cell research, we'll have an answer before the end of 2008.

Ouroboros pointed out a more recent paper that takes the "lots of stem cells, but declining ability to regenerate" side of the debate. This one also ties into myostatin and the promotion of muscle growth, something that has been put forward as a potential path to therapies for sarcopenia, or age-related muscle loss.

In young mice, lack of myostatin resulted in increased satellite cell number and activation compared to wild-type, suggesting a greater propensity to undergo myogenesis, a difference maintained in the aged mice. In addition, muscle regeneration of myostatin-null muscle following notexin injury was accelerated and fiber hypertrophy and type were recovered with regeneration, unlike in wild-type muscle. In conclusion, a lack of myostatin appears to reduce age-related sarcopenia and loss of muscle regenerative capacity.

This makes sense; you need active stem cells to grow muscle. So what is myostatin doing with the satellite stem cell population associated with muscle growth and repair? Answering that question might go a long way towards understanding what causes our stem cells to decline in activity with increasing age - and then to move on to safely preventing that fate.

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The Longevity Dividend Means Good Press
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Via the Mandurah Mail, an example of the way that recent changes in the public positions of high-profile gerontologists - such as those proposing the Longevity Dividend initiative - will lead to greater public support for all reputable scientific approaches to extending the healthy human life span: "We have reached an historical moment as scientists learn enough about ageing to postpone a wide range of fatal and disabling diseases. Interventions at a range of levels not only increase longevity in laboratory organisms, but can dramatically increase the duration of a disease-free life. We are now staring to identify the effect of hormones on the cellular pathways which influence ageing. ... In short we have found that extending the duration of health life in humans by slowing down the ageing process is now a very real scientific possibility." To hear this repeated loudly and clearly will have very positive effects on funding and science in the years ahead.

Link: http://mandurah.yourguide.com.au/detail.asp?story_id=512810

New Competitor for the MPrize
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The Methuselah Foundation announced the latest competitor for the MPrize for anti-aging research today: "Renowned epigenetics expert Dr. Craig A. Cooney of The University of Arkansas for Medical Sciences announced today that he is entering the competition to win the Methuselah Mouse Prize (Mprize). The Mprize, a scientific research prize aimed at encouraging scientists to find a way to reverse the aging process, is a primary activity of the Methuselah Foundation. The Mprize fund continues to grow and currently stands at more than $3 Million. Prizes will be awarded to research groups that can most successfully extend the lifespan of laboratory mice. ... Age-related diseases cause people to die much younger than they should,and from my research I foresee the possibility of slowing down or even curing these diseases. The Mprize is a great way to raise public awareness that the degeneration of aging is not inevitable -- I am looking forward to joining this effort."

Link: http://blog.methuselahfoundation.org/2006/09/university_of_arkansas_for_med.html

An Update on Bacterial Immortality
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While not directly relevant to healthy life extension in humans, it is, I think, important to remember that immortality surrounds us: the immortality of cells, bacteria, and the material from old individuals that grows into young children. Avoiding age-related degeneration and death is quite possible for biological systems - it is an unfortunate accident of physics that aging animals win out in the long haul of evolution. Here, more news from the New Scientist on the immortality - or not - of bacteria: "Ageing may be a strategic 'choice' for bacteria, since poor nutrition can lead to immortality in the single-celled organisms, a mathematical modelling study predicts. In 2005, their mortality was declared, after bacteria were shown to get old and die. That obituary is now looking premature. ... Organisms in nutrient-poor environments should be selected for symmetric division and therefore be immune to ageing. Bacteria on scanty nutrients grow slowly and presumably do not age - we know the possible mechanism now."

Link: http://www.newscientist.com/article/dn10154-ageing-may-be-a-lifestyle-choice-for-bacteria.html

Progress Towards the Brain Atlas
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Wired reports on a major milestone: "Scientists have mapped every gene in the mouse brain as part of Paul Allen's Brain Atlas project launched in 2001. ... The brain atlas combines cellular-resolution scans of the mouse brain with precise information about which genes are expressed where. ... We have essentially mapped each individual gene in the mouse brain, about 21,000 genes in all, down to the cellular level. ... The nonprofit's directors [will seek] additional sources of public and private funding for the next big step: scanning human brain tissue." The aging brain is one of the greatest challenges of the decades to come for healthy life extension science. If we are to benefit from future advances in repairing tissue and biochemical systems, we must become very, very good at repairing the aging brain. Tools like the Brain Atlas are the first step towards the understanding and technologies that will make this possible.

Link: http://www.wired.com/news/technology/medtech/0,71846-0.html

Thoughts for the Day
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A few pithy quotes from around the blogosphere:

"Anti-Life" Conservatism:

To paraphrase advocate Aubrey de Grey: Would widespread use of life-extension technology lead to problems? Obviously it would. Would it lead to any problems as serious as continuing to have a hundred thousand people die every day (the status quo)? No.

Silicon Valley's search for Fountain of Youth; Thiel joins Ellison in quest:

Oracle's Larry Ellison has also pushed science aggressively in this area, but we haven't heard much about his efforts of late. If there is a place where the Fountain of Youth will be discovered, it will probably be here. There is more health research, and money going to fund it, than anywhere else. And there are wealthy entrepreneurs who want to fund this sort of thing.

Money for anti-ageing research:

In the end, some of this comes down to personal values, and the overriding one from my viewpoint is that of retaining and exercising our capacities for as long as possible, rather than suffering the humiliations of decline and dependence. Despite all the pro-death propaganda around, I'm betting that this value will eventually prevail.

Transvision 2006 Review Part IV:

"If a thirty-year projection sounds like science fiction, it may be wrong. If it doesn't sound like science fiction, then it is definitely wrong." - Chris Peterson & Gayle Pergamit

If you've picked up an interest in healthy life extension within the past couple of years, you might not be familiar with the work of the Ellison Foundation. It is fairly quiet in comparison to the more vocal folk and organizations in aging research and related fields.

The Ellison Medical Foundation supports basic biomedical research on aging relevant to understanding lifespan development processes and age-related diseases and disabilities. The Foundation particularly wishes to stimulate new, creative, research that might not be funded by traditional sources or that is often under-funded in the U.S.

You can find a most interesting debate (on video and in PDF format) in the archives of the sadly defunct SAGE Crossroads website. Aubrey de Grey talks timelines for anti-aging research with Richard Sprott of the Foundation; you should take a look while it is still available online.

If pushed to make a categorization, I'd put the Ellison Foundation on the conservative side of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, but to the adventurous side of the Longevity Dividend crowd.

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Better Tools, Faster Results
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AScribe provides a sense of the sort of infrastructural improvements taking place in the field of biotechnology: scientists "have discovered a new technique to let them watch, visualize and precisely measure a key oxidant in animal cells ... In the past, our techniques for measuring or understanding superoxide were like blindly hitting a box with a hammer and waiting for a reaction. Now we can really see and measure, in real time, what's going on in a cell as we perform various experiments ... they have used the new technique to learn as much in the past three months about the basic cell processes as they did in the previous 15 years ... This will enable labs all over the world to significantly speed up their work on the basic causes and processes of many diseases, including ALS, arthritis, diabetes, Parkinson's disease, Alzheimer's disease, heart disease and others. And it should be especially useful in studying aging, particularly the theory that one cause of aging is mitochondrial decay."

Link: http://newswire.ascribe.org/cgi-bin/behold.pl?ascribeid=20060925.151734

Willful Ignorance Amidst Progress and Plenty
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There's a foolish fellow who thinks science is basically over and done with, or at least fairly close to that point, and has been parlaying this silliness into a career of sorts. He has an article in a recent Discover. It's entertainment, I suppose, only he'd rather like you to take his nonsense seriously:

Argument: We are on the verge of a breakthrough in applied biology that will allow people to live essentially forever. The potential applications of biology are certainly more exciting these days than those of physics. The completion of the Human Genome Project and recent advances in cloning, stem cells, and other fields have emboldened some scientists to predict that we will soon conquer not only disease but aging itself. "The first person to live to 1,000 may have been born by 1945," declares computer scientist-turned-gerontologist Aubrey de Grey, a leader in the immortality movement (who was born in 1963).

Many of de Grey's colleagues beg to differ, however. His view "commands no respect at all within the informed scientific community," 28 senescence researchers declared in a 2005 journal article. Indeed, evolutionary biologists warn that immortality may be impossible to achieve because natural selection designed us to live only long enough to reproduce and raise our children. As a result, senescence does not result from any single cause or even a suite of causes; it is woven inextricably into the fabric of our bodies. The track record of two fields of medical research - gene therapy and the war on cancer - should also give the immortalists pause.

This is pretty sloppy science journalism, and makes no sense at all from a scientific point of view. Is the end result of natural selection naturally immune to human intervention? I don't think you have to look too far at all to be able to pitch that idea out with the trash. Does making the treatment of aging sound hard have anything to do with how hard it actually is, or how much scientists know about how to go about it, or how much work has already been accomplished, or how widespread present work is? Of course not; it's just the foolishness of one journalist with - it seems - little knowledge of the field he is discussing.

As I understand the principle thrust of his argument, he is claiming that the slow rate of past progress towards specific goals of manipulating human biochemistry in manner X (rearranging the expression of your genes reliably and safely) make it unlikely we will ever be able to manipulate human biochemistry in manner Y (repairing the known cellular damage that lies at the root of aging). Amongst many problems with this argument is that manner Y - and manner X for that matter - are both perfectly compatible with the laws of physics as we know them. To deny the possibility of radical life extension by means of ongoing damage repair - via technologies presently under early investigation and development in laboratories around the world - is to deny physics. There is no middle ground: either you accept modern physics and all its consequences with regard to the plausibility of deliberately arranging atoms and molecules by design, or you don't.

The fellow's point of view with regard to ongoing work in biotechnology and aging research is slipshod and distant from the action. I have to assume that the rest of his work on other fields - which in many cases I am unqualified to judge - are just as shallow, slippery and ultimately vapid. I leave it as an exercise for the audience to pick at the errors; if entertainer this fellow is to be, you may as well get your money's worth.

The world is full of comedians, fools and dangerous people willing to stand up and tell us that black is white - looking for laughs, other fools, or a means to an end. Don't fall for it.

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Emerging Technologies Conference
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The Technology Review's Emerging Technologies Conference kicks off on the 27th. While it covers a wide range of technology, some of the speakers are involved in aging and healthy life extension research. "Leonard Guarente has been on the faculty of the Massachusetts Institute of Technology since 1981, currently as the Novartis Professor of Biology. Mr. Guarente formerly studied gene regulation in eukaryotes, then the mechanism of aging and its regulation using yeast and higher organisms. ... Thomas Perls is a physician and researcher in the study of aging at Boston University Medical School. [For] the past 11 years, Perls has directed the New England Centenarian Study ... Richard Weindruch is Professor of Medicine at the University of Wisconsin. In 1975, as a graduate student at UCLA, he began his interest in caloric restriction (which slows the aging process in diverse animal models). ... Mr. Westphal is CEO and Vice Chairman of Sirtris Pharmaceuticals, the leading sirtuin therapeutics company."

Link: http://www.technologyreview.com/events/tretc/

Thoughts on Superlongevity and Boredom
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Anne C. makes a good point on those who object to radical life extension by claiming boredom: "The plasticity of the human brain with regard to what it finds meaningful has already been conclusively demonstrated: depressed people often find 'everyday activities' unfulfilling and then find these activities fulfilling again following pharmacological treatment. Yet the treated and untreated individual are the same person: usually, even the depressed individual has a sense that things could 'seem' subjectively fulfilling or meaningful, and this can be a motivation for treatment. If a very long-lived person becomes bored, they could presumably [seek] treatment in the same manner as a present-day depressed person might. That is, when given the choice between a treatment that could help them find meaning in things again, and eternal nonexistence / oblivion, would most people honestly choose the eternal oblivion?" Some people are more prone to boredom than others; some people enjoy life more than others. There is always the choice not to live, or to seek change so as to live better.

Link: http://rationallongevity.blogspot.com/2006/09/quick-thoughts-on-superlongevity.html

Calcineurin, NFAT and Diabetes
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ScienceDaily looks at another line of research that may lead to effective therapies for type 2 diabetes: "Certain immune-suppressing drugs [greatly] increase the risk of developing diabetes. These drugs are known to put a stranglehold on a protein called calcineurin. ... mice that had been bred to produce calcineurin in the pancreas only until they were born, which had been born with a normal number of beta cells, were severely diabetic ... [scientists] used further genetic trickery to bypass calcineurin by artificially activating its protein sidekick, called NFAT. Beta cells lacking calcineurin but with active NFAT behaved normally, multiplying as the mice aged and producing normal amounts of insulin. ... Drugs that enhance the activity of calcineurin or NFAT could become a new treatment for type-2, or adult-onset diabetes, in which the beta cells don't produce enough insulin." Remember that type 2 diabetes is a lifestyle disease; most people can choose to avoid it, reduce its effects, or greatly postpone onset.

Link: http://www.sciencedaily.com/releases/2006/09/060920193541.htm

Alteon, Alagebrium, ALT-711
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Alagebrium - or ALT-711 - is one of the better known compounds discovered and developed with the intent of repairing a type of accumulated damage that leads to age-related degeneration. In this case, the damage is the buildup of extracellular protein crosslinks, and amongst them the type known as advanced glycation endproducts. Aubrey de Grey gives a good explanation of this topic and the level of interest one should have in ALT-711 at the SENS website:

Luckily, it happens that a lot of the cross-links that accumulate in this way have very unusual chemical structures, not found in proteins or other molecules that the body makes on purpose. This means that it is theoretically possible to identify chemicals that can react with the cross-links and break them, without reacting with anything that we don't want to break. And indeed, several years ago a group of chemists found such a molecule, which has now been tested in many different animals and also in humans and seems to lower blood pressure quite substantially. These chemists formed a company (named Alteon) to market the drug (named ALT-711), but it is still in clinical trials.

We need more work in this area. There are plenty of other types of cross-link that ALT-711 doesn't break, so we need other chemicals that will complement what ALT-711 does.

Another good introduction, with an emphasis on development for use as treatment for specific age-related conditions, can be found at the Alteon website:

Alagebrium is the only A.G.E. Crosslink Breaker in advanced human testing. The compound has demonstrated promising results in several Phase 2 human clinical trials and is being developed initially for cardiovascular and vascular diseases. Results to date suggest that alagebrium may be a novel therapy for a number of conditions that occur as a result of myocardial or vascular alterations associated with aging or diabetes. Preliminary evidence suggests that the compound is able to modify both the structure and function of the left ventricle (main pumping chamber of the heart) consistent with a partial reversal of pathology. Similarly, alagebrium has been shown to improve the reactivity and function of the arterial system. In addition, in all clinical testing to date, the compound has demonstrated a clean safety profile.

Alteon has gone through many of the reshapings common to young pharmaceutical development companies; the latest would seem to place them more in line for financial viability - and thus continuing development of ALT-711 for modest goals relating to the treatment of specific conditions. This is the sort of profile that maximizes the chance of attracting funding and clearing sufficient regulatory hurdles to make it to profitability.

The new management of Alteon Inc. (Amex: ALT), to further validate the Company's newly focused development of alagebrium on diastolic heart failure, highlights the recent publication of several articles that illustrate the medical community's increasing recognition of this form of heart failure. "A strong body of preclinical and clinical evidence supports our advancement of alagebrium's clinical development in diastolic heart failure," said Malcolm MacNab, M.D., Ph.D., Vice President, Clinical Development of Alteon. "The recent focus on this patient population by key opinion leaders further encourages our aggressive pursuit of this disease characterized by an unmet medical need."

It is unfortunate that the modern wasteful, useless regulatory burden so narrows and slows all medical development - but this is the inevitable consequence of overbearing, invasive government. When government employees dictact whether your business is permitted to succeed, venture funding will only be obtained by those who demonstrate the greatest ability to please government employees. Merits and goals are demoted to secondary concerns, and we all know where that leads.

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

Back to the alagebrium. My attention was drawn to a recent study suggesting that ALT-711 might have merit in the treatment of progressive kidney failure in diabetes, or diabetic nephropathy. There's an Alteon press release out there also, for those who don't enjoy reading scientific abstracts.

The renal morphological parameters characteristic of [diabetic nephropathy] decreased in treated compared with untreated mice. Conclusion: Alagebrium may prevent, delay, and/or reverse established [diabetic nephropathy] in db/db mice by reducing the systemic advanced glycation end product pools and facilitating the urinary excretion of advanced glycation end products.

This sort of investigation is fairly standard practice. Because it is so enormously hard to gain government approval for any compound, it makes economic sense to test it for other uses once you have or are close to having approval. Once again, regulation becomes the primary motivator for the practice of science and research, rather than efficiency, speed, merits and goals.

One might view Alteon and the development of ALT-711 as something of a transition from the old to the new in the community of folk seeking to extend the healthy human life span. It has its roots in the old school drug development pipeline and firm focus on supplements and things you can put in a pill. The aims, however, are well within the Strategies for Engineered Negligible Senescence (SENS), in that Alteon's founders and employees seek to effectively and deliberately repair a small portion of the cellular damage that cause age-related degeneration.

Early SENS research presently funded by the Methuselah Foundation and generous donors takes a somewhat different approach to the problem. Rather than drug discovery, they are working on bioremediation and bacterial enzyme discovery:

So how is LysoSENS supposed to work? In brief, we are looking for enzymes capable of selectively degrading the respective target material in the environment. This idea is heavily inspired by the field of environmental bioremediation (using microbes to degrade environmental contaminants). We are working in the lab of Bruce Rittmann, a well-known environmental engineer, as he has the expertise to find microbes that degrade weird stuff. We hope that we can isolate enzymes from these microbes and deliver them in a manner similar to current FDA-approved treatments for heritable lysosome storage diseases, where the missing enzyme is tagged with certain sugars for targeting and then injected into the bloodstrem. You can learn more about the LysoSENS strategy from its originator and Methuselah Foundation chairperson Aubrey de Grey here (quick and easy) or here (detailed and technical).

May the best science win, to the benefit of all.

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But Money Is What It Will Take
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While the results of any individual survey on attitudes to healthy life extension should be probably be taken with an appropriate amount of salt, trends over time in many surveys are interesting to watch. The Methuselah Foundation folk pointed me to a recent British survey:

Many Britons would give up favourite things, including sex, to reach 100 years of age, a poll suggests. Some 40% said they would give up sex - half of women and a third of men - 39% food and drinks and 42% travel.

But the Bupa survey of 1,003 people found 94% would not give up the company of family and friends and three quarters would not sacrifice money.

People cited being there for family and seeing grandchildren grow up as the main reasons for wanting to reach 100.

The poll, carried out by Mori for Bupa, also revealed half thought scientists should continue to keep trying to prolong people's lifespans, while 45% thought it was everyone's duty to live as long as possible.

But what if you didn't have to give up anything except money? That is the reality of matters today: we stand within sight of ways to greatly extend the healthy human life span, to live longer in vigor and youth, but the resources to get there are not yet dedicated to the task.

Today - and this is a large and important change from a decade ago - there are easy ways for ordinary folk to band together and devote individually modest amounts to help forge the future of longevity research. The Methuselah Foundation provides one such way: donating to the MPrize research prize or funding SENS research.

The future is what you make of it, both as an individual and in collaboration with others. Just as we prepare for retirement by looking ahead for decades and saving now, we can also help to make our later lives far longer, healthier and more youthful. The process is the same: we invest money now to make our future better, and the sooner you invest, the larger the eventual benefit. Scientists stand waiting for our support and encouragement - when we all step up to give material support to healthy life extension research, progress towards longer, healthier lives will greatly accelerate.

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Don't Call It "Old Age"
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Good points made via the Life Extension Foundation News: "The concept of 'old age' doesn't have much use when you're trying to get well. Almost all aches and ailments can be traced back to pathology - something that has gone wrong with the body, a disease. Once we have identified a disease, we know where we stand, and frequently we can offer a treatment. So attributing a problem to 'old age' doesn't help us solve it. But when we try to understand certain situations, particularly where an aged person is very ill, the idea of 'old age' starts to have some value. There is a feature of aging that we cannot attribute to a single pathology, and that feature is a buildup of multiple pathologies that won't get better, and which tend to worsen each other." There's no such thing as normal age-related degeneration; none of it should be normal, and we can effectively work towards addressing the root causes of all of it.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=4357

More Autophagy and Aging Research
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Ouroboros follows up on some of the more interesting recent research into the links between autophagy and age-related degeneration: "An old proverb has it that what is not growing is dying. Recent findings regarding autophagy - a process by which cells turn over old proteins and clear cellular detritus - lead me to believe that what is not self-degrading is also dying. A while back, we discussed a review that summarized the slowing of autophagy with increasing age. The efficiency of turnover decreases as an animal grows older, potentially creating a garbage catastrophe as increasing levels of damaged macromolecules further gum up the works. The upcoming issue of Molecular Aspects of Medicine has three reviews that treat various aspects of autophagy and aging in greater depth."

Link: http://ouroboros.wordpress.com/2006/09/22/on-the-benefits-of-eating-oneself/

Regenerative Research
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Wired takes a high-level look at present lines of research aimed at giving humans the regenerative capabilities of lower animals. The latter part of the piece also looks at the intriguing MRL mice, equipped with mighty regenerative capacities for a species of mammal: "[Heber-Katz] and her colleagues wanted to find out if other parts of these mice, known as the MRL strain, would also regenerate. So they performed some tests: They snipped off the tip of a tail, severed a spinal cord, injured the optic nerve and damaged various internal organs. All of the injuries healed, even the severed spinal cord. The results caused Heber-Katz to shift her research from autoimmune disease to regenerative medicine. Now, thanks to Darpa's call for grant applications in regeneration, scientists all over the country from various disciplines are working together on the MRL mouse."

Link: http://www.wired.com/news/technology/medtech/0,71817-1.html

Help Meet Peter Thiel's $3 Million Matching Grant For SENS Research
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We are fortunate to live in a era in which it is plausible to see significant progress towards far longer healthier lives within our lifetimes. Removing pain and suffering from old age - and pushing old age itself farther into the future - is now a reasonable goal for the vast, dynamic biotechnology and medical research infrastructures. All large goals require significant funding and public support, however. Serious research into the defeat of age-related degeneration is still in its infancy, supported by comparatively small groups and modest funding.

This state of affairs must change, and we are well on our way to making that change happen! Over the past two and a half years, ordinary folk like you and I have joined together in support of more and better research into increasing the healthy human life span. We have pledged more than $3.5 million to the Methuselah Foundation in this short time to (a) create the MPrize to encourage scientists to strike at the root causes of aging, and (b) fund the development of medical technologies to first treat and later eliminate age-related frailty, disease and suffering.

In September 2006, entrepreneur and investor Peter Thiel greatly advanced this cause with a $3 million dollar matching grant for donations to SENS research aimed squarely at the defeat of aging. For every $2 donated to the Methuselah Foundation's SENS research projects, $1 of this grant will be applied. We have until the end of 2009 to to exhaust this grant - so let's get to work!

The Strategies for Engineered Negligible Senescence (SENS), championed by biomedical gerontologist Aubrey de Grey, is perhaps the most important aging research taking place today. This is not because of present results, but because of its approach, influence upon other researchers and eventual payoff. SENS is a direct, efficient, fast-as-possible approach towards solving the problem of age-related degeneration:

SENS is a detailed plan for curing human aging. SENS is an engineering project, recognising that aging is a medical condition and that medicine is a branch of engineering. Aging is a set of progressive changes in body composition, at the molecular and cellular level, which are side-effects of essential metabolic processes. Many of these changes are eventually bad for us -- they are an accumulation of damage, which becomes pathogenic above a certain threshold of abundance.

The traditional gerontological approach to life extension is to try to slow down this accumulation of damage. This is a misguided strategy, firstly because it requires us to improve biological processes that we do not adequately understand, and secondly because it can even in principle only retard aging rather than reverse it. An even more short-termist alternative is the geriatric approach, which is to try to stave off pathology in the face of accumulating damage; this is a losing battle because the continuing accumulation of damage makes pathology more and more inescapable.

Instead, the engineering (SENS) strategy is not to interfere with metabolism per se, but to repair or obviate the accumulating damage and thereby indefinitely postpone the age at which it reaches pathogenic levels.

SENS research projects have been funded by the Methuselah Foundation since late 2005, and continue to grow as support for the Methuselah Foundation increases.

Now is the best of times to invest in your future health and longevity. By supporting the Methuselah Foundation, your donation will help to develop the scientific foundation for medical technologies to improve health and longevity for all. Now your donations will stretch even further: for every $2 you donate to support new SENS research, Peter Thiel will donate an additional $1 from his matching fund.

The future of our lives is not some remote line item in the hands of distant scientists: we are all responsible for building our future. You, I and everyone else can make a real difference to our healthy longevity and the science that will ensure it. What are you waiting for?

$300,000 Newly Pledged to the MPrize
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(From the Methuselah Foundation Blog). Three new members of The Three Hundred have pledged their support to the Methuselah Foundation and longevity research since Peter Thiel's $3.5M donation was announced. The latest Three Hundred member has pledged $250,000! He says: "Over the course of all human events, there never has been any time so dynamic, vibrant and exciting as today. What a wonderful time to be alive. Because of accelerating advances, being alive today is becoming second only to being alive tomorrow. Accelerating scientific advances in understanding are enabling ever increasing, extraordinary technologic innovations. Rocketing us into a future of enormous promise. The future, is indeed, quite bright." Thiel's $3 million matching grant applies to the ongoing donations of all Three Hundred members who choose to help fund SENS research conducted by the Methuselah Foundation - today is a good day to join!

Link: http://blog.methuselahfoundation.org/2006/09/welcome_to_the_latest_members.html

Halting Alzheimer's In Rats
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EurkeAlert! looks at progress in halting the progression of an animal model of Alzheimer's disease: "Stimulation of a receptor in the brain that controls insulin responses has been shown to halt or diminish the neurodegeneration of Alzheimer's disease ... peroxisome-proliferator activated receptor (PPAR) agonists prevent several components of neurodegeneration and preserve learning and memory in rats with induced Alzheimer's disease (AD). ... This raises the possibility that you can treat patients with mild cognitive impairment who have possible or probable Alzheimer's disease." This follows on from previous work in which "the researchers demonstrated that Alzheimer's is a brain-specific neuroendocrine disorder, or a Type 3 diabetes, distinct from other types of diabetes." Lo and behold: benefits from a class of compound already in use for type 2 diabetes. Do more readily available anti-diabetes strategies also hold off Alzheimer's? Time, and further research, will tell.

Link: http://www.eurekalert.org/pub_releases/2006-09/l-irs092106.php

The Wrestling of Knee-Jerk Reactions in the Minds of the Many
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People don't spend much time evaluating new information that crosses their path. That's simple economics; you have to filter the world in a way that is efficient if you are to have any time left to set and meet your own goals. Modern attempts to build reputation systems are partially an effort - possibly doomed, depending on who you ask - to do better than the ad hoc personal filters built and used by most people.

It is fascinating to watch large numbers of individual filters interacting in action, and recent events have provided a good laboratory. Peter Thiel, an individual of high reputation in many eyes, has donated $3.5 million to the Methuselah Foundation to fund real, honest to goodness scientific anti-aging research, a field that has a terrible reputation in the eyes of many. This is poor reputation for legitimate science is due in no small part to the fraud, greed and idiocy of the "anti-aging" marketplace, but also to the knee-jerk negative reaction that so many people have to the very idea of working to extend the healthy human life span.

This is an interesting experiment: find any random person you know and ask them what the downside would be to using better medicine to live for 150 years. Nine times out of ten, I'll wager, your friend will tell you that living for so long would be terrible because a person would spend most of his or her life decrepit, increasingly crippled by age-related conditions. In otherwords, your random friend thinks that "healthy life extension" means "being aged for longer."

So here we have a war of first-line, knee-jerk filters based on reputation, prejudice and habit. Does Thiel's association with scientific anti-aging research cause people to put Thiel into the "reject" category at this filter level, or does it cause people to pass the idea of scientists working to extend the healthy human life span through to the next level of inspection, thought and discussion?

From my admittedly scant view of the online world, I'm gratified to see that Thiel's perceived reputation is winning more often than one might expect. In many ways, Thiel's reputation and standing are a more potent donation to the Methuselah Foundation - and the Strategies for Engineered Negligible Senescence (SENS) - than the $3.5 million. It will go a long, long way towards legitimizing the fight to defeat aging - and frailty, suffering, pain and death - in the minds of the many.

Still, it is a sign of the power and breadth of shallow prejudice against healthy life extension that a fair number of people are willing to instantly dismiss to the crank bucket someone previously regarded as an intelligent, successful, talented businessman. There is much work left to do for advocates attempting to create broader awareness and education, as well as those researchers who are proving their case in the labs.

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The Edmonton Aging Symposium
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The tireless Kevin Perrott, executive director of the MPrize competition, is presently organizing the Edmonton Aging Symposium for March of 2007. As the growing program shows, Perrott is making good progress in attracting speakers of note. "This symposium is designed to bring an awareness of the rapid pace of the development of intervention-oriented therapies in age-related dysfunction to the non-scientist and the lab-hardened researcher alike, as well as draw the attention of policy-makers to the massive economic benefits available to those who create an environment where these technologies can be developed and implemented at all possible speed. ... The science-oriented sessions focus on the types of damage that accumulate with age, both what is known or can be done at present to slow or repair them, and what we might see in terms of future therapies."

Link: http://www.edmontonagingsymposium.com/

Stem Cells, Managed Expectations
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The successes of first generation stem cell therapies must be matched against the failures - there is no shortage of failure in any new and dynamic field. Understanding how to best use stem cells to induce regeneration is an ongoing process, and our expectations of progress must be kept realistic. From Forbes: "Two German trials that used injected stem cells to strengthen the heart muscle after a heart attack got good results, while a small Norwegian trial showed no benefit. All three trials used stem cells derived from bone marrow. ... The injection fraction of the stem-cell recipients improved by 5.5 percent, compared to 3 percent for those who got conventional treatment ... After a year, the stem-cell recipients had a significantly lower incidence of second heart attacks. Their death rate was lower and fewer of them needed treatment to reopen blocked blood vessels. ... In sharp contrast, the Norwegian [study] showed no beneficial effect."

Link: http://www.forbes.com/forbeslife/health/feeds/hscout/2006/09/20/hscout535032.html

Embryonic Stem Cells Versus Blindness
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Washington Post reports on new embryonic stem cell research from Advanced Cell Technology: scientists "started by developing a reliable method for turning embryonic stem cells into retinal pigment epithelium cells, which nourish the light-sensitive 'photoreceptor' cells in the eye. In macular degeneration, the pigment cells gradually disappear. The researchers achieved the transformation in all 18 stem cell lines they worked with ... treated rats had twice the visual acuity of the untreated rats nearly three months after treatment." Like much of ACT's present work, this is an early stage technology demonstration. It shows an increasingly sophisticated level of control over stem cell differentiation and examples of newly developed tools, processes and infrastructure needed to get the job done.

Link: http://www.washingtonpost.com/wp-dyn/content/article/2006/09/20/AR2006092001674.html

Changing Human Life Span Means Changing Human Society - For the Better
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I received a characteristically interesting email from James Clements just recently, and thought it well worth sharing. The links are mostly added by my hand as a part of an ill-formed habit of annotating the work of others via HTML:

About 20 years ago, I read Durk Pearson and Sandy Shaw's Life Extension Handbook. It was a revelation to me that scientific advances might, in my lifetime, allow us to live hundreds of years. One of the first things I thought of (having matured during the Vietnam War protests, Civil Rights, and Watergate) was that if we could change the average human lifespan from 70-80 years to 700-800 years we would likely change Society for the better in at least the following ways:

1) The Environment. Who would want to ruin the environment and rape and pillage the land if they had to continue living here for so long?

2) Education. The longer one lives the more easily they can improve their minds through cumulative education. Instead of cramming learning into an 8-16 year period, it would likely be spread out with intervening work over decades. Who would want to work all their life at menial labor if they knew that they could go back to school, improve their mind and pick up new skills, and then have decades or centuries to practice their new trade? Why wouldn't this process just keep repeating over and over?

3) War. There's a reason why the disposable members of the Army are primarily made up of 18-22 year olds - they do not fear death as much and if they think about old age, they think that dying young might be preferable to growing old and decrepit. But, who would want to die young fighting in wars when their lifespan could otherwise be hundreds of years? I truly believe that LIFE will become more precious, not less, when the vast majority of people live hundreds of years. Also, you see it around the world; mostly countries that have a preponderance of young people in their population go to war.

Countries are much less likely to go to war, have civil wars, or high crime rates the older their median population is: http://www.edwardhugh.net/medianage.html. There are 25 countries in the world today whose median ages are LESS THAN 18 year old! And, when you look at this list, they are poor, violence ridden countries full of young people who have no hope and nothing to lose.

Upon consideration of the matter for a number of years, my attitude has not changed. I believe that Mankind would radically change for the better if our lifespans increased significantly. We would likely not reach any kind of Utopian state anytime in the foreseeable future, but we could certainly be a much kinder, gentler, and more prosperous place.

What we're doing will change Human history for the better.

The time preference imposed upon us by the present span of our lives determines the shape of our society.

Time preference is the economist's assumption that a consumer will place a premium on enjoyment nearer in time over more remote enjoyment. A high time preference means a person wants to spend their money now and not save it, whereas a low time preference means a person might want to save their money as well.

A future we will not live to experience has less value to us, so we feel more able to despoil it in any number of ways - the victory of short-term gratification over greater long-term gain. If you look back in history to ages of much shorter, disease-ridden lives, the actions of the time often seem as though the world was populated solely by madmen and the drunk - but in large part, this shape of history was formed by the short time preferences of those who lived it.

To expect to be alive, healthy and in your 40s is a luxury that all to many of the people who ever lived did not have. But most people today have no expectation of being alive, healthy and 100 - the actions, choices and contributions that form society reflect this view of the future. What if you could expect to see a healthy 150th or 200th year? Or live all the way to 800 in good health, for that matter. How then would you prioritize and act in your life? Quite differently than you do today, most likely.

We have a fighting chance at engineering our way to actuarial escape velocity - the point at which medical science increases healthy life span faster than we age - within our lifetimes. To seize this chance, we must gain the support of tens of millions of earnest folk and raise a mighty research infrastructure to rival the cancer establishment in size, dedication and scope. This can be done - it has been accomplished in past decades for cancer, AIDS, Alzheimer's, diabetes and other conditions.

We can do this for aging, and thereby change the world for the better.

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Bone Scaffold From Bacteria
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An interesting article surfaced in the Daily Beacon on the use of bacteria to build scaffold material for transplant and bone regeneration. "Hutchens's idea for using bacterial cellulose to replicate bone began four years ago ... These bacteria are like spiders that swim around and weave this pure cellulose into a mesh ... We just lift off that layer, clean it, and then we are ready to use it. It is similar to tissue ... Comparing her synthetic calcium-phosphate material to actual bone, Hutchens found that the nanostructure was very similar. ... Whether this bioengineered bone will grow in the body is unknown, but that is the UTK student's next research step. Hutchens is preparing the paperwork required to conduct a biological study where she will implant her bone-like gel into an animal model. That test will determine whether the bone gel can attract developing bone cells, or osteoblasts, to an injured area and elicit bone regeneration." Past studies show that the right sort of scaffold material makes all the difference in enhancing regeneration in the body.

Link: http://dailybeacon.utk.edu/showarticle.php?articleid=50495

Transplants Made to Order
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The Scientist takes a conservative look at the present grail of tissue engineering: "The possibility that we might engineer replacements for worn out tissues - from the simple slips of cartilage that cushion joints to fully differentiated, functional grafts in a ready-to-use format - is increasingly plausible. ... While visions of a healthy, shrink-wrapped heart ready to drop in the chest cavity of a needy patient are pure fantasy for now, tissue engineering is remarkably close to producing biological grafts that can reestablish normal tissue structure and function across different size scales, on a long term, and with the ability to remodel in response to environmental factors, growth, and aging."

Link: http://www.the-scientist.com/article/home/24539/

From Around the Web on Thiel's $3.5 Million Donation
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Today, I thought I'd direct your attention to a selection of comments and thoughts from around the web on Peter Thiel's $3.5 million vote of confidence for the Strategies for Engineered Negligible Senescence (SENS) and the Methuselah Foundation. Starting with the more mainstream side of the house:

R&D into eternal life doesn't come cheap

If you're going to live forever, then you'll probably need to set aside a little something extra in that retirement account.

And if you're doing research into getting people to live forever--or at least well beyond their three score and ten--then you'll probably need some up-front cash. To that end, PayPal co-founder Peter Thiel has ponied up a $3.5 million gift for scientific research into aging and its ravages. But the scientist receiving the gift wants to do a little more then fight wrinkles--he's hoping to "cure" aging itself, letting humans live for a thousand years.

The Methuselah Foundation, a Springfield, Va, organization run by Aubrey de Grey, sounds like something out of a Robert Heinlein novel.

Entrepreneur backs research on anti-aging Scientist says humans could live indefinitely

De Grey told The Chronicle in e-mails and phone conversations last week that he isn't disturbed by scientific critics. Some of them, he noted, argue that death is inevitable because the cells and genes of living organisms inevitably accumulate errors that eventually kill them. But, he pointed out, because of careful upkeep "we have vintage cars driving around that were designed to last 15 years -- and they're 100 years old."

So why should humans be any different?

De Grey, who received a doctorate in biology at Cambridge University in 2000 and worked in the university's genetics department from 1992 until a few months ago, characterized the $3.5 million grant as a "major breakthrough" in his effort to get research on indefinite extension of life span "really moving in the laboratory."

"It's "pump-priming," he said. "I need probably $1 billion over 10 years" to achieve that goal."

Forever Young? The 5000 year lifespan

The promise of extra years of life is an attractive one.It would mean more time to spend with friends, to enjoy life and better get to know oneself. What do you think? How far can we extend our lifespans?

Not that the Australian commenters think much of the idea of healthy life extension in that last link above. Still, it will be increasingly hard to hold up skeptical ignorance as a shield in the years ahead. Once the science funding starts rolling - and real results appear and are confirmed - advocacy and education will really take off. Folk like me will be off in planned obsolescence as the real, practiced patient advocacy groups take over - and do a far better job of it too, no doubt.

Moving on now to the much more eclectic, interesting and generally opinionated blogosphere: you'll want to click through to this first post from Michael Anissimov for some photographs of the formal acceptance of the $3.5 million donation.

Accelerating Future:

I was fortunate to meet with Aubrey when he was in San Francisco to formally accept Thiel's gift, talking with reporters and filming a promotional video. Aubrey attended a meeting of BA-Trans that I organized. Other attendees were Bruce Klein and Susan Fonseca-Klein, who were original founders of the Immortality Institute, and Adam Kamil, a frequent poster on ImmInst who flew in from LA to be at this event.

Paul Boutin:

To my surprise, Aubrey was fond enough of my Slate piece on him last year that he invited me to the signing at Thiel's home a short hike from mine in San Francisco. Another attendee shot some video of the event that may be on YouTube soon. I asked Peter why he was funding this particular organization. To paraphrase, he feels the Methuselah Foundation is pushing an area of research that's been neglected as investors and scientists chase more lucrative short-term projects to cure aging's effects - Alzheimer's, cancer, heart disease, etc - rather than to find its root causes. His verbatim quote for a press release: "I'm backing Dr. de Grey, because I believe that his revolutionary approach to aging research will accelerate this process, allowing many people alive today to enjoy radically longer and healthier lives for themselves and their loved ones."

FuturePundit:

I expect Thiel's donations to be the first of many very large donations aimed at reversing the aging process. The large number of multi-millionaires are very sharp people who know they really can't take their money with them when they die. So why not use a piece of their wealth to take a stab at making their bodies young again?

The full reversal of the aging process is an achievable goal. We will develop the biotechnologies to grow replacement parts, to do gene therapy, to send in stem cells to do repairs, and to remove the junk that accumulates in cells and between cells as we age. Daily announcements from biological resesarch labs demonstrate progress toward many of the technologies needed to reverse the aging process. Some people who are alive today will live to see the conquest of aging and the end of death from old age.

Instapundit:

Bring it on.

Metamagician and the Hellfire Club:

Three cheers for Aubrey!

Now, I'm not at all qualified to comment on the soundness of de Grey's theoretical work, but if private money is being put up to test it, then that's a great step forward from my particular viewpoint. I'd welcome some public money going into the enterprise as well, though for now there's an argument for prioritising it to more mainstream anti-ageing research, such as that of S. Jay Olshansky and his colleagues.

Digital Crusader:

This money is especially important because it represents the *start* of building up our research infrastructure.

Cameron's Brain:

Very exciting to see more entrepreneurs getting behind life extension research. If Gates and Buffett threw some of their Gigantor cash at it, it could probably get knocked over in ten or twenty years.

Better than how other high-tech billionaires have spent their money:

the effort to accumulate and hoard these vast claims on the resources of our society seems pointless to me. Super-wealth won't do you any good in the long run if can't buy you more than the average life expectancy in developed countries. Considering that all the "supercentenarians" I've heard of never had that much in the way of money, and we can't yet buy ourselves their better genes, it looks like the super-wealthy don't have much to look forward to until they can pay someone like Aubrey de Grey to invent and engineer repairs to our aging-susceptible biochemistry.

I have to echo that last point. There is no point to wealth at any level if you cannot use it to buy the only currency that truly matters - more healthy life.

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Yet More Nanofiber-Enhanced Healing
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The Chemical & Engineering News notes another group working on enhanced healing via nanofibers: researchers "combined neural stem cells [with] carbon nanofibers and injected the cocktail into damaged regions of the brains of rats that had suffered a simulated stroke. After a few weeks, [nanofibers] with stem cells promoted the growth of new neural tissue. On their own, neither nanofibers nor stem cells triggered neural tissue regeneration. Webster attributes the mixture's regenerative power to the fibers' favorable interaction with laminin, a key protein for promoting stem cell differentiation into neurons. Webster also thinks the nanofibers' ability to conduct electricity could help wire the neurons to one another." We are in the early days of discoverying practical methods for controlling and guiding the work of stem cells; present limited therapies will only get better with time.

Link: http://pubs.acs.org/cen/news/84/i38/8438nanofibers.html

Peter Thiel Gives Us All a $6 Million Challenge
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As I'm sure you folk have already noted, the multitalented and quite wealthy Peter Thiel has stepped up to make a difference to the course of serious anti-aging research:

Mr. Thiel will donate a total of $500,000 over the next three years to fund pilot research projects intended to deliver early stage validation of the "SENS" approach to combating the debilitation caused by aging.

Additionally, from now until the end of 2009, Mr. Thiel promises to match every Dollar donated to the Methuselah Foundation for SENS research with a 50 cent matching contribution from himself, up to a maximum of $3 Million of matching funds.

All good investments align and reinforce interests and incentives on both sides. The Methuselah Foundation has made great progress since its launch in 2003, but now the Foundation, its volunteers, donors and supports must prove they can grow into the big leagues. The Foundation has raised more than $3.5 million in pledges in the past couple of years, for both initially modest research and the MPrize to inspire others to follow suit, but much more funding is needed as a lever with which to move the world. We want to see a cure for aging, and meaningful therapies for the root causes of aging rapidly enough to help those reading this now. Ambitious goals require ambitious resource allocation.

Thiel has given us, all of us, a worthy challenge: raise $6 million in 3 years for Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS) research and he will match that with a further $3 million. That level of funding would place SENS research on a par with the new Paul F. Glenn Laboratories for the Biological Mechanisms of Aging. in other words, an organization capable of shaping the application of billions of dollars of medical research funding - and the opinions and work of tens of thousands of the most important scientists in relevant fields - in the years ahead simply by the merits of its existence.

The challenge to raise funding is a proxy for the challenge to prove your cause worthy and likely to succeed. To raise $6 million from the philanthropic community, you need compelling science that stands up to peer review, widespread support, a strong message, and the organizational success gene - the people who build a community to make it work.

With that in mind, I think we all should take a moment to congratulate the energetic and dedicated volunteers of the Methuselah Foundation. These folk have shaped and guided this vehicle all the way its present success - at their own expense, and giving time and effort far beyond the call of duty. I'd be out here plugging away and on message, Methuselah Foundation or no Methuselah Foundation, but the folk behind the scenes have given a great deal more expertise and time than I. Congratulations all, and thank you for making this work.

All who have donated to the Foundation have helped to create a organization that is now successfully penetrating the philanthropist demographic and raising seven-figure sums.

Resources for research must come from somewhere if we are to escape our fate of suffering and death by aging. We must explain our goal; educate the public; raise widespread support; motivate the scientific community. We have made good, strong progress in the past few years - but a long road lies ahead. As a community, we have yet to successfully engage and persuade the wealthiest and most conservative of philanthropists, seeking support for modern, aggressive bioengineering approaches to the problem of age-related degeneration.

We can do this. We must do this. Too many lives, too much suffering is at stake to fail.

We should all be proud of ourselves - briefly, and then turn to the challenge ahead. Thiel is well-respected as a shrewd investor in the venture funding and philanthropic communities, and that he stands openly in support of the Methuselah Foundation will open many doors. We can all help the Foundation rise to the $6 million fundraising challenge by spreading the word far and wide - and by continuing to show that funding by serious anti-aging research has widespread grassroots support.

Donate to fund SENS research today and Peter Thiel's dollars stand beside yours in support of far longer, healthier lives for all. That's a chance not to miss!

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$3.5M For the Methuselah Foundation
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The Methuselah Foundation has received its second seven-figure donation: $3.5 million from Peter Thiel. "Rapid advances in biological science foretell of a treasure trove of discoveries this century, including dramatically improved health and longevity for all. I'm backing Dr. de Grey, because I believe that his revolutionary approach to aging research will accelerate this process, allowing many people alive today to enjoy radically longer and healthier lives for themselves and their loved ones. ... Mr. Thiel will donate a total of $500,000 over the next three years to fund pilot research projects intended to deliver early stage validation of the 'SENS' approach to combating the debilitation caused by aging." Most of this money comes as a $3 million matching grant intended to speed further significant fundraising for research. There has never been a better time to donate to the Methuselah Foundation to help fund the new Strategies for Engineered Negligible Senescence (SENS) research projects!

Link: http://www.mprize.org/index.php?pagename=newsdetaildisplay&ID=0107

Reducing Future Existential Risks Versus First Things First
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At the tail end of an Accelerating Future post on just how easy it will be to cause mayhem with a future molecular manufacturing technology base to hand, you'll find this:

Life extensionists: realize that the greatest risk to living longer is not actually aging, which we will eventually defeat cleanly, but existential risks of the type I frequently discuss, including superintelligence and nanotech arms races. You can extend your expected future life more by lowering the probability of these disasters than through any other means.

I think this falls well inside the "too damn optimistic" zone. We - even the younger ones amongst us - won't make it to the stage of being unthreatened by age-related suffering, disability and death unless an all-out effort to tackle the root causes of aging begins soon. We're getting somewhere at some pace today, but it's a trickle that needs to be a flood:

I'd be optimistic myself if a scientific healthy life extension infrastructure as dedicated, large and advanced as that for cancer or Alzheimer's research actually existed. But it doesn't, and the scientific and advocacy communities have barely even started on the long road to building such a thing. The process could have been started a generation ago, but it wasn't. It may not get off the ground this generation.

First things first is what I say to discussions of this ilk. There is a generation of healthy life extension technology to be developed before the very earliest commercial molecular manufacturing arrives. There is a generation of groundwork to be done so as to take advantage of advanced nanotechnology for longevity medicine. None of this is happening today in any sort of volume; even the lengthy process of creating the necessary infrastructure is not yet meaningfully underway. We need to set out and change this sorry state of affairs if any of us are to have the luxury of focusing exclusively on the new existential risks of decades ahead.

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Macroautophagy and Aging
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From PubMed, a look at the role of autophagy in aging: "Macroautophagy is a process that sequesters and degrades organelles and macromolecular constituents of cytoplasm for cellular restructuring and repair, and as a source of nutrients for metabolic use in early starvation. Extensive evidence has been reported that macroautophagy process declines with increasing age. This impairment, probably due to ad libitum feeding, may cause accumulation of altered structures leading to the age-related decline in cell functions. It has been suggested that caloric restriction (CR) and disruption of insulin-like signals contrast the process of aging by prolonged stimulation of macroautophagy. According to this hypothesis, it is shown that life-long weekly administration of an anti-lipolytic drug decreases glucose and insulin levels, stimulates autophagy and intensifies anti-aging effects of submaximal CR." To summarize: more rather than less autophagy is most likely good for your health; calorie restriction - demonstrated to be good for your health - inspires more autophagy; the future use of drugs to same end is plausible.

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16973209

The Metabolic Stability Hypothesis
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A new hypothesis on aging via the Juvenon Health Journal: "In general, species with higher metabolic rates have the shortest life spans. Demetrius's hypothesis holds that it is not the stresses of life, such as oxidative stress produced by free radicals, or the relative metabolic rates, that are important in determining life span. He believes the more important issue is metabolic stability, which is defined as the capacity of the networks of cellular metabolic pathways to continue to run smoothly, even during times of stress. ... One established method to increase life span in the mouse is caloric restriction (CR). Of interest, and in support of this theory, is experimental evidence showing that caloric restriction does in fact tend to stabilize metabolic pathways." This leads to the conjecture that CR will not do much for human maximum longevity, even though it is demonstrably effective at lowering risk for age-related conditions, as a healthy human already has a much more stable metabolism than mice.

Link: http://www.juvenon.com/jhj/vol5no09.htm

Calorie Restriction, Glycolysis and Aging
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The folk of the Calorie Restriction Society mailing lists recently pointed out a couple of papers proposing yet another way in which calorie restriction (known as dietary restriction in some scientific circles) may slow one of the root causes of age-related degeneration.

Glycolysis is a near-universal metabolic processing of glucose, a part of the normal day to day operations of your cells. However, like most metabolic processes, it generates intermediary and other products that can - and do - cause damage to cellular machinery. In essence, cells can get gunked up with sugars and sugar by-products. The first paper from earlier this year sets the stage:

Does Chronic Glycolysis Accelerate Aging? Could This Explain How Dietary Restriction Works?

The mechanisms by which dietary restriction (DR) suppresses aging are not understood. Suppression of glycolysis by DR could contribute to controlling senescence. Many glycolytic intermediates can glycate proteins and other macromolecules. Methyglyoxal (MG), formed from dihydroxyacetone- and glyceraldehyde-3-phosphates, rapidly glycates proteins, damages mitochondria, and induces a prooxidant state to create a senescent-like condition. Ad libitum-fed and DR animals differ in mitochondrial activity and glycolytic flux rates. Persistent glycolysis in the unrestricted condition would increase the intracellular load of glycating agents (e.g., MG) and increase [reactive oxygen species] generation by inactive mitochondria. Occasional glycolysis during DR would decrease MG and reactive oxygen species (ROS) production and could be hormetic, inducing synthesis of glyoxalase-1 and anti-glycating agents (carnosine and polyamines).

Which is the longer and more precise way of suggesting that (a) calorie restriction may lead to a more efficient metabolic process that produces less sugared-up (glycated) gunk to damage the cell, and (b) having just a little sugared-up gunk might actually be better for you than having none, a phenomenon known as hormesis. For a high level overview as to why having glycated junk floating around in your cells - or damaged, ROS-generating mitochondria - contributes to aging, you might want to try the science section of the Strategies for Engineered Negligible Senescence (SENS) website.

A second and more recent paper from the same researcher digs a little deeper into these mechanisms, using the comparison in results between constant calorie restriction and strategies such as alternate day fasting.

Dietary restriction, glycolysis, hormesis and ageing

The possibility is discussed that dietary restriction modulates ageing and onset of related pathologies by, in addition to upregulation of proteolysis, suppression of glycolysis which in turn decreases generation of methylglyoxal (MG), a highly toxic glycating agent which can provoke cellular senescence and many age-related pathologies. This proposal is supported by the observation that intermittent feeding can mimic dietary restriction's effects on mouse lifespan without any overall reduction in calorie intake. That MG-induced modification of the chaperone and anti-apoptotic protein (Hsp27) increases its protective functions suggests a possible hormetic response to transient MG production during transient periods of glycolysis in dietary restricted animals. It is suggested that in the ad libitum-fed state permanent glycolysis would suppress proteolysis and continuously generate MG which overwhelms the anti-MG defence systems. It is proposed that periods of fasting might be a more acceptable approach than permanent undernutrition in our attempts to slow human ageing, although timing of meals may prove important.

Proteolysis is the catch-all name for ways in which the cell gets rid of the proteins it doesn't want, such as harmful glycated proteins produced as a side-effect of glycolysis.

It is interesting to see biochemical arguments being marshalled on the side of intermittant fasting; the final answer as to the best way to use calorie intake to tune your metabolism will come with a more complete understanding of the processes involved. While there is no such thing as useless biochemistry in the long run, calorie restriction research - implicitly aimed at slowing the accumulation of some types of damage that causes aging - seems to me to be somewhat less important than finding ways to repair that damage. Slowing damage only gets you a little further down the road of longevity; repairing damage means the ability to go as far as you care to.

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Xenotransplantation Versus Diabetes
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Medical News Today notes further progress towards the use of xenotransplantation to cure type 2 diabetes: "Unlike embryonic stem cells, which can become virtually any cell type, primordia are locked into becoming cells of a particular organ. Their approach for diabetes treatment uses pig pancreatic primordia. In previous research, they found that obtaining the primordia early in the pigs' development rendered them 'invisible' to the rats' immune system, eliminating the need for antirejection drugs. ... The transplanted primordia not only appropriately regulated blood sugar in the type 2 diabetic rats, they also reduced insulin resistance. The rats are cured by pig insulin, which comes from the transplants and can be measured in their circulation. The rats' own insulin-producing cells in the pancreas are atrophied." Remember that type 2 diabetes is a lifestyle disease: the majority of sufferers could have avoided it though better choices.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=51792

The Cost of Not Caring
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A look at the personal cost of not caring about your health from Medical News Today: "As many chronic diseases are closely linked to lifestyles, an estimated 80% of heart disease, stroke and type 2 diabetes, and 40% of cancer, could be avoided if common lifestyle risk factors were eliminated. ... Seven leading risk factors - high blood pressure, tobacco, alcohol, high cholesterol, overweight, low fruit and vegetable intake and physical inactivity - account for almost 60% of all ill health in [Europe]." Ignore the politics and the implicit assumption that change must be forced on people; take away the point that not taking care of your health has a large future cost: suffering, money and an early death. We all know that medical science is advancing, but why gamble your life and wallet on being rescued from the consequences of your own inaction? You can do better than that, and greatly increase your chances of living to see healthy life extension medicine that will extend your healthy life still further.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=52025

Everyone Can Help In Some Way
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The future of healthy life extension research and the scope of our potential longevity is not walled off and out of reach to folk like you and I. It is a matter very much in our hands, open for all of us to influence and change. We can all help to bring about a future of working rejuvenation medicine - technology that really can repair the fundamental damage that causes aging, not just paper over the cracks. Thoughts from Anne C.: "Let's be realistic: if healthy life extension is to be achieved in time for many of us currently alive to take advantage of it, people need to start taking action now, with available resources, not imaginary ones. That is, we can't afford to wait for certain tools to develop before making a start. Everyone can do something." The future is exactly what we make of it, working together - no more and no less. If we want longer, healthier lives, than we must set forth to make that medical technology a reality.

Link: http://rationallongevity.blogspot.com/2006/09/on-optimization.html

Overpopulation: Not a Problem Now, and Never Will Be
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A future of overpopulation is one of a number of hoary old objections to progress and longer, healthier lives. It has been raised over and over again throughout recent history, but like all other Malthusian concepts, it was wrong then, and it's just as wrong now. Common Malthusianism - the idea that a given resource (such as living space or food) will run out in the future based upon extrapolation of present trends - stems from fundamental misunderstandings about economics, human action and change. We create change in response to our environment; our self-interest leads us to constantly strive at the creation of new resources where old resources are becoming scarce and expensive. This is the path to profit for the individual - and progress for all. One needs a certain amount of willful blindness to avoid seeing the process in action now and in recent history.

The ideas of Malthus were just as wrong as the ideas of those who warn of overpopulation today, and for just the same reasons. The simple answers to any claim of overpopulation with increasing longevity are much as follows:

1) Population growth declines and reverses with increasing wealth, longevity and technological progress:

Decelerating population growth appears to be an inevitable result of growing wealth. Early on in a country's developmental curve, children can be regarded as 'producer goods' (as economists would say). Parents put their children to work on the farm to generate food and revenue. Very little effort is put into caring for the child: no expensive health plans, special classes, trips to Disneyland, X-Men action figures, or mounting phone bills. As we become wealthier, children become 'consumer goods'. That is, we look on them more and more as little people to be enjoyed and pampered and educated, not beasts of burden to help keep the family alive. We spend thousands of dollars on children to keep them healthy, entertain them, and educate them. We come to prefer fewer children to a vast mob of little ones. This preference seems to be reinforced by changing tastes resulting from improved education.

UPDATE 05/28/2010: Researchers Leonid Gavrilov and Natalia Gavrilova have produced detailed population models to demonstrate that even large increases in human life span produce comparatively small changes in population size. You can find a summary near the end of a more recent Fight Aging! post, or at PubMed:

For example, we applied the cohort-component method of population projections to 2005 Swedish population for several scenarios of life extension and a fertility schedule observed in 2005. Even for very long 100-year projection horizon, with the most radical life extension scenario (assuming no aging at all after age 60), the total population increases by 22% only (from 9.1 to 11.0 million). Moreover, if some members of society reject to use new anti-aging technologies for some religious or any other reasons (inconvenience, non-compliance, fear of side effects, costs, etc.), then the total population size may even decrease over time.

2) It is self-evident from even a few back of the envelope calculations that the Earth can support tens of billions in comfort using the technology of today - and never mind the rest of the solar system once the cost of getting into orbit has been sufficiently reduced.

So it turns out that if 5% of the United States were converted into urban area with a population density of 6,000/km2, and 45% were converted into suburban area with a population density of 2,000/km2, with the remaining 50% left for rural area, parks, and farms, there would be enough room for 3 billion in the urban areas, and 9 billion in the suburban areas, for a total population of 12 billion. This is in the US alone. This scheme could be extended to the other countries and continents for a total population of around 100 billion. Everything between the Arctic and Antarctic circles are potential targets for colonization. This is about 130,000,000 km2 of land area (the circumpolar regions have about 20,000,000 km2 of land).

3) What some presently view as "overpopulation" is more accurately described as crushing poverty amidst the potential for plenty and resources left unused. This is the result of despotism, corruption, economic ignorance, short-sighted greed and the inhumanity of man unto man - it is not a matter of counting heads.

Here, then, is a short guide for kleptocrats and egalitarians who want to keep their countries poor. All of these policies have stood the test of time as techniques for creating and maintaining poverty. The list is by no means exhaustive, but it will give would-be political leaders a good idea of how to start their countries on the road to ruin.

Malthusianism and cries of overpopulation in the face of a future of healthy life extension are forms of relinquishment. It is a call for death and suffering to continue on a massive scale; a certain type of person prefers any present horror to the uncertainty of change. Fortunately, such people have usually been swept aside in the past by the urge of the many to better their lives, one step at a time. May that long continue to be the case.

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CR and Alzheimer's Again
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Via EurekAlert!, more on calorie restriction (CR) and Alzheimer's disease (AD): "The present study strengthens the possibility that CR may exert beneficial effects on delaying the onset of AD-amyloid brain neuropathology in humans, similar to that observed in squirrel monkey and rodent models of AD ... The researchers found that ~30% calorie restriction resulted in reduced AD type amyloid neuropathology in the temporal cortex relative to control fed monkeys. The decreased AD type neuropathology correlated with increased longevity of related protein SIRT1, located in the same brain region that influences a variety of functions including aging related diseases." It seems that calorie restriction improves your prospects in all matters of aging examined to date.

Link: http://www.eurekalert.org/pub_releases/2006-09/tmsh-cri091506.php

Alzheimer's and Diabetes
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Links between Alzheimer's and diabetes continue to solidify. This JS Online piece takes a high level look at the present scientific consensus: "Insulin is the hormone that helps regulate blood sugar. People with high blood sugar often develop abnormal insulin levels and a condition known as insulin resistance. And people with insulin resistance actually may have lower levels of needed insulin in the brain even though they have higher levels in other parts of the body. All that means that brain cells may not be getting enough glucose, inflammation increases, beta-amyloid builds up and the cells die. Still another idea is that high levels of insulin compete with enzymes that break down beta-amyloid, resulting in the troubling protein building up in the brain. ... Even if diabetes simply represents a form of brain artery disease, it likely worsens or accelerates Alzheimer's caused by some other mechanisms."

Link: http://www.jsonline.com/story/index.aspx?id=493436

More on Enhancing Healing
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If you understand the biomolecular processes of healing, then you can step in to improve them. Many research teams around the world are doing just this. One such effect is examined here by Science: "Even on a cellular level, wound healing takes time. The body must target a large number of molecules called growth factors to just the right area to help repair the damage. ... The new tools are molecules called peptide amphiphiles. Once injected into the body, the amphiphiles self-assemble into long, thin nanofibers, which hang out in the wound area. ... in those given the amphiphiles, nanofibers assembled at the injury site and stayed put, drawing the body's own growth factors to the injury site. A month later, the team found that the hearts of the animals that received the amphiphiles pumped blood nearly as well as those of healthy animals. In contrast, the hearts of the control animals contracted about 50% less than normal. The same nanofibers also dramatically hastened wound healing in rabbits."

Link: http://sciencenow.sciencemag.org/cgi/content/full/2006/912/2

You Have Nothing to Lose But Your Mortality
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I encourage all of you to take a long, hard look at the reality of your own health and aging in the decades to come. At present levels of medical technology your future is a grim picture: there's nothing dignified, romantic or pretty about aging to death. If medical technology advances at a sedate pace, that grim picture might be put off for a few years - but it's still there, your own personal sword of Damocles.

In past eras, this was a matter to come to terms with as best you could. Fortunately, human beings are very good at living amidst the worst horrors; we'd all go mad if this were not the case. But we are now entering the decades of ever more powerful biotechnology and advanced medicine - decades in which the root causes of aging can be fully understood and effectively tackled. Our aptitude for living with the vast, ongoing suffering and death of aging is now working against us, leading to a lack of support for positive change and research into the defeat of aging:

Think about it for a moment: if I described the physical signs and eventual prognosis of aging to you, but you didn't know how old the person was that I was talking about, would you seriously consider the condition to be something nobody should look into addressing medically? Aging takes a healthy, vigorous person and saddles them with progressively increasing susceptibility to cancer, heart disease, diabetes, stroke, joint problems, overall weakness, and immune dysfunction and eventually kills that person. Without fail.

Yet it is now the case that the right scientific programs backed by the right levels of funding could greatly extend the healthy human life span rapidly enough for us to benefit. We know enough to get started - this is not a time for modest goals and conservatism. This is a time to unleash the full potential of the biotechnology revolution on the cause of more death and misery than anything else in this world: age-related degeneration.

Folk like you and I don't have to stand on the sidelines and hope for more results, or for more scientists to get to work. Organizations like the Methuselah Foundation offer powerful ways for us to band together and fund or encourage effective research into defeating aging. The MPrize for longevity research is the best present way for you to place a dollar in the pot to inspire many more dollars of aging research funding. People like you and I have already pledged millions to this cause, and in doing so are changing the world.

Those folk new to the Methuselah Foundation community, healthy life extension or the Strategies for Engineered Negligible Senescence might not realize that it is only very recently that scientists have felt able to talk seriously about tackling age-related degeneration. For the longest time it has been the case that discussing therapies for aging was the "instant death third rail of grantsmanship" as one researcher wittily put it. Funding in science is a very conservative process, taking place within a very conservative culture; aging research is no exception.

We at the Methuselah Foundation like to think that Foundation initiatives - powered by the generosity of our donors - have moved the boundaries of the discussion in the past few years. In this, we have helped to provide cover for scientists in the gerontology community to say openly what they have been willing to say in private all along - that science can defeat aging, and we should get started as soon as possible. The first step on any road is to be able to talk about the destination without risk of censure - it is a shame that is has taken so long and so much effort to get to this point.

So take a moment to look at just how much could be done for the future of your health and longevity - and step up to donate to make it happen. How many people throughout history have really, truly had a chance to band together to buy additional years of healthy life? Yet this is exactly where we stand today; we can buy research that will extend our healthy life spans.

Think about it. You can't take your money with you when aging claims your life, after all. In donating to encourage and fund ambitious, directed longevity research, you have nothing to lose but your mortality.

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Artificial Kidney Technology
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The MIT Technology Review looks at the technology base that will - in years ahead - lead to entirely artificial organs to replace failing or age-damaged kidneys: "Next-generation membranes, now being engineered, will have more than 100,000 pores or slits per square millimeter and provide more than 10 times the flow. An implanted device carrying several hundred square centimeters of this next-generation membrane [should provide] about one-third of normal kidney function. ... it remains to be seen if the [researchers] can squeeze their filtration systems into a package small and robust enough for implantation. ... their goal to more precisely emulate the function of the kidney is right on - and a welcome alternative to the incremental improvements in more conventional technologies that have dominated dialysis developments for the past 20 years."

Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=17493

The Silver Book
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Those of you who like to dive into the data should find much of interest at the Silver Book, a project of the Alliance for Aging Research. "When asked about their chances of having a chronic disease by age 65, just 4% of Americans select the correct range (81%-90%) from a set of possible answers read during the survey. ... Just 10% of the American public correctly estimates their chances of getting cardiovascular disease (61%-70%) by retirement age and most vastly underestimate their chances (39% are 20 points off or more). ... The Silver Book is an almanac of hundreds of facts, statistics, graphs, and information from close to 100 agencies, organizations and experts. It is a searchable database that is constantly updated and expanded in order to highlight the latest research and data on the burden of chronic disease and the value of investing in medical research." Would support for aggressive healthy longevity research increase if more people grasped the impact of aging on their health and livelihood?

Link: http://www.silverbook.org/

A Little Mitochondrial Science
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A little mitochondrial science for you today, culled from the interesting material posted to sci.life-extension. A great deal of investigation is taking place into damage and decline of mitochondria, and how it relates to age-related degeneration, frailty and illness. The more that researchers understand of the biochemistry at the root of this process, the sooner medical science will deliver therapies to put a stop to this aspect of aging. It's just like fixing up a car: if you know how to do it, you can do it, and your car lasts longer as a result.

Direct repeats in mitochondrial DNA and mammalian lifespan:

Mitochondria have long been suspected to be among the leading determinants of aging due to their functional importance and accelerated deterioration caused by accumulation of mutations in the [mitochondrial DNA (mtDNA). Direct repeats are known to contribute to deletion formation in mtDNA and are a powerful source of reactive oxygen species (ROS)-independent mutagenesis. To evaluate the potential importance of homology-based deletion formation, we have analyzed the association between direct repeats in the mtDNA sequence and the lifespans of 65 mammalian species. Here, we report a significant negative correlation between the mutagenic potential of direct repeats and the mammalian lifespan, which is especially evident in closely related species.

Evidence for Selective Mitochondrial Autophagy and Failure in Aging:

Autophagy is a major intracellular degradation/recycling system ubiquitous in eukaryotic cells. It contributes to the turnover of cellular components by delivering portions of the cytoplasm and organelles to lysosomes, where they are digested.

...

autophagy plays an important role in the degradation of excess or injured organelles, including mitochondria. To test the hypothesis of an involvement of a decrease in autophagy in the process of aging, we explored the antiaging effects of pharmacological stimulation of autophagy on the age-dependent accumulation of 8-OHdG-rich mitochondria in rat liver.

...

Results showed that drug injection rescued older cells from the accumulation of 8-OHdG in the mtDNA in less than 6 hours, but no significant decrease in the level of cytocrome c oxidase activity was observed. Together, these data provide indirect evidence that 8-OHdG might accumulate in a small pool of mitochondria with increasing age rather than be degraded by the autophagic machinery selectively.

These are confirming studies, elaborating and investigating the details of what is already generally known. Of such modest steps is progress built.

Meanwhile, the Methusalah Foundation has commenced research into SENS technologies that might offer a direct path towards preventing damage to mitochondria.

Mutations to the mtDNA inevitably accumulate leading to dysfunction of mitochondria, and contributing to aging of the organism. The goal of MitoSENS is to obviate mtDNA mutations by expressing the mtDNA genes from the nucleus.

Fortunately, we would be completing a process that evolution has already started.

The mitochondrial genome originally had thousands of genes, but evolution has reduced it to a mere 13 (protein encoding) genes in humans. By studying how nature transfered expression of other genes from the mitochondria to the nucleus, we can identify the necessary steps to transfer the remaining 13 genes (in humans).

This is a small amount of funding and research time at first, made possible by generous donations to the Foundation, but these efforts will expand. They join other more direct research initiatives, such as the wholesale replacement of damaged mitochondrial DNA via protofection. One of the central points of SENS is that while our knowledge is far from perfect, we know enough to get started on the development of effective, scientific anti-aging technologies today.

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From the Longevity Dividend Symposium
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Dave Gobel of the Methuselah Foundation was close enough to catch the Longevity Dividend Symposium today. From emails sent at the scene:

After happy introductions, Jay Olshansky gave a summary of the article in The Scientist:
  • There are lots of old people globally
  • We are facing a huge global crisis in baby boomers getting old
  • If we fund the delay (emphasized this word) of aging we can save more than if we cured every other disease of aging outright
  • He declared unreservedly that he/they were NOT talking about reversing aging or speaking of outlandish extensions such as 120, 150, 500 or even a 1000 years

Leonard Guerente gives a survey of calorie restriction...more later.

...

President of AAAS Dr. Alan Leshner says that we must deliver on the longevity dividend because he made a promise to his first grandchild born last week that he was going to be there for the younster for many years offering unsolicited advice. The first whispered bit of advice - "learn Mandarin."

The question is only "how fast will it happen." The need is more for more "gold" as we enter the golden age of aging research from the individuals making decisions in the Senate halls where this meeting is being held.

Dr. J Goodwin of "Help the Aged Foundation" in the UK stated that the recent report to the house of Lords - "Aging : Scientific Aspects" - expressed the observation that funding for aging was diffuse and was dangerously underfunded. The Chancellor of the Exchequer stated that the number one problem facing the UK, before global warming and terrorism, was the looming explosion of the aging.

He further averred that while the UK is far behind the US in funding aging research, the EU is investing 4 times less than the UK in aging research. It spends all its time and effort trying to beat the US economically with aerospace, arms, biz and pharma research - and thus leaves aging research at diffuse and tiny levels.

...

Presentations and slides of this conclave will be available as a podcast and been videotaped. They will be on the Alliance for Aging website - Dan Perry, the Executive Director, is one of the minds behind the symposium.

The Alliance for Aging website has a press release for the occasion, as well as the endorsed version of the Longevity Dividend proposal letter (in PDF format).

This event is very illustrative of the path of moderation above all else; when all immodest goals have been swept from the table - to keep the most conservative portion of the big tent happy - one can be certain that any chance of great success has been swept away with them.

Equally, it is a sign of the success of the Methuselah Foundation, SENS and other, similar advocacy, that any effort of this ilk must go to lengths to disclaim more ambitious goals. I'll be happy to see more of that taking place, along with the awkward questions that will come to those on the moderate path when millions and tens of millions are spent on mainstream, journal-published, scientific research seeking greater goals in healthy life extension.

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Announcing MitoSENS Research
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Last year the Methuselah Foundation commenced modest donor-funded biotechnology research applicable to the Strategies for Engineered Negligible Senescence - making a start on learning how to repair age-related damage so as to extend the healthy human life span. That LysoSENS research has been moving on apace. Now, the Foundation has announced the second line of research - MitoSENS. "Mutations to the [mitochondrial (mtDNA)] inevitably accumulate leading to dysfunction of mitochondria, and contributing to aging of the organism. The goal of MitoSENS is to obviate mtDNA mutations by expressing the mtDNA genes from the nucleus. Fortunately, we would be completing a process that evolution has already started. The mitochondrial genome originally had thousands of genes, but evolution has reduced it to a mere 13 (protein encoding) genes in humans. By studying how nature transfered expression of other genes from the mitochondria to the nucleus, we can identify the necessary steps to transfer the remaining 13 genes."

Link: http://www.methuselahfoundation.org/index.php?pagename=mitosens

The Conservative Case For Immortality
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It has to be said, I'm not sure why there has to be a conservative (in the political sense) case for immortality - but given that there now is, TCS Daily is where you'd expect to find it. Politics is indeed life for some people. "When it comes to life extension, many conservatives - without otherwise abandoning their pro-life credentials - turn out to be 'pro-death' in the sense of opposing as at least unwise or imprudent any serious attempt to slow down, halt, or reverse the aging process. ... But they may want to temper such instinctive reactions because, perhaps surprisingly, there are genuinely conservative arguments for life extension. Central to any conservative social agenda - using Russell Kirk's principles as exemplary - are desires to inculcate order, temperance, and prudence. And all of these are well served by encouraging longer lives, not shorter ones." The most interesting thing to me is that the author feels no need to emphasise or explain at length that healthy life extension is plausible and possible - that is progress from the advocate's viewpoint.

Link: http://www.tcsdaily.com/article.aspx?id=091206B

What Next For Regenerative Medicine
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An interesting paper in PLos Medicine looks at the best next steps for regenerative medicine. It's intended to focus on the "developing world" (or, more accurately, the "world sabotaged by corruption and willful economic ignorance") - but the recommendations come across as common sense for the field as a whole, no matter what region you might live in. A panel of experts put forward their view of "the ten most promising applications of regenerative medicine for improving health in developing countries ... Top-ranked application: Novel methods of insulin replacement and pancreatic islet cell regeneration for diabetes. ... Second-ranked application: Autologous cells for the regeneration of heart muscle after myocardial infarction and cardiomyopathies. ... Third-ranked application: Immune system enhancement by engineered immune cells and novel vaccination strategies for infectious disease."

Link: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030381

Towards an Artificial Cornea
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From EurekAlert!, news of more progress towards replacement parts for the eye: "Myung's project [was] to design, fabricate and characterize a bioengineered cornea based on the dual-network hydrogel. The result was a disc with a clear center and tiny pores populating the periphery. Myung calls the pores engineered into his artificial cornea the 'homes' he built for cells that need to infiltrate the artificial lens and integrate it with surrounding natural tissue. ... If you build it, they will come. The cells move in, and they bring furniture too - meaning the collagen they secrete. They even 'remodel.' ... Collagen binds to the edge of the synthetic disc and forms a junction between natural and synthetic tissues. Then a clear layer of epithelial cells grow over the disc. ... Animals have tolerated artificial corneas with no problems in trials as long as eight weeks. [The] material remains perfectly clear."

Link: http://www.eurekalert.org/pub_releases/2006-09/su-aac090806.php

The Media, Novelty and Healthy Life Extension
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A short comment caught my eye in a post on that recent research into the gene p16INK4A, aging and cancer:

This ought to be front-page news: I can't quite seem to figure out [why] Aubrey De Grey and company hasn't been interviewed a dozen times this week...

The culture of mainstream media has some interesting quirks when it comes to novelty; journalists are always chasing the superficially new. If there is no aspect of a story that can be spun as new in some way, the level of interest drops dramatically. Biomedical gerontologist and healthy life extension advocate Aubrey de Grey has been interviewed and quoted many times in the past year - so that is now done and done in most media circles until some new twist is presented.

Part of the skillset inherent in success as an advocate (and even more so for public relations folk in the corporate and research worlds) is divining just what can be presented as new and shiny to catches the eyes of the media magpies. It's not a job I would enjoy. It all too often degenerates into a game of paint and lies, in which the original goal becomes secondary - that's a fate I'm happy to avoid, or at least leave up to the professionals.

A great deal is going on behind the scenes at the Methuselah Foundation, the nonprofit, donor-funded longevity research and advocacy organization chaired by de Grey. Sadly for the community of supporters, most is of that brand of endeavor that cannot be announced until all the ducks are in line. You're just going to have to take my word for it that interesting things will be springing forth before the end of the year.

Then it will be back to the media with a vengence, genuinely new matters and progress in hand - something I won't feel bad about in the slightest.

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ACT As Funding Barometer
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The health of Advanced Cell Technology (ACT) is still, I think, a fair barometer of support and funding for embryonic stem cell research. The latest from UPI: "Advanced Cell Technology said Friday it has closed two financings generating approximately $13 million in cash. ... ACT said it would also use the proceeds toward three therapeutic programs that the company said it hopes to bring to clinical trials, including therapies to treat degenerative eye disease, heart and vascular disease, and technology to regenerate skin damaged by wounds, burns and in surgical procedures." It seems that private investors have decided there is now little risk of US politicians criminalizing therapeutic cloning or otherwise directly suppressing freedom of research in ways that would impact companies like ACT.

Link: http://www.upi.com/HealthBusiness/view.php?StoryID=20060908-112800-1450r

To Defeat Frailty
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Viewpoints on aging - on therapies, what aging is, and how much can be done to stop it - continue to change for the better. From the San Franciso Chronicle: "Researchers are finding that frailty may not be the inevitable result of aging but rather is a preventable and perhaps treatable condition. The muscle weakness, exhaustion, and weight loss typical of frailty were until recently considered just byproducts of diseases and the general loss of vitality during one's advanced years. Now scientists are studying the condition in its own right." The article looks at very early first steps, both in opinions of aging and medical science. In the years ahead, we will be able to do far more to prevent aspects of age-related degeneration and thus extend healthy life span - but only if a foundation of widespread support and understanding for scientific longevity research is set down now.

Link: http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2006/09/10/MNGRIL07L01.DTL

Learning From the Slow Acceptance of Molecular Manufacturing
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What can we in the healthy life extension community learn from the experiences of advocates and planners of molecular manufacturing? From a pure advocacy point of view, work to advance funding and support for this sort of future nanotechnology is five or more years further along the classic path of growth, public awareness and education than our work for healthy life extension science. Battles that have already been fought in the nanotechnology arena lie ahead for organizations like the Methuslah Foundation and initiatives like the Strategies for Engineered Negligible Senescence (SENS) - unless we can steer our way to avoid them.

I and others have discussed this topic in the past, comparing Eric Drexler on the nanotechnology side with Aubrey de Grey on the healthy life extension side. As we all know, Drexler has not had a smooth ride of it in the past couple of years as folk raising funding for nanoscale engineering (i.e. early stage nanotechnology, quite different from the proposals put forward by the likes of Drexler and Robert Freitas) engaged in a rather nasty campaign of character assassination of both Drexler and the science of molecular manufacturing.

You'll find some more recent thoughts on this topic over at Responsible Nanotechnology:

NanoEnthusiast wrote on our blog yesterday, "I can't help but think that if all the radical ideas related to Drexlerian nanotechnology (i.e radical life-extension, nanofactories that can make anything) had not been talked about; then maybe the rather modest-sounding claim that one can build interesting nanostuctures out of diamond one atom (or dimer) at time would have been accepted more easily."

...

A few days ago I (Chris) was making a list of the reasons why molecular manufacturing might have met with such slow acceptance and determined resistance. Here are some:

  • Drexler committed the unforgivable sin of scientists: he wrote a popular book.
  • He published a catchy term for a horrifying scenario ("grey goo"). Drexler, and several other nanotech people, spoke in favor of cryonics.
  • Bill Joy published a scary anti-MM article just as the US National Nanotechnology Initiative was getting off the ground.
  • For a very long time, vitalism was a significant problem: the idea that machines can't make machines, only life can do that.
  • MM people sometimes cited non-MM-focused research as evidence of MM's feasibility, and the researchers often objected to that, especially once MM became controversial.
  • Drexler was too far ahead of his time, and for a while there was very little experimental evidence to back up his physics-based extrapolations. Even today, this is a weak spot. (Trouble is, once the evidence is all in, we'll be very close to building a nanofactory, with no time left for adequate policy discussion!) (Other trouble is, even where evidence existed, it was ignored--for a number of years, scientists made such broad claims of impossibility that they effectively declared biological life impossible!)

I think that retreating from well-founded predictions that are two steps ahead rather than one step ahead is neither acceptable nor helpful to advancing your cause. If you want to move the debate, educate people and retain your own self-respect, you have to tell it as it is. Being far out in advance of what others are willing to commit to in public - while still having the science to back your position - is the best thing you could be doing.

We advocates must work to turn what were once seen as unthinkable goals for radical life extension into the conservative, mainstream position on the future of medical research.

I have talked before about the merits of the suitable outrageous extreme as a cultural device for advancing the cause of healthy life extension. This device has been working, and working well. A few years of making a plausible scientific case for medical technologies capable of supporting healthy life spans of 1,000 years or more has already notably moved the debate. Supporters of healthy life extension in the mainstream can now openly discuss and advocate 10 and 20 year healthy life extension with no funding repercussions. We can certainly keep this process going, but progress is damaged by those who make the run to moderation, taking a vow of silence or accepting lesser research goals in return for funding. Every voice that falls silent makes it that much harder to gain support for our position.

I do not think that Drexler's woes and the attendant attacks on research into molecular manufacturing - and other two steps ahead nanotechnology such as nanomedical robots - are a function of Drexler's actions. Quite aside from the fallacies inherent in assigning responsibility for the actions of party A to party B, not to mention the creation of figureheads, I have a better theory. To my mind, this all stems from a collision of brands and namespaces. When I talk about nanotechnology or nanomedicine, I have to clarify what I mean. Nanotechnology has become such a broad term that it is meanless to invoke it without qualifiers (early, advanced, existing, future, etc). Are you talking about nanoscale engineered such as that under development for new cancer therapies to guide drugs with pinpoint accuracy? Or are you talking about molecular manufacturing and the future production of goods, atom by atom? There are many other shades and meanings.

Once you have a collision of namespaces, conflict is inevitable. We can see this in the healthy life extension community for the term "anti-aging." The actual details of conflict, personalities involved and so forth are somewhat irrelevant - it all stems from the brand collision and resulting issues with conservative funding sources, public perception, support and so forth. I think we can trace back all the real acrimony over the nanotechnology namespace to the point at which initiatives to gain large-scale public funding were obtaining results; some folk felt that Drexler and advanced nanotechnology advocates were reducing their chances of obtaining funding, and so went on the attack. Human nature at its worst, as usual.

So what can we learn from this? When it comes to initiatives like SENS, the MPrize or research directly supported by Methuselah Foundation donors, we should carve out our own novel names and brands. If we talk about anti-aging research or even aging research, we are engaging in a namespace collision with entrenched interests and their funding activities. You can get away with that while the sums are small, but real money changes the game.

Take a look at the Longevity Dividend initiative, for example. Assuming continued growth and success on the part of the organizers, it's easy to draw the parallels between this and the National Nanotechnology Initiative that sparked the attacks on Drexler and advanced nanotechnology. It makes sense to move the long-term, forward looking work of healthy life extension advocates out of the namespace - and firing line - of moderates who support short-ranged initiatives and goals.

Once large amounts of money are on the table, and the possibility of brand confusion is raised, there are always some few in the wider community who will actively attempt to harm legitimate scientific work over funding issues. They should be treated as they deserve, but let's remove the incentive for undesirable actions in the first place.

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He Did Nothing, But Neither Did You
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A light and fluffy article from the Guardian can be taken quite seriously at its heart: "He was the first yuppy president. But he did nothing to stop a process even more urgent than global warming: ageing. ... Clinton was our first yuppy president, and yuppies thought that we owned youth. Nobody else has ever been as young as us, and nobody else ever will be." We are entering an era in which every one of us can make a contribution to the fight against aging. Not on a personal level, because there's precious little you can do there at this time, but to support the science and research that will actually stop age-related degeneration in its tracks. You can contribute to the MPrize or the research supported by the Methuselah Foundation. You can get out there and encourage others to do the same. You can help show people just how close medical science is to successfully tackling the underlying causes of aging. If you don't do this, you'll only have yourself to blame if we fail to make meaningful progress in our lifetimes.

Link: http://www.guardian.co.uk/frontpage/story/0,,1868581,00.html

Biotechnology From the Labs
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A new mini-feature from the MIT Technology Review: short digests to explain the significance of selected research. Scientists "found that a drug similar to ones used to treat Parkinson's disease can spur growth of new neurons in the substantia nigra, the brain area damaged in the disease. ... Current treatments for Parkinson's disease replace or mimic dopamine, an important signaling molecule in the brain. But those treatments lose their effectiveness over time; boosting the brain's ability to make more of the dopamine-­producing cells could provide a more effective strategy. ... Ultimately, they hope to find compounds that will help replace cells lost in a range of neurodegenerative diseases, such as Alzheimer's and Huntington's."

Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=17415

Ouroboros on Sirtuins
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I suggest you steer yourself over to Ouroboros to take a look at a trio of recent posts on sirtuins, the present focus of much of the research into the biochemistry of calorie restriction.

Sirtuins and Senescence:

Two recent papers describe a relationship between the lifespan regulator Sirt1 (ortholog of the yeast Sir2p, member of the creatively named "sirtuin" family of proteins) and cellular senescence: As cells lose their ability to divide, they downregulate Sirt1.

...

The papers also suggest a connection between "lifespan" as it is considered in two different senses, proliferative/replicative lifespan (of a cell line) and organismal lifespan (of a body) - that are not necessarily synonymous, despite their interchangeability in some contexts (yeast) and the propensity of some scholars in the field to treat replicative senescence as though there were an evidence-based consensus that it is an explicit model for organismal aging per se.

Thank you SIR, may I have another:

Continuing with yesterday's sirtuin and aging theme, here are three more recent papers that further expand the Sirt1/aging literature.

Sirtuins in the mitochondria of the pancreas:

Sirt1 gets a lot of attention, and is unquestionably the best-studied of the human homologs of the canonical yeast SIR2 gene. SIR2 was originally identified in yeast as a Silent Information Regulator, a member of a multi-gene complex involved in repression of the silent mating type loci and in telomeric silencing. In the early 90s, Leonard Guarente's lab discovered that SIR2 also governs the replicative lifespan of yeast, allowing biogerontologists to deploy what the late Ira Herskowitz called the "awesome power of yeast genetics" into the field of aging. Since then, sirtuins (as the metazoan homologs of SIR2 are called: "sir-two-ins") have been shown to regulate lifespan in worms, flies, and the mouse. Most of these studies have focused on Sirt1.

...

Breathtakingly, there are five other sirtuins in humans that have barely been studied. Watch this space for further developments.

The utility of studying the biochemistry of cellular aging in yeast has grown greatly since 5000 different gene knockout varieties were created. Having the opportunity to study what each gene does in isolation - by suppressing or removing it - has been a large step forward towards developing a detailed blueprint for the cell. Such blueprints are the foundation for accelerated progress in all fields of medicine and biotechnology. This is precisely why scientists are accelerating their attempts to do the same for mice:

The National Institutes of Health has awarded a five-year cooperative agreement worth approximately $23 million to a consortium of the Children's Hospital Oakland Research Institute; UC Davis; and the Wellcome Trust Sanger Institute, England.

The group plans to create lines of embryonic mouse stem cells in which 5,000 individual genes will be systematically turned off, or "knocked out." Those embryonic stem cells will then be used to breed live mice that lack those genes.

...

Scientists have been making knockout mice since 1988, but so far these cover only about 5,000 genes, or about 25 percent of the mouse genome, said Kent Lloyd, a principal investigator on the grant and associate dean for research at the School of Veterinary Medicine.

"The technology is now here to do this on a high-throughput basis," Lloyd said. "Within five years, through this and related projects around the world, scientists will have access to knockouts of the whole mouse genome."

Ten thousand genes that are most closely shared between mice and humans are a high priority for the NIH. Studying how those genes work in mice can give insights into human health and disease.

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Mobilizing Your Stem Cells
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It's quite possible that the transplants - autologous and otherwise - of first generation stem cell therapies will give way to manipulation of biochemical signals in the body. Manually moving stem cells from point A to point B is all we can presently reliably accomplish, but that won't be the case for too many more years:

Recently, researchers at Washington University School of Medicine in St. Louis demonstrated that a drug called AMD3100 can mobilize angiogenic cells from bone marrow of human patients in a matter of hours instead of days, as was the case with a related agent called G-CSF.

Angiogenic cells reside mainly in the bone marrow, and when mobilized they can circulate in the bloodstream, homing to sites of injury and helping repair and regrow blood vessels that bring oxygen and nutrients to tissues.

...

"It might be better to let the appropriate cells find their way through the circulation to the site of injury or low oxygen," he says. "That way you enhance a normal repair mechanism instead of using the brute force of injecting a mixture of many cell types from bone marrow into the affected area."

A wide range of research - both old school drug discovery and more guided approaches based on first understanding the biochemistry involved - is aimed at better control over healing mechanisms such as the disposition and activity of stem cells.

Evolution is not much of an optimizer in comparison to directed, intelligence. The existing mechanisms of our body are open to improvement in all sorts of ways - such as convincing stem cells to get to work in the right place when they would otherwise lie dormant.

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Longevity Dividend, September 12th
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A reminder from the newswires: the Longevity Dividend symposium in Washington DC is coming up on the 12th. "The Alliance for Aging Research, along with prominent scientists, will call for governments and health care organizations to invest in the extension of healthy life in order to produce a 'longevity dividend.' Scientists will urge U.S. policymakers to invest in scientific discovery to slow aging in humans. As lifespan dramatically increases, so does national health care spending on a wave of chronic diseases and disabilities such as Alzheimer's, congestive heart failure, cancer, stroke, diabetes and vision loss. Speakers will address such topics as: when science will be able to slow aging and the cost; can older populations make nations both healthier and wealthier; and international perspectives." The list of endorsements of the Longevity Dividend position statement is growing rapidly, by the look of it.

Link: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/09-08-2006/0004429257

Stem Cells for Enhancement?
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If the introduction of more stem cells helps when you're aged and injured, could it also help you push off age-related degeneration, or otherwise improve the duration of some youthful capacities? The profit motive in professional sports seems the most likely way to answer that open question, given that enhancement (and even prevention, all too often) isn't on the regulatory agenda for mainstream medical research funding. "There's a spin-off technology from stem cells that could produce super-athletes ... injecting stem cells into healthy muscles might increase their size and even restore them to their youthful capacity. ... You could potentially find a 40-year-old man with 20-year-old legs." Sadly, there's all to much to aging that you can't fight with forms of regenerative medicine or enhancement via boosting stem cell activity - if such proves plausible. That shouldn't stop us from trying for those gains that can be had.

Link: http://www.iht.com/bin/print_ipub.php?file=/articles/ap/2006/09/07/sports/EU_SPT_Doping_Stem_Cells.php

Attacking Neurofibrillary Tangles
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Most Alzheimer's research is focused on understanding and eliminating amyloid plaque, although there's some evidence of late that the plaque itself may not be the best point of aim for potential therapies. Another line of investigation revolves around neurofibrillary tangles. From Forbes, news of progress on this front: "In tests with mice and fruit flies, an enzyme appeared to both eliminate the tangles and reduce the brain's decline. ... It's not clear if tangles hurt brain cells or are just a symptom of a dementia problem. ... The point is that they're totally correlated with neurodegeneration in Alzheimer's disease, and in a number of other dementias. ... In some forms of dementia, tangles are 'the whole story' because amyloid plaques aren't present. ... it will likely take years for a drug for humans to be developed ... research into tangles has lagged behind research into ways to combat amyloid plaques."

Link: http://www.forbes.com/forbeslife/health/feeds/hscout/2006/09/07/hscout534782.html

Cause of Angiogenesis in AMD
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EurekAlert! notes another step towards preventing age-related macular degeneration (AMD): "Uncontrolled blood vessel growth (angiogenesis) is a major contributor to the development of age-related macular degeneration (AMD) ... [researchers] found that the molecule, Carboxyethylpyrroles (CEPs), attaches to proteins found in the eye, triggering the uncontrolled growth of blood cells. ... The researchers did in vivo animal studies with membranes from chicken eggs and rat eyes and found that CEPs attached to proteins induce angiogenesis. They also found that the protein part of CEP-protein adducts is not important for producing the growth of the blood vessels. Rather, the actual CEP is the cause of angiogenesis. In an attempt to block CEP from triggering the angiogenesis process [we] are now trying to find the receptors - the keyholes - in the retina cells that are activated by CEPs. We are also designing drugs that can mop up the CEPs or prevent their formation."

Link: http://www.eurekalert.org/pub_releases/2006-09/cwru-cac090606.php

Managed Expectations
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If there's one unerring sign of progress in healthy life extension, life spans and therapies for age-related conditions, it's an upward trend in complaints about the specifics of age-related degeneration. Perspective is a lost art. An article from the Australian media is rather representative:

The average Australian man can now expect to spend 5.4 years of his life with a severe disability, needing help to perform the most basic tasks such as washing or going to the toilet.

The latest Australian life expectancy figures, released today, show that while overall life expectancy has again risen, the average man will also spend almost two decades - or 18.6 years - with a lesser disability.

One has to keep a sense of perspective; if you look back at the past, the present state of affairs is a great improvement - and getting better. The serious age-related diseases are more successfully treated than ever:

Men and women who make it to age 75 in 2006 can expect to still be around in 2016 and 2017, respectively. At age 85, the odds are good that you'll reach 91. ... people who study aging trends believe that life expectancies for the old will continue to grow longer. The main reason is that the three biggest killers of older people - heart disease, cancer, and stroke - are being treated more successfully.

On the flip side of the coin, we should keep realistic expectations when it comes to the present pace - and best possible pace we can engineer - in medical progress. There are no miracles; there is steady hard work that produces commensurate steady advances in infrastructure and capabilities. By way of an example, a recent article on the death of a stem cell patient and advocate Ian Rosenberg gives an idea as to the sort of gains we can expect from much-hyped first generation stem cell therapies:

Ian Rosenberg, who was diagnosed with heart failure five years ago and given just two months to live before he opted for the therapy in Germany, passed away last Friday aged 70.

By 2003, his heart failure was severe and only seven per cent of his heart was functioning.

He was referred to a consultant cardiologist who had been investigating stem cell research and was later referred to the Johann Wolfgang Goethe Hospital in Frankfurt, where a team was conducting human trials, taking adult stem cells from bone marrow in the hip and injecting them into the main artery of the heart.

...

Stem cell therapy transformed Ian's life. It gave him three years he would never otherwise have had.

This is in line with the sort of results being seen in similar trials and treatments around the world. It's both a great advance and modest incremental improvement over what came before. The technology and its results will become better with time and research - and none of that is reason to disparage what is now, or the field in general.

The bottom line: what is it worth to you to be alive and inconvenienced, as opposed to alive and disabled, or dead? All progress towards longer lives and the defeat of age-related degeneration should be welcomed and encouraged. If a transition period of lesser disabilities and annoyances is the price to pay for the focus on dealing with major concerns first, then so be it.

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Smad7, Aging Skin and Cancer
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(From the Medford News). "In humans, scientists and medical doctors documented the aging skin phenotype a long time ago, and the [gene] Smad7 over-expression in aged skin was reported a few years ago, but nobody knew whether these two events had any link ... They found that Smad7 over-expression shifts the epidermal stem cell differentiation program from forming hair follicles to sebaceous glands, causing the mice to exhibit balding and oily skin. ... independent of its normal role in blocking signaling from a group of genes called Smad, Smad7 shuts down signaling of another group of genes called Wnt ... Wnt signaling is critical for organ development, but if Wnt signaling is too active, it also causes cancer." Once again, aging or cancer is the choice in an aspect of our present biochemistry; many of the changes seen in aging turn out to have something to do with cancer suppression.

Link: http://www.medfordnews.com/articles/index.cfm?artOID=332397&cp=10996

More on Aging, Cancer, Stem Cells and p16INK4a
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A fair amount of chatter is taking place over recent research into the protein p16INK4a and the gene producing it. The name indicates it is an INhibitor of cyclin-dependent Kinase 4A; romantic, slipstreamed naming schemes are the first casualty of complexity in science - and it doesn't get much more complex than biochemistry. I noted the EurekAlert! release at the Longevity Meme, but the HHMI News article is an easier read and more to the point as to what folk are thinking could be done with the research. See what you think:

A single molecular switch plays a central role in inducing stem cells in the brain, pancreas, and blood to lose function as they age, researchers have found. Mice lacking that switch show considerably reduced aging-related decline in stem cell function and tissue regeneration.

...

People tend to think that old tissues have less regenerative capacity because they are wearing out. This work shows that they are not just wearing out; they are actively shutting themselves down.

...

While the finding could ultimately lead to drugs to slow or reverse degeneration in the brain and other tissues, the researchers cautioned such treatments would have to be balanced against the chance of increasing cancer risk in patients.

...

I think if you asked before these studies whether you could delete a single gene and rescue stem cell function in multiple tissues, and neurogenesis in an old brain, many people would have said that aging is such a complex phenomenon that you would not get a significant effect.

This last quote aptly illustrates why there is great interest in this research - it's always exciting to find a common trigger for many different aspects of aging biochemistry.

Much of the discussion presently taking place relates to evolutionary explanations for this mechanism: the well known trade-off between aging and cancer that are seen in many cellular mechanisms:

Morrison theorized that p16INK4a is a suppressor of stem cell function that evolved as part of the regulatory machinery that also includes proto-oncogenes that encourage cell proliferation. "We are all evolutionarily selected to, on the one hand, maintain regenerative capacity of our tissues through adult life so that we can repair our cells and survive injuries - while on the other hand, limit proliferation in our tissues with age, so cells don't divide out of control, causing cancers," he said. "And the way that we achieve that balance is by having proto-oncogenes that promote proliferation come into balance with tumor suppressor genes that inhibit proliferation. This work shows one way that this balance changes with age.

...

While these tumor suppressor mechanisms don't even exist during fetal development, where cells must divide rapidly, it makes sense that they become stronger in old age, when we are more at risk of getting a cancer. So, the benefit is that genes like p16 allow us to get older before we get cancer, but the bad news is that they make us lose function with age.

Beyond the whys and wherefores, the temptation is, as always, to latch onto the latest idea and what-if your way forward. What if this all works much the same way in humans? What if reliable cancer therapies pan out by 2015? Wouldn't that make therapies directed at p16 worth exploring as a path towards healthy life extension?

From where I sit on the sidelines, it seems that tinkering with the structure of the engine - building better components for hot-swapping on the go - is not as utilitarian a path forward as developing the means to repair accumulated age-related damage to the present engine. Improving components is a matter of slowing aging; repairing damage is a matter of preventing and reversing aging.

Look at it this way: you might gain as much in the first decade of full-on commercialization from the results of either of these two different philosophies of development, but replacing a component of your biochemistry in order to slow aging is a one-time deal per component. You change your biochemistry, and there you go, running on the same old timer with a few extra ticks of the second hand. With a working repair technology, you can keep coming back again and again until something else becomes the limiting factor to your health and life span.

That said, there's no such thing as useless knowledge in biochemistry; it's all grist for the mill of the next few decades. We'll be hearing more about p16INK4a, I'm sure, as research into aging, cancer and stem cells continues to overlap and reinforce mutual progress.

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A Mechanism of Cellular Aging
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Via EurekAlert!, a biomechanism of cellular aging: "Three separate studies confirm a gene that suppresses tumor cell growth also plays a key role in aging. The researchers found increasing concentration, or expression, of the gene p16INK4a in older cells; these aging cells worked poorly compared to young cells and remembered their 'age' even when transferred from old mice to young mice. ... The studies indicate that certain stem cells lose their ability to divide and replace themselves with age as the expression of p16INK4a increases ... even though old mice lacking p16INK4a show enhanced stem cell function, they do not live longer. This is because p16INK4a is an important cancer-suppressor gene, and mice lacking p16INK4a develop more cancers than old, normal mice ... p16INK4a loss was associated with an improvement in some but not all of the consequences of aging." The age-old story: cancer or aging, pick one. Setting forth to repair the accumulation of damage seems like a better plan than tweaking the mechanism for greater performance at this point.

Link: http://www.eurekalert.org/pub_releases/2006-09/uonc-sfg090506.php

The State of Glycosylation Engineering
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An interesting article on the state of glycosylation biochemical engineering can be found at Chemical & Engineering News. A great deal of expertise and practice in the use of biochemistry to perform and reverse glycation reactions exists, by the look of it. "Carbohydrate chemists and biochemists tend to be controlling personalities. They aren't satisfied with the way sugar groups are attached naturally to glycosylated proteins and natural products. These scientific drill sergeants think they can do better. So they're busy most days devising new ways to whip fractious glycosylated biomolecules into shape. And these control freaks are actually making remarkable progress at achieving their desired results." All this expertise could be turned towards developing the means of dealing with advanced glycation endproducts (AGEs) and their role in age-related conditions.

Link: http://pubs.acs.org/cen/coverstory/84/8436glycosylation.html

Rheumatoid Arthritis and p38
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The New Scientist reports on a recent PLoS Medicine paper: "People with rheumatoid arthritis tend to die about five to 10 years earlier than others, so this is not just feeling stiff in the morning ... Nerves in bodily extremities, such as hands and feet, can produce compounds that increase inflammation. The new results suggest that p38 [an enzyme involved in joint inflammation] is an early part of the pathway that sends signals from the central nervous system to these distant nerves ... Clinical trials are currently underway to test if blocking p38 throughout the body can stop the progression of arthritis in humans." Chronic inflammation is no joke when it comes to consequences for your health and life span; it seems to be a potent source of age-related damage.

Link: http://www.newscientist.com/article/dn9994-spine-injection-cuts-arthritis-inflammation.html

Where are the Complex Artificial Organs?
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Where are the complex, functional artificial body parts - the artifical eyes, hearts, lungs and so forth? The state of the art here is still pretty primitive when it comes to matching the utility of your present biological apparatus, even when those organs are at the end of their rope. To pick one example, this is where artificial hearts stand, more or less - anything that has worked its way through the FDA process is a generation behind what is presently in the labs:

Today the U.S. Food and Drug Administration approved the first totally implanted artificial heart for patients with advanced heart failure in both of the heart's pumping chambers. The device is intended for patients who are not eligible for a heart transplant and whose life expectancy without the device is only a month.

In other words, you can expect to do somewhat - but not greatly - better than a run of a month or so with one of these devices. No doubt the prospects would be better for someone less terminally damaged, but still. Compare that with the sort of early results obtained from regenerative medicine; it looks to me as though the prospects for biological repair are brighter than those for artificial organs - at least for the decade ahead.

Artificial replacements for portions of the eye are much the same state: the early functioning technologies are fairly crude in comparison to results from early regenerative medicine.

The marketplace for research funding appears to have come to much the same conclusion in these years of advancing stem cell science; resources devoted to regenerative medicine outweigh resources for the development of complex artificial organs.

Some small improvement is far better than nothing at all if you benefit from any of these technologies, but they are all steps on the road - even if one path seems shorter than the the other, at least until the first way station. In the long run, this will look like a tortoise and hare sort of race. Eventually we will be able to build artificial organs and bodies far more impressive, capable, adaptable, inexpensive and useful than our present biology. That much is written on the wall, even if everyone argues over the timelines. "Eventually" is not next year or next decade, however, and the pressing problems of aging and degeneration must be meaningfully addressed in the here and now - or else those of us reading this now won't be around to see "eventually."

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Stem Cells In the Heart
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From News-Medical.net, a look at further discoveries in adult stem cell populations: "We have first demonstrated in humans that, as in the animal model, failing hearts still possess cells that show all the features of stem cells in vitro. Cardiac stem cells (CSC) are indeed able to proliferate giving rise to other stem cells (property named self-renewal); they can differentiate into all the cells composing the cardiac tissue, for example myocytes and endothelial cells, (property named multipotency)." The authors show that the stem cell populations in damaged hearts differ from their counterparts in healthy hearts. That doesn't tell us what is cause and what is effect, however. It does raise the possibility of existing stem cells being mobilized in some way rather than the use of transplanted stem cells (autologous or otherwise) for therapy.

Link: http://www.news-medical.net/?id=19887

Korean Funding For Longevity Research
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Via the International Herald Tribune: "The [South Korean] Science and Technology Ministry will provide [US$20.9 million] to scientists over the next nine years for research to develop technologies to help people avoid the effects of aging. The main areas for the work will be how to improve cardiovascular fitness, prevent diabetes and other aging-related diseases and prevent oxidation-reduction reaction in cells, the main cause of aging ... This project is aimed at helping people live long, healthy lives. We gave this project a higher priority when selecting new projects, considering the problem of aging society." Allowing for mangling of the science after multiple layers of translation, this sounds like a trial run of funding for something similar to the Longevity Dividend research proposal. The open acknowledgement of the goal of healthy life extension is very positive. If you can talk about that goal in grant proposals and still get funded - by no means the case in most funding infrastructures - better and more effective longevity science is only a step away.

Link: http://www.iht.com/articles/ap/2006/09/04/asia/AS_GEN_SKorea_Fountain_of_Youth.php

Progress Towards Artifical Eyes
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I'm going to go out on a limb and predict, from progress in the past few years, that regenerative medicine for age-related blindness will be practical and effective before artificial eyes arrive on the scene. Which is not to say that the present state of bionic vision is bad: extremely limited vision is far, far better than no vision, and this technology will only get better with time. From COSMOS Magazine: "Early tests of a 'bionic eye' developed by Australian researchers have successfully stimulated limited visual sensation in people suffering a rare form of genetic blindness. ... the prototype bionic eye was a low-risk device for patients because it sat on the eye's surface and did not require invasive surgery. He said it was an exciting development for people suffering conditions such as retinitis pigmentosa, an irreversible genetic condition where the retina's cells gradually die but the optic nerve survives."

Link: http://www.cosmosmagazine.com/node/622

The 3rd International Conference on Healthy Ageing & Longevity
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The program is now available for the 3rd International Conference on Healthy Ageing & Longevity, which takes place next month in Melbourne, Australia.

This conference series is shaping up to be a much broader look at aging research and related healthcare communities in comparison to its earlier focus on longevity science, at least from my point of view. The organizers have done a good job of broadening the stage, and have broadened it all the way into a moderately representative reflection of aging research and healthcare spending proportions around the world. In other words, a great deal on present work to try and meaningfully manage the consequences of age-related degeneration and death, and damn little on how to change the present state of affairs and its accompanying toll of suffering and death.

We live in a world accustomed to a terrible, ongoing holocaust; tens of millions of deaths each year, and hundreds of millions of others live in increasing suffering, pain and disability. The key word here is "accustomed" - how else to explain the vast resources devoted to the doomed attempts to cope, and so little put towards change in the form of better medical science?

After a certain point, I feel that big tent affairs are perpetually in danger of collapsing into a big heap of talk and no progress. Whenever you broaden the tent, you're going to get more talkers than doers - and I see a great deal of hot air in between the science in that conference schedule. Everybody is willing to talk about the present, but far too few are willing to get out there and make the future.

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AARP The Magazine on Healthy Life Extension
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The magazine of the AARP - once upon a time the American Association of Retired Persons, but retirement is changing as healthy life span lengthens - recently published a set of articles on health, aging and healthy life extension. They're remarkably good for mainstream fare; even the diet article is largely focused on the scientific backing for calorie restriction. The science throughout is broad mainstream, meaning metabolic research and efforts to slow aging (or just prevent or cure age-related disease) rather than efforts to reverse aging by repairing age-related cellular damage. Also, you'll note the recognition that no medical technology available today is proven to do much more for general health and age-related decline than exercise and calorie restriction. Take look and see what you think:

AARP The Magazine Special Report: Living Longer

For all the research, the best way to be a long-lived human like Ed Rondthaler seems relatively uncomplicated: eat an antioxidant-rich diet, avoid obvious environmental pollution such as cigarettes, get lots of exercise, and find ways to cope with stress. "Some would have you believe that the key to longevity is in a pill bottle," Sprott says. "My view is that it's not there. All of those medicines and vitamins that are supposed to make you live a very long time are modern-day snake oil. The real key is diet and exercise. We don't have anything that comes out of a pill bottle that does a better job."

...

"The potential here is not just to make people live longer. That's not the goal, even," says molecular biologist Lenny Guarente, Ph.D., of the Massachusetts Institute of Technology. "The goal is to find ways to significantly mitigate the major diseases of aging. And that would include cardiovascular disease, cancer, diabetes, neurodegenerative disease."

The standard shying away from any public endorsement of extending human life span is in evidence where scientists are quoted, sadly. Sooner or later, researchers in the mainstream are going to have to grow a backbone on that topic - until they do, funding for meaningful progress will continue to be hard to find. If Olshansky and Miller can do it with the Longevity Dividend proposal, so can the rest of you folk with conservative grant relationships to nurture! While we're on the topic, I recommend you read Aubrey de Grey's thoughts on this conservatism in the mainstream of gerontology.

Also noteworthy: regulation is one overriding reason as to why little or no funding is presently devoted to any of the now obvious scientific paths to extending healthy life span.

So why aren't scientists attempting to develop a true longevity pill? For starters, the Food and Drug Administration, which approves prescription drugs for safety and effectiveness, doesn't recognize aging as a disease. Therefore, the agency will not consider a pill that simply extends life. And being realistic, says Peter DiStefano, Ph.D., chief scientific officer of Elixir, "it's not like we're going to run out and find you a pill that you can pop and look ten years younger in a few months."

In other words, you won't get funding unless you're addressing a specific, named condition. Put differently, no funding for you unless you're patching up holes in the dam long after the root cause of the problem has gone untended and grown into a serious, life-threatening issue. The entire regulatory structure is set up to actively discourage the better approach of repairing root causes prior to the development of age-related conditions. All the more reason not to have a regulatory structure - they always suppress improvement, innovation, competition and good service.

Perhaps the most educational part of the articles and response from AARP members is the overriding emphasis placed upon age-related degeneration. The message is clear: resistance to living longer stems from expectations of loss of health and vigor. From the piece on the future of life extension science:

Perhaps most important of all: not everyone wants to live forever. "If you go out and interview a bunch of 90-year-olds, you don't find a whole lot that want to live another 50 years," says Richard Sprott, Ph.D., director of the Ellison Medical Foundation, which funds longevity research. "It's 50-year-olds who want to do that."

Then from the AARP discussion board for this special report - which I strongly recommend you read, by the way - we see this sort of sentiment, reinforced over and over again in many different voices:

I wouldn't mind living to 100+ if I could be physically independent and sel-sufficient and financially able to support myself.

...

The points made by both of you who have previously posted are well taken, and I definitely agree with them. I, too, would not want to live well beyond 100 only to find myself unable to care for myself, with no quality of life, and financially destitute.

However, since we're all thinking in terms here of something that has not yet been possible, we have to allow for the fact that, along with increased longevity, ways might be found to keep us healthy and productive for a much longer period of time. Suppose we could live beyone 100, but instead of being sick, frail, helpless and broke we were able to remain vibrant, healthy, and involved in working life much longer than people are now.

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I doubt there would be ANY demand for medicine or science to work on extending life if it is not healthy, productive life. Thus, I think we can safely exclude the thought that any studies would be done on keeping senile, incontinent, feeble people alive.

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I would love to live over 100 years, as long as I will be healthy. Then I could work for a living if I run out of money.

...

I would not mind living another 30 to 50 years, but only if I can support myself, keep working and busy (that's why I started my home business), remain healthy and stay active. I definitely would like to see my Son finish college, get married and watch his children grow. I would also like to travel the World with him as he competes in his sporting events and help him and his family in any way I can. I would not want to be put on life support or be placed in a nursing home. I would rather not be here if I could not be self-sufficient.

This is a topic I discuss on and off all the time, but it is an education to see it so much front, center and focus. One wonders if all the nonsense philosophy and navel-gazing bioethics floating around the healthy life extension community and the pro-death opposition is just so much smoke in the smokescreen. What average folk - those not paid to think deep thoughts and throw spanners in front of the real workers - care about are the by-products of youth and health: self-suffiency, the absence of suffering, a life of vigor and function. Which leads us to suppose that perhaps the Tithonus Error - the mistaken, often knee-jerk belief that a lengthening of life would mean more and greater disability - really is the main roadblock to greater widespread support for healthy life extension research.

Scientists may never be able to entirely deliver the Ganymede scenario of eternal youth, but they're working hard to ensure people avoid Tithonus' fate.

Abolish the vision of Tithonus in the minds of the many, and the road to the future of healthy life extension will open wide? Food for thought.

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Understanding Cancer Cell Metabolism
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Understanding key differences in cellular biochemistry now means the ability to build delivery mechanisms that can accurately target therapies to specific cell populations - such as cancerous cells. Here, scientists make progress in the biochemistry of cancer cell metabolism: the gene cyclin D1 "can dim the power production in the cell and in turn scale up its cancer-producing activities. ... From the cancer cell's point of view, the inhibition allows the cell to shift its biosynthetic priorities - it allows it to shift from making mitochondria themselves to synthesizing DNA and making the cell proliferate ... This discovery advances our understanding of the behavior of cancer cells and may suggest new types of cancer therapy ... We'd like to link that change in metabolism to therapies. We've been able to prove that we can see changes in metabolism in the [tumor], and we should be able to target that change and kill the cancerous cells."

Link: http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-69701.html

Nearly Getting the Picture
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The tenor of the more educated pro-death op-eds is changing, as illustrated by this piece in the Times Online. Authors are finding it harder to deny the plausibility of healthy life extension science, more or less steer their way around the Tithonus Error, and demonstrate whistful longing amidst the still-flaky justifications for standing aside and permitting untold billions of avoidable deaths. People fear the degeneration and powerlessness of aging; if that can be avoided, who would not choose to live longer? "If, however, science could offer us not just long life but long-drawn-out youth and health as well, if life extension were in effect youth extension and if the passing decades hardly touched us, perhaps one would answer the question differently. If one could be as youthful and fit at 90 as one was at 30, wouldn't one immediately grab the pills and swallow them? I wonder." Healthy life extension will be youth extension: given that age is no more than an accumulation of damage, and the best solution is to repair and prevent that damage, any progress towards longer life is progress towards longer youth.

Link: http://www.timesonline.co.uk/article/0,,2088-2340456,00.html

On Gene Expression and Aging
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Chris Patil of Ouroboros makes a good point while discussing a study of changes in gene expression in the aging liver: "A question unasked and therefore unanswered in this and many papers is what, if anything, age-related changes in gene expression signify: Are they deleterious, protective, passive responses to damage-induced signals, neutral, or other? It's a gigantic question, far beyond the scope of any one paper." I recall that Aubrey de Grey has suggested that we should fix or prevent all such changes in the course of a full-on attack on the aging process (or at least those that remain after other issues have been dealt with). From where I stand, it's an open question as to whether biotechnology - and the implementation timeline for specific improvements to healthy life extension medicine - will advance in a way that makes that approach more or less practical than identifying and fixing changes that are root causes of further problems.

Link: http://ouroboros.wordpress.com/2006/09/01/translational-control-of-transcriptional-control-in-the-aging-liver/

Medical Value, Despite Many Obstacles
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People spend more on medicine because advancing technology creates more and better options for improving life and health. On the ball and chain side, government intervention enables people to profligately spend money that is not their own - at least until the rationing kicks in. Government regulation raises the costs of medicine with no matching gain in quality or effectiveness. Despite the immense damage done through politics and short term greed, gains are still worth it in pure utilitarian terms: researchers "estimated that from birth, the increased life expectancy since 1960 -- approximately seven years, from 69.90 to 76.87 years - has cost $19,900 per added year of life. ... Comparing this $19,900 against the value of a year of life as defined by insurance companies and medical decision-makers - a figure that ranges from $50,000 to $200,000, according to different statistical estimates - [the researchers] judged the increase in medical costs to be a good value. ... By contrast, persons age 65 and older have increased their longevity by just 3.5 years since 1960, with a cost of $84,700 for each year of added life."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=50890

Targeting Via RNAi Manipulation
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Since I've previously discussed progress towards RNA interference (RNAi) therapies - more than once - and the way in which the future of medicine is all about better targeting, it seems appropriate to point out an advance that improves technology in both areas in one stroke. From the MIT Technology Review:

The main obstacles to using RNA interference to combat diseases, says John Rossi, chairman and professor of molecular biology at the Beckman Research Institute in Duarte, California, are ensuring that the RNA is taken up by the targeted cells so that it can do its work and that it is directed only at a tumor or a diseased area.

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The Duke researchers' innovation was to design a region on the RNA itself that directs the therapy to the malignant cells. This directing region is called an aptamer, a section of RNA selected from a large pool of candidates for its ability to bind strongly to a particular molecule -- in this case, a protein that appears on the surface of some prostate cancer cells.

...

After the Duke RNA binds its target on the surface of prostate cancer cells, it is eventually dragged inside the cell. Once inside, the RNA is cleaved in two by a protein native to the cell, freeing the gene-silencing region to find and guide the destruction of its target. RNA interference leads to the destruction of the intermediary between DNA and proteins, called messenger RNA. The Duke therapy destroys the messenger for a gene whose protein prevents prostate cancer cells from dying, even when outside signals tell the cells to do so. With this protection removed, cancer cells died.

Very clever. In addition, it has the look of being more cost-effective to deploy than other targeting strategies, at least at the present time. Comparable strategies - such as those using nanoparticles or that attach theraputic agents to antibodies or other molecules - require additional steps and materials to be prepared.

The Duke RNA therapy can be made in one step, moves through tissue easily, and could in principle be designed to target any cell in the body

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The Coalition to Extend Life
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This one was noted by the busy bees of the Immortality Institute: a lobbying effort for funding the attainment of physical immortality. (As opposed to, say, big-tent "politics of the practical" lobbying efforts to fund very modest gains of a few years, or avoiding the lobbying path altogether in favor of philanthropic funding). As for the Immortality Institute's positioning and message, the Coalition is all the way out there as suitable outrageous extreme. Plausible extremes backed by science tend to push the boundaries of more commonplace debate.

The tactic of advocating and publicizing technologically plausible extremes in radical life extension has been working pretty well in the past few years. The level and content of discussion of healthy life extension in the mainstream has indeed been greatly improved - and this feeds back to advocacy and basic research by way of increased support and funding for real anti-aging science.

As for all such things, it's rather hard to tell how much effort is behind it from the website, but that portion of the job is well done. The messaging is good. I can't say as I support the whole big government, tax dollar, work the system, public funding thing - but as always, live the life you want to live and work to the future in the way you see as best. In that respect, it's rather ironic that the Coalition to Extend Life message starts with a quote from Thoreau:

The great American author, Henry David Thoreau, wrote, "Time is but the stream I go fishing in." All of us enter that stream at birth and for a period of years we float along in different directions; experience joys and sorrows; taste the fruits that life has to offer and, inevitably, one day the water disappears and suddenly we no longer exist. Death has arrived and our short time on earth has expired.

As for the rest, I am happy to see more folk talking well and earnestly on the topic of radical life extension, physical immortality and the defeat of age-related degeneration:

As cognizant human beings we know that heretofore all people have reached a point where they die. This existential truth weaves its' way thru art, philosophy, religion, medicine, science, and other intellectual undertakings that attempt to understand our existence. Over the course of history there have been attempts to cure the insidious disease of aging but no "Fountain of Youth" has been found to halt the inevitable disintegration for our body, and its' ultimate demise.

Death is a mystery that is hard to comprehend. Like any mystery, though, it can be solved. In laboratories all over this world scientists are beginning to explain why cells age and die and how they can be rejuvenated. Breakthroughs on the biochemical processes that cause aging allow us to achieve immortality. The Coalition to Extend Life is dedicated to combating aging and promoting immortality for all. The struggle will not be easy. Immortality will change how we look at the world, and quite frankly many people fear new ideas and will vehemently oppose the radical transformation that will occur. Therefore, it is necessary to begin now!

I decided to start this organization because I do not look forward to death. I hope you feel the same way. Obviously, this is an idealistic goal but when you consider the alternatives, it makes a great deal of sense to fight for your dream, especially since it is within your grasp.

I sincerely hope you will be an active member of C.E.L. Together we can build a movement and create a society in which people can live indefinitely.

I am dedicating my life to this cause since I am not getting any younger; and neither are you.

Quite.

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More On Korean Research Timelines
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The Korea Times provides more on projected timelines for stem cell research in that country: "Cheju National University plans to set up a large biology research center with the aim of starting to use human embryonic stem cells in actual therapy around 2012. ... We recruited [Park Se-pill] as the head of the stem cell center to be established at our university, and seek to hire about 20 more researchers and experts ... We will focus on coming up with ways of differentiating stem cells into specific cells, a must to take advantage of embryonic cells for clinical purposes. The first target will be hard-to-cure diseases caused by nerve cell disorders as scientists are continuing to make breakthroughs in the field."

Link: http://times.hankooki.com/lpage/200609/kt2006090118134310220.htm

American Academy of Nanomedicine
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Via Nanodot, a link to the American Academy of Nanomedicine, "a professional, academic and medical society dedicated to advancing research in nanomedicine." The Academy publishes the Nanomedicine journal; you'll find a range of most interesting medical science within the latest issue: "First, we describe naturally occurring DNA repair nanomachines, using as an example the nanomachine that executes the nonhomologous end-joining (NHEJ) reaction for DNA double-strand break (DSB) repair. Second, we discuss therapeutic benefits that may be derived from the ability to modify the behavior of naturally occurring nanomachines, using as an example the concept of delaying DSB repair in rapidly dividing cancer cells to increase their natural sensitivity to radiation therapy. Third, we discuss similarities in the overall size, shape, and design of different nanomachines that manipulate DNA and RNA, and the possibility of developing nanomachines with new specificities not found in nature." Engineering better DNA repair would be a very big deal.

Link: http://www.aananomed.org/