As I noted a little while ago, the SAGE Crossroads website rose from the dead this year to restart its series of podcasts on aging research and longevity science, with a focus on policy matters and publicly funded research. That slant isn't quite my cup of tea, but each to their own. The most recent four podcasts are themed on economics:

What do the current economic models say about longevity?

KYLE JENSEN: The audience of the SAGE Crossroads website is made up of scientists, policy makers, and curious consumers. If there is one last statement you would like to make to them regarding the economics and longevity science in the future, what would it be?

ROBERT FOGEL: Don’t be afraid of it; it’s actually the leading industry. The demands of healthcare are going to pull all other industries forward. Of course they require new technologies in steel and heavy industry and as well as delivery systems. I think they should be looked at positively. Again I say if this were a privatized system, we would all say “gee it’s wonderful. All these people want more health care, this industry is thriving”. Let me put one other analogy. Suppose we made cars a government entitlement. Instead of cheering when auto production went up, we’d say, “Oh my God, we can’t afford this!”. How you finance it may greatly affect the psychology and actually the freedom of the economy to take advantage of these new opportunities.

Which is interesting, as this fellow spends the rest of his talk telling us that government entitlements are great and can always be fixed if they're not. "Fixed" is a word that springs to mind, yes, but not in the sense of "repaired."

How does longevity science contribute to the economy?

KYLE JENSEN: Mr. Perry, how have developments in aging research, longevity science, and public health affected the ways that Americans live the 65 plus years of their life?

DANIEL PERRY: Well, we are probably too close to the changes to appreciate them and to understand them, but we’ve really succeeded in scrambling the images of life’s mileposts of aging. We’ve added 50% to average life expectancy in the last 100 years, and all of the studies suggest that people are not only living longer, but they are living with less disability and they are healthier than any other time we have known in the past. The short hand for this is to say that 50 is the new 30 or that 65 and 70 are still the prime years of life, and I wouldn’t be a bit surprised if we were going to be saying that 85 is the new 60 before very long. In fact, at age 65, which at one point most Americans considered the beginning of the end if you will, most Americans can count on living another 18 years of life, and half of them will live past 90. All of this has had huge positive economic impact. The vast majority of people at middle age are now saying in surveys that they expect to work well past retirement age, traditional retirement age, half expect to work into their 70s, either because they need to or because they want to stay working and engaged.

Measuring the economic benefits of medical research and longevity science

KYLE JENSEN: Your work also seems to argue that longer, healthier life is very valuable yet historically undervalued and conservative. Why do you believe this is true?

DAVID MELTZER: Well, so the way I like to think of it is in terms of length of life and quality of life. So a lot of work in medical cost effective analysis and in other areas have tried to determine the gains to health in terms of both length of life and quality of life. You then weigh those gains versus the costs of the interventions that produce them. What my work is focused on, or at least an aspect of my work, is understanding how extensions of life create costs in ways that may not be obvious. So, for example, when you live longer, you have more years in which you have to support the cost of being alive, medical expenditures. Conversely, if you're living longer and working, you take earnings away from that. It's traditionally been the case that fields of medical cost effective analysis haven't included costs of living longer. As a result, cost effectiveness has also systematically underestimated the costs of life extending interventions. In contrasts, interventions that improve the quality of life don't have these costs due to length of life. As a result, there has tended to be a bias in traditional methods of cost effective analyses. You spend too much money on things that make you live longer relative to things that improve the quality of life. And that's been one of the major focuses in the work that I've done on cost effectiveness.

This way of looking at things is very much a function of the limited medical technology of today. When you can ensure increased longevity with accompanying extension of health - which is very much not the focus of mainstream aging and late-life disease research today - economic problems go away. Daniel Perry has it right: a healthy, working person at any age is a net producer of wealth. The more healthy people that exist, and the longer they live, the more wealth is produced.

Trying to find any economic benefit or trade-off in loss of function and aging to death is a form of the broken window fallacy. Destruction is always, exactly, and only destruction - there is no gain that comes from it.

Why living longer can only be beneficial to society

KYLE JENSEN: Do you feel that Americans that are living longer would impact social security, Medicare, and various other entitlement fields negatively?

GREGORY STOCK: Well, they certainly should impact those programs. The question is that these kinds of programs which always come up in these kinds of discussions are set up so that people when they are no longer functional and vital are able to be supported in some way by society, so if you have much, much older people chronologically that can be fully active and participate in society, then they should have to do that or should have to provide for themselves. And, you know, the other point of it is that something like social security is already going to be bankrupt, so of course if you have people living longer and you don’t make any adjustments and you try to support a large segment of the population that isn’t going to be a good solution.

KYLE JENSEN: Do you think we are on the right track to revamp those programs?

GREGORY STOCK: I don’t think we’re doing much at all, but those things will clearly occur and the political process will allow them to occur and will force them to occur when there is a real problem that is proximate rather than some real distant thing that can be passed off or left to the next generation or to later politicians.

Radical change is certainly ahead, as the present culture of entitlements and forced wealth transfer is barely sustainable even without the near future technologies of healthy life extension. Something has to give, and the longer the present political system lasts, the worse off we'll all be.

Posted by Reason at 2:04 PM
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I notice that two good review papers on the topic of stem cells, stem cell niches and aging are presently freely available in the latest Aging Cell. Journal publishers tend to put out these free full text promotions for a limited time, so take a look while the looking is there.

Stem Cell Review Series: Aging of the skeletal muscle stem cell niche

Declining stem cell function during aging contributes to impaired tissue function. Muscle-specific stem cells ('satellite cells') are responsible for generating new muscle in response to injury in the adult. However, aged muscle displays a significant reduction in regenerative abilities and an increased susceptibility to age-related pathologies. This review describes components of the satellite cell niche and addresses how age-related changes in these components impinge on satellite cell function.

You can find more about satellite cells and the aging stem cell niche back in the Fight Aging! archives as well. Just follow those links.

Stem Cell Review Series: Regulating highly potent stem cells in aging: environmental influences on plasticity

Significant advances in the past decade have revealed that a large number of highly plastic stem cells are maintained in humans through adulthood and are present even in older adults. These findings are notable in light of the reduced capacity for repair and regeneration in older tissues. The apparent dichotomy can be reconciled through an appreciation of the age-associated changes in the microenvironmental pathways that govern adult stem cell plasticity and differentiation patterns.

As this second paper illustrates, the weight of evidence is shifting to the view that we are packed full of functional stem cells even as we age. These stem cell populations are shut down by changes in biochemical signals and systems, possibly due to accumulated damage that causes aging and malfunction, possibly as an evolved defense against the increasing likelihood of cancer in old tissue. As cancer medicine becomes increasingly sophisticated, safe and effective, learning the signals to set our stem cells back to work begins to look like a plausible near term strategy for enhancing longevity.

Posted by Reason at 9:47 AM
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A timely piece in Wired today:

Gandhi once said, describing his critics, "First they ignore you, then they laugh at you, then they fight you, then you win."

After declaring, essentially out of nowhere, that he had a program to end the disease of aging, renegade biogerontologist Aubrey de Grey knows how the first three steps of Gandhi's progression feel. Now he's focused on the fourth.

"I've been at Gandhi stage three for maybe a couple of years," de Grey said. "If you're trying to make waves, certainly in science, there's a lot of people who are going to have insufficient vision to bother to understand what you're trying to say."

This weekend, his organization, The Methuselah Foundation, is sponsoring its first U.S. conference on the emerging interdisciplinary field that de Grey has helped kick start. (Its first day, Friday, will be free and open to the public.) The conference, Aging: The Disease - The Cure - The Implications, held at UCLA, is an indication of how far de Grey has come in mainstreaming his ideas.

The Methuselah Foundation's research is beginning to produce results:

In research that will first be presented on Friday at the conference, Methuselah-funded scientists will demonstrate a proof-of-concept experiment for using bacterial enzymes to fight atherosclerosis, or the hardening of the arteries. That's an idea that de Grey has been pushing for years.

The signs continue to be promising for the Methuselah Foundation to be the boulder that leads the avalanche, gathering legitimacy and researchers to the task of repairing aging at an accelerating rate. Those folk who helped to get this initiative off the ground back in 2004 should be feeling pretty pleased right about now.

Posted by Reason at 12:51 PM
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Hair loses its color with age due to a decline in activity of melanocyte pigment-producing cells, likely another symptom of the general fading of stem cell populations throughout the body. A recent paper adds evidence for that view:

Hair graying is one of the prototypical signs of human aging, but its mechanism is largely unknown. To elucidate the mechanism of hair graying, we investigated gene expression related to melanogenesis in human hair.

The key molecules in melanogenesis, microphthalmia-associated transcription factor-M (MITF-M), Sox10, Pax3, tyrosine related protein-1 (TRP-1), and tyrosinase, were absent or greatly reduced in the bulbs of white hair compared to black hair.

Melanocyte stem cells (MSCs) or melanocytes express markers for neural crest cells, Sox10, Pax3, and MITF-M. Taken together, our data suggest that hair graying is caused by defective migration of MSCs into the bulb area of hair.

Setting any given group of aging stem cells back to work by introducing appropriate biochemical signals - or cloning many more stem cells to reintroduce into the body - are very plausible projects for the decade ahead. Either could greatly improve the immediate situation, and the second strategy has already been demonstrated in heart therapies. I can envisage cloning and reintroduction of massive numbers of melanocytes as a clinical method to reverse hair graying in the late 2010s.

Risk of cancer is the challenge to all these attempts to put stem cells back to work in the aging body. That risk is why evolution has left us with stem cell populations that decline in old age, as damage to cells and biological systems is accumulating. Introducing cloned stem cells seems pretty safe, based on the evidence to date, but turning stem cells back on through the use of biochemical signals is much more of an unknown. This challenge will be overcome, but it's yet more of an incentive to address the fundamental issue of age-related biochemical damage rather than patching issues one by one.

Posted by Reason at 2:00 PM
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We know that calorie restriction slows the accumulation of nuclear DNA damage - possibly by enhancing DNA repair mechanisms - just as it slows more or less every other age-related change of interest that scientists have investigated. The degree to which ongoing random damage to nuclear DNA contributes to degenerative aging is debated, however:

A paper by Aubrey de Grey outlines his view of nuclear DNA damage and aging: "Since Szilard's seminal 1959 article, the role of accumulating nuclear DNA (nDNA) damage - whether as mutations, i.e. changes to sequence, or as epimutations, i.e. adventitious but persistent alterations to methylation and other decorations of nDNA and histones - has been widely touted as likely to contribute substantially to the aging process throughout the animal kingdom. Such damage certainly accumulates with age and is central to one of the most prevalent age-related causes of death in mammals, namely cancer. However, its role in contributing to the rates of other aspects of aging is less clear. Here I argue that, in animals prone to cancer, evolutionary pressure to postpone cancer will drive the fidelity of nDNA maintenance and repair to a level greatly exceeding that needed to prevent nDNA damage from reaching levels during a normal lifetime that are pathogenic other than via cancer or, possibly, apoptosis resistance." In other words, beyond sufficient work to prevent cancer, we don't need to repair nuclear DNA over a human lifetime. Maybe. This debate is ongoing; there are many others who argue that DNA damage is an important root cause of aging.

A paper caught my eye today - a comparison in mice of the effects of calorie restriction versus Ames dwarfism on nuclear DNA damage. Both extend life, and both reduce DNA damage:

Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis [i.e. Ames dwarfism] significantly increase life span in the mouse and reduce multiple symptoms of aging, including cancer.

To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line harboring multiple copies of the lacZ mutation reporter gene as part of a plasmid that can be recovered from tissues and organs into Escherichia coli to measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf.

While both CR wild-type and ad lib dwarf mice lived significantly longer than the ad lib wild-type mice, under CR conditions dwarf mice did not live any longer than ad lib wild-type mice. While this may be due to an as yet unknown adverse effect of the C57BL/6J background, it did not prevent an effect on spontaneous mutation frequencies at the lacZ locus, which were assessed in liver, kidney and small intestine of 7- and 15-month-old mice of all four cohorts.

A lower mutant frequency in the ad lib dwarf background was observed in liver and kidney at 7 and 15 months of age and in small intestine at 15 months of age as compared to the ad lib wild-type. CR also significantly reduced spontaneous mutant frequency in kidney and small intestine, but not in liver. In a separate cohort of lacZ-C57BL/6J mice CR was also found to significantly reduce spontaneous mutant frequency in liver and small intestine, across three age levels. These results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR.

Or it may be any of the many other line items of age-related degeneration resisted by both CR and Ames dwarfism. The present trouble with debates on the contribution of nuclear DNA damage to aging is the lack of any good demonstration of extended life (or no extension to life) through prevention of mutational damage only. There are too many confounding factors.

Posted by Reason at 2:40 PM
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The methuselah gene in fruit flies, which when expressed gives rise to the methuselah cell receptor (or mth), has been known for a decade now. It is one of a small number of single gene manipulations which can meaningfully extend longevity in this species - by 35% in this case.

When it comes to figuring out what's going on under the hood, even single gene manipulations in small creatures are terribly, enormously complex. This is one of the many truths that leads those researchers who focus on genetic and metabolic engineering to say that any significant extension of human life span through these methods is far in the future. It's a huge, huge undertaking, from our present position, to consider engineering any form of significant change to the way in which our metabolism works.

(Which is why I support far less complex and more certain approaches aimed at repairing the metabolism we have. The mountain of metabolic complexity is there, climb it if you must, but to get to the valley of enhanced longevity on the other side in good time, then use the level road of damage repair strategies that winds around the mountain's base).

You should take a look at a recent PLoS ONE paper on the methuselah gene for an impression of the complexity involved, as well as for a longevity gene in action in wild populations, where it varies from group to group and between individuals:

Williams' theory of antagonistic pleiotropy describes how pleiotropic alleles that increase fitness early in life may experience positive selection even though they incur a fitness cost later in life. Identified aging genes have consistently shown costs to lifespan extension, particularly in reproduction. Although there is some evidence that lifespan and reproductive success can be decoupled, multiple analyses have revealed previously undetected tradeoffs under specific conditions.

In addition to demonstrating negative effects on reproduction, longevity mutations are positively correlated with stress resistance. Such correlations may explain aspects of lifespan evolution, and why loss-of-function mutants can result in lifespan extension. However, it remains unclear whether identified aging genes are major contributing factors to the genetic variance for longevity that is routinely observed in populations.

The researchers then provide a good slab of evidence for variations in the methuselah gene to contribute to observed variations in longevity in wild fly populations. It makes sense for any successful species to have central controlling points in their biochemistry for such things as energy devoted to reproduction, stress resistance, longevity and so forth. Varied abilities across generations and individuals means a species more able to populate new habitats and survive environmental changes that favor one set of abilities over another - so we'll see more of that versus any other alterative biochemical arrangement.

The 30-50% range keeps coming up in experiments to extend life span in small mammals and flies; a number of different ways of achieving this degree of success have been demonstrated in the past 20 years. It seems that this is the natural plasticity of longevity for the biochemistry of many complex species. In some cases, it can be achieved by signficant changes in diet alone, while in others a change to one or a couple of genes is needed - a small change from the point of view of evolution. For the reasons given above, I suspect that this plasticity is a feature of most successful species, a buffer against change inherited from the ancestral past.

Posted by Reason at 4:14 PM
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You have to look hard in the scientific literature to find evidence of any age-related changes made worse by the practice of calorie restriction - the only one that springs to mind right now is that progression of ALS is likely to be worsened. The much more common story is that detrimental change is resisted or attenuated: immune system aging, stem cell decline, heart aging, DNA damage, loss of health, loss of vitality, increase in risk of age-related disease ... all slowed by simply eating less while still obtaining optimal levels of nutrients. Almost everything studied by reserchers to date shows strong evidence of being made better through calorie restriction as a lifestyle choice.

Now we can add sarcopenia, age-related muscle loss, to this long list. That is counterintuitive - eating more leading to losing more muscle mass over the years - but then what is straightforward and simple in biology? Here's the abstract at PubMed:

Sarcopenia, the loss of muscle mass with normal aging, devastates quality of life - and related healthcare expenditures are enormous. The prevention or attenuation of sarcopenia would be an important medical advance.

Dietary restriction (DR) is the only dietary intervention that consistently extends median and maximum life span, as well as health span in rodents. Evidence suggests that DR will have a similar effect in primates. Furthermore, DR opposes sarcopenia in rodents.

We tested the hypothesis that DR will reduce age-related sarcopenia in a nonhuman primate. Thirty adult male rhesus monkeys, half fed a normal calorie intake and half reduced by 30% in caloric intake, were examined over 17 years for changes in [muscle mass]. Body weight-adjusted skeletal muscle mass declined somewhat in both groups but was far more rapid in the control group. We have shown that moderate, adult-onset DR can attenuate sarcopenia in a nonhuman primate model.

That would seem to shoot down the sarcopenia as dietary issue theory, in which the lower-protein diets of the elderly are supposed to cause problems. In fact, those diets should be protective, if this calorie restriction connection follows through to humans. You might also look back at evidence suggesting that sarcopenia stems from one obscure but important biochemical process becoming slowly less efficient, and that leucine supplementation from middle age onwards may reverse this growing inefficiency.

For my money, in advance of further research, I suspect that the stem cell connection is the easy answer. If calorie restriction slows the decline in stem cell activity, then the normal ongoing turnover in muscle tissue should be more readily maintained. We shall see what the real answer is in due course, but practicing calorie restriction in the meantime is still the smart thing to do.

Posted by Reason at 3:52 PM
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You have a great deal of control over the course of your future health: how healthy you're likely to be, and how long you're likely to live. The unexpected always happens, but you can greatly influence the odds. Your actions over the years can move your life span across decades, just through simple lifestyle choices and good health practices, and even without the expected advances in medicine that lie ahead. An illustration:

A Finnish study of identical twins has found that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy. The findings suggest that lifestyle, more than heredity, contributes to insulin resistance in people who are obese. Insulin resistance increases the chance of developing diabetes and heart disease.

And more:

Here's some very good news: your genes are not your destiny. Earlier this week, my colleagues and I published the first study showing that improved nutrition, stress management techniques, walking, and psychosocial support actually changed the expression of over 500 genes.

Taking up exercise and a sane diet rapidly changes the way your body operates at the cellular level, and for the better. The body is a complex machine of regulated processes, interactions and feedback loops, and like all machinery, it will fail and malfunction more rapidly if run poorly and without maintenance.

Amazing medical technologies will arrive in the next few decades, with the promise of repairing the biochemical damage of aging and rejuvenating the old. The more you run yourself down, however, the lower your chances of living to benefit from the future of longevity medicine. Why risk it?

Posted by Reason at 4:54 PM
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By way of a reminder, the Aging 2008 symposium will be held later this month, on June 27th at UCLA, Los Angeles. It's a free event for the public, organized by the Methuselah Foundation, and attended by many of the movers and shakers in aging science and advocacy for longevity research:

Applying the new technologies of regenerative and genetic medicine, the engineering approach to aging promises to dramatically extend healthy human life within the next few decades.

How do you and your loved ones stand to benefit from the coming biomedical revolution? Are you prepared? Is society prepared?

At Aging 2008 you will engage with top scientists and advocates as they present their findings and advice, and learn what you can do to help accelerate progress towards a cure for the disease and suffering of aging.

The symposium leads into the Understanding Aging scientific conference, an extension of the Strategies for Engineered Negligible Senescence conference series of past years. These events are a necessary part of establishing a research community sufficiently large and well-organized to make significant progress in longevity science. We'll be seeing more of this sort of thing in the years ahead: connections made, minds changed, notes swapped, science moved forward.

Posted by Reason at 3:57 PM
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Many species of animal age very slowly, and some so slowly that researchers have not yet been able to pin down either a rate of aging or a life span absent predation and accident. Some of those species might not age at all, but we'll have to wait for researchers to establish whether or not this is the case. Take the lobster, for example. Despite all the eating and farming that takes place, there's less funding for basic research into lobster biology than you might expect. As a consequence:

To date, there is no proven method to determine the exact age of a lobster. ... as best scientists can tell, lobsters age so gracefully they show no measurable signs of aging: no loss of appetite, no change in metabolism, no loss of reproductive urge or ability, no decline in strength or health.

Lobsters, when they die, seem to die from external causes. They get fished by humans, eaten by seals, wasted by parasites, but they don't seem to die from within. Of course, no one really knows how the average lobster dies. There are no definitive studies.

Turning to another common sea creature, species of sea urchin appear to be in the same boat as the lobster: if they're aging, they're doing it very slowly.

The red sea urchin Strongylocentrotus franciscanus is a long-lived species and may live in excess of 100 years based on tagging studies in the field and corroboration from radiocarbon analyses as reported in the literature. Size-specific survival estimates reported here show no change in annual survival probability across the 6 largest 0.5cm size classes from 14.6 to 18.1cm. In addition to no change in survival probability there is no reduction in reproductive capacity with size. Red sea urchins show no evidence of senescence and so do not fit well within the context of the disposable soma theory of the evolution of longevity.

You'll recall that a baseline definition for aging is an increase in mortality rate with time, which doesn't happen for these urchins, or at least to any degree that can be detected via study methods at the present level of funding. This presents a challenge for the classic interpretation of the evolution of aging, which suggests that putting more resources towards tissue repair and the upkeep of biological systems that can support extended life spans is a losing proposition. Evolution favors the quick win, a fast and efficient organism that can reproduce quickly - and rapidly fall apart afterwards.

Or so the thinking goes. Clearly, extremely long-lived and possibly ageless species did evolve, so theory must be extended. The latest thinking on the matter theorizes that crowding can lead to a runaway evolutionary competition for longer lives, an arms-race for the biology that lets you wait out the competition for limited space:

adults live in crowded but stable conditions in which new opportunities for maturation arise rarely. In such situations, it behooves an individual organism to outlive its neighbors, so that when they die its seedlings or larvae have a place to dig in and grow up.

Does the humble urchin have any relevance to the future of human aging and longevity medicine? Not directly, I'd imagine, in the sense of applying learned science. But as more people understand the range of what is possible in living organisms, support for engineering a better healthy life span in our species will grow, whether or not that goal is achieved by mining nature for new metabolic biotechnology.

Posted by Reason at 1:23 PM
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There's nothing wrong with becoming old, but everything wrong with aging. Old means experienced, invested, wealthier, time-tested and just all-round better for having been around the block. Aging, on the other hand, is the direct result of biochemical damage you picked up along the way - ongoing deterioration that is a side-effect of being alive. The passage of years brings a constant flow of opportunities for growth and self-improvement, until aging takes away your ability to compete, your ability to take care of yourself, and eventually your life. Someone should look into that.

If you're not one to think much about medical research, you might be under the impression that aging is fairly mysterious, a primal and inevitably metered process quite separate from the diseases of old age. In fact that's not the case. Aging is exactly and precisely the root cause of those diseases of old age, and scientists have a good understanding of what aging actually is, once you get under the hood and start looking at cells and the cellular environment:

• Loss of important cells without replacement over the years
• Accumulation of damaged, malfunctioning and senescent cells
• Free radical damage resulting from damaged mitochondrial DNA
• Accumulation of waste chemicals that cannot be broken down inside cells
• Accumulation of biochemicals gummed together by sugar outside cells
• Formation of amyloid deposits throughout the body
• Breakdown of cell control processes, leading to the runaway growth of cancer

The short story is that aging is damage and change, rust and wear for our biology that is caused by the normal operation of human biochemistry. You can't run machinery without causing wear, and you can't run factories full of machinery without creating waste by-products. Machinery with a lot of rust and wear breaks down in any number of ways, and biological machinery is no exception - just a few classes of wear, rust and buildup of waste lead to a vast array of different malfunctions.

When you can't do anything about the rust, wear and waste, you put on the best face possible under the circumstances and soldier on. Perhaps you convince yourself that the miseries of an increasingly damaged body and mind are for the best. It's a slowly boiling pot, but it's our slowly boiling pot, and it's all we have. We humans are good at that sort of proactive self-deception for the sake of sanity in the face of the inevitable - we've been doing it for a very long time indeed.

All habits outlive their usefulness, however, and self-deception about aging has lingered past its time. These early years of the 21st century are the opening notes in a symphony of biotechnology, an expanding revolution in medicine, research and computation. The breadth and speed of research in modern biotechnology is breathtaking; already, the laboratories of of this decade are far beyond those of the 1990s:

• Cancer researchers are developing targeted, precise, safe cell destruction therapies that will applicable to any unwanted, damaging cells.

• Scientists are turning the immune system to destroy the amyloid buildup of Alzheimer's disease, and other amyloids of aging will follow.

• Methods to repair and replace damaged mitochondrial DNA are emerging from the laboratory.

• The regenerative medicine community is deciphering the genetic and chemical controls that will make our stem cells do our bidding, to replenish cells lost to age.

• Researchers are plundering the bacterial world for enzymes that can break down damaging biochemicals that build up with age.

If you think aging is inevitable, and that we should make the best of it, then you're probably not helping the world's researchers in their efforts to repair the damage that causes aging. You see, funding for research is very dependant on the zeitgeist of the age. If most people think that aging is inevitable, conservative funding bodies won't fund research aimed at the repair of biochemical damage that causes aging. Thus little progress occurs, no-one in the public is given any reason to doubt that aging is inevitable, and medicines to repair aging are pushed further into the future, perhaps out of reach for you and I.

Given the choice to be old, wise and better without being aged, frail and ill, wouldn't you choose to repair the damage? It's not a hypothetical question anymore, and the number of years it takes to develop medicines of repair for aging depends upon your answer.

Posted by Reason at 2:53 PM
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The rough estimate of resources required to develop - for mice - the medical capabilities called for by the Strategies for Engineered Negligible Senescence (SENS) is presently $1 billion over ten years, give or take.

Each of these [six lines of research] would require total funding in the range of $2m to $15m per year, spread over at least three and sometimes ~15 research teams. These teams will typically be working in a university or other research setting. [The lines of research] span six of the seven types of "damage" that Dr. de Grey has identified as the key intermediates in aging; the one not listed here is cell loss, whose rectification by stem cell and growth factor therapies is the subject of sufficient existing work worldwide.

That's for the whole spectrum of longevity therapies: engineering the body to make cancer impossible; replacing lost cells; ensuring mitochondrial DNA damage can no longer cause issues; destroying unwanted cells that cause damage; breaking down crosslinks and amyloid that gum up biochemistry; removing hard-to-degrade biochemicals in old cells. Given all that, you should be able to rejuvenate aged mice, and extend their healthy lives considerably. Then it's onto moving the technology to work for humans, where the cost really starts to rack up - but with the technology demonstrated in mice, there should be plenty of enthusiasm to pay that cost.

What does a billion dollars and ten years really look like when you're taking about warm bodies, concrete and conferences? It turns out to represent something like 500 researchers, plus resources for equipment, facilities and support staff, if you keep things lean and distributed, making the best use of existing research facilities and ongoing programs.

If you apply the 1:9:90 rule to a research community, you can expect that a 500-scientist strong group will include perhaps 5 researchers who are very respected and appear in the media in connection with their research, 50 who are well known in the field and very capable, and the remaining 445 ranging from research associates to skilled scientists yet to reach the heights of their careers. This community might take the form of ten dedicated laboratories at large universities, a few for-profit enterprises, and more than fifty significant initiatives within other large research organizations.

For comparison, that is considerably larger than the present calorie restriction research community but considerably smaller than either the cancer or Alzheimer's research community. Calorie restriction research and development is probably well over $1 billion in investment to date, but only if you count funds for trials and commercialization employed by companies like Sirtris; I would imagine that basic and animal research has consumed rather less than that.

At the present time, I would be surprised to find more than 50 scientists worldwide working to develop biotechnologies that would fit into SENS as-is. Outside the regenerative medicine and cell therapy community, that is. Clearly, there is a way to go for fundraising and other efforts to influence the direction of research in the broader scientific community.