I think that an important point is illustrated in a recent study on the relative cost and effectiveness of a good lifestyle versus drugs on age-related diabetes.

Compared with the placebo intervention, the lifestyle and metformin interventions were estimated to delay the development of type 2 diabetes by 11 and 3 years, respectively, and to reduce the absolute incidence of diabetes by 20% and 8%, respectively. The cumulative incidence of microvascular, neuropathic, and cardiovascular complications were reduced and survival was improved by 0.5 and 0.2 years. Compared with the placebo intervention, the cost per [quality-adjusted life-year (QALY)] was approximately $1100 for the lifestyle intervention and $31,300 for the metformin intervention. From a societal perspective, the interventions cost approximately $8800 and $29,900 per QALY, respectively. From both perspectives, the lifestyle intervention dominated the metformin intervention.

In other words, if you're not taking good care of yourself now, don't expect your future medical bills to be low. Even though the cost of medicine of a given effectiveness should decline with time - due to competition in the markeplace, increasing research into efficiency and effectiveness, improval of existing methodologies, and so forth - this trend could quite easily be offset by encroaching socialism in medicine.

Besides paying some of the highest prices for health care, we have the dubious distinction of having the most heavily regulated healthcare system in the world. In no other country on earth are doctors and hospitals subjected to as many oversight and enforcement agencies, bureaus and commissions. Rules, regulations, and laws are duplicated, redundant, multiplied, magnified, and contradictory. Laws and regulations covering doctors and hospitals plus all the other parts of our healthcare system now account for over half of all the words, sentences, and paragraphs in our entire body of law.

If regulations could make a healthcare system work better, ours would surely be perfect. In fact, the opposite has occurred. Even those who believe that only government regulation can assure quality health care should face this fact. More laws and regulations are not going to fix our system. If we are truly concerned about the high cost of health care, if we really desire greater safety and higher quality, then we must undertake a dispassionate analysis of the current mess. If we wish to begin effective treatment of our healthcare system, we must first make an accurate diagnosis.

The other main consequence of medical socialism (and other protectionist, centralization or entitlement programs) is that it may just be that the whole system will collapse in some way before you get to the point of needing expensive medicine - you'll think a lot more rationally about future costs in healthcare incurred today if you assume it likely you'll be paying in full.

You should not expect insurance or governments to pay for real anti-aging treatments when they become available. They might do it, or they might not. There are several proposed future scenarios under which the medical insurance industry and government programs are bankrupted or forced into reform by extended healthy life spans. "Forced into reform" is a polite euphemism for "we are not paying for your treatment." The power of compound interest allows you to accumulate a great deal of money before you will need to spend it on retirement and future medical technologies - so make best use of your time and save wisely.

The future is uncertain; you shouldn't count on advances in serious anti-aging medicine arriving in time to make your later life easier, healthier and longer. So look after your health, and raise your voice in support of serious anti-aging research and more effective medicine.

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More politics for those of you who like to keep an eye on such things; the current state-level battles in the US are likely to set the script for coming attempts to criminalize medical research by federal legislators. It's a strange world we live in, one in which groups of people fight so hard to prevent cures for age-related conditions from being realized.

The debate over embryonic stem cell research in Massachusetts has been getting a fair amount of press in past days. A summary of the pertinent points can be found at Newsweek:

From an academic standpoint, Massachusetts may have the most to lose if stem-cell research is outlawed or discouraged. "At this moment," says Boston-based state Sen. Cynthia Creem, "there are more scientists doing groundbreaking biological and medical research within 10 miles of my desk than in any other city in the world."

...

The governor, whose wife suffers from multiple sclerosis, a potential target of stem-cell research, had met with a prominent Harvard scientist and backed Creem's original bill. But Romney, a Republican rumored to have national political ambitions, stunned stem-cell supporters with a carefully crafted statement. Yes, he would support some forms of the research. But nuclear transfer performed on embryos created solely for research purposes—the most controversial and one of the most promising techniques—was out of the question.

Bioethicist Arthur Caplan dismantles the Govenor's position in his latest column:

In a state with an economy intimately linked to research in the life sciences, a pronouncement from the governor that the kind of stem cell research being aggressively pursued at world-class universities in California, Singapore, the United Kingdom, Israel, China, India and Korea ought not be done in the Commonwealth is going to receive a very cool reception in many quarters.

Meanwhile, funding and other legislative debates continue in Maryland and in Utah.

Being libertarian, I'm not in favor of state funding for anything; I am in favor of various layers of government getting out of the way - the real damage done so far to progress in stem cell research in the US has resulted from the threat of criminalization. This has scared away the vast pool of potential private funding and greatly slowed progress by those companies and new ventures best placed to move ahead with the commercialization of new research. Even now, federal anti-research legislation in the US is still a possibility - all the more reason to speak up in defense of curing age-related conditions through research into therapeutic cloning and embryonic stem cell research.

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Some thoughts to chew over for those of you with a political bent, found at the end of a fairly wonkish article at Newsweek:

For a country accustomed to leading the world in medical research, the loss of momentum for the biotech industry together with the human cost of the stalled research is prompting a fresh attempt at legislation on Capitol Hill. Republican Mike Castle of Delaware and Democrat Diana DeGette of Colorado are introducing the "Stem Cell Research Enhancement Act of 2005," which would allow federally funded researchers to use embryos that would otherwise be discarded by fertility clinics if patients agree to offer them for research. The lawmakers introduced the same bill last year and believed they had enough votes for passage.

Republican leader Tom DeLay refused to allow the bill to come to the floor for a vote, and he is playing the same game this time. The current bill has 156 cosponsors in the House and the support of such staunch Senate Republicans as Orrin Hatch of Utah. It would easily pass in both the House and Senate if it weren't for the stranglehold the right has on Bush and the GOP. If ever there was an issue where Democrats could borrow a page from Norquist's playbook and unite under a single winning banner, this is it.

Politicians only seem able to "fix" a problem of their own creation by piling it on higher and deeper. Politicians and other agents of the state cannot create - all they can do is obstruct and destroy. Meanwhile, private funding for research into curing age-related conditions continues to be deterred by the threat of criminalization. Meanwhile, millions continue to suffer and die.

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An interesting conversation regarding evidence of aging in bacteria previously thought to be essentially immortal is currently taking place on the Gerontology Research Group mailing list. Biogerontologist Aubrey de Grey had this to say on the topic:

Based on the evidence so far available, I think there is indeed a truly fundamental phenomenon being demonstrated here. It seems likely to me that all unicellular organisms that have cell walls (as opposed to only cell membranes) will behave much as shown in this study, because the cell wall is a heavily cross-linked proteinaceous structure within which accumulating damage does not diffuse (as it does in lipid membranes). If E. coli grow by adding more cell wall at the centre (which I think they do), therefore, increasingly old "poles" will indeed feature an increasing amount of damage (e.g. extra cross-linking and hardening). (Note that the authors' use of "pole" is possibly misleading, as that term normally applies to the tip of the mitotic or meiotic spindle, a structire not present in bacteria.) So in hindsight (presuming that the above turns out to be true), this is (just as Pete Estep said) a case where we fell too in love with the natural hypothesis in the absence of data. Rather like the inability of one mutation to extend lifespan, which Tom Johnson had such a hard time in getting the field to accept back in 1988. But note, it doesn't apply to animal cells, as they don't have cell walls. So a crucial thing to do is to repeat this experiment with single-celled animals.

...

It's probably the most talked-about scientific publication of the month, in fact. It's certainly very exciting, but various details need to be kept in mind at this stage:

1) The experiment was done for eight generations and showed a linear decline in the growth rate with increasing numbers of generations in which the old pole was inherited. This is in contrast to the standard pattern in aging where the functional decline accelerates with age. It is thus very important to extend this study to 20 or 30 generations to see whether the trend eventually accelerates or levels off. Of course the entire lineage does not need to be followed -- one just needs some cells at each point in the virtual lineage.

2) The authors measured "growth rate", and they really do mean rate of increase in the size of the cells. However, they note that new-pole daughters are larger on average than old-pole ones, and additionally that the new-pole daughter tends to divide first. The latter is to be expected, since increase of size is generally limiting for generation time for bacteria in rich medium. This merits a lot more discussion (for example there is nothing about whether multi-generation-old-pole cells are especially small), because the whole result may be because smaller cells grow more slowly at first (not that that wouldn't be interesting, of course). The authors describe the above results as showing that there is no "juvenile phase" whereby the new cell needs to go through some initial maturation process before it gets going, but they forget that it may be the daughter with the old pole that is going through such a phase.

3) The authors allude in the discussion to the phenomenon constituting a 2% "cost" of the aging process at the population level. They don't elaborate, but I think the meaning must be that the colony would grow 2% faster if all cells grew as fast as the new-pole ones. But this is not the right calculation if one wants to determine cost, because if the divisions were precisely symmetrical then the old-pole cell would grow faster but the new-pole cell would grow more slowly. I haven't done the maths but I strongly suspect that asymmetrical division (and hence asymmetrical dilution of damage) can for some examples of the function linking growth rate to damage levels confer a higher colony growth rate than symmetrical division.

4) Possibly the main reason the above points matter so much, especially the last one, is because of the effect on the validity of concluding that the observed phenomenon is universal, inescapable etc. There are numerous circumstances in which an organism's optimum metabolic tactics vary non-linearly with stress: for example the increase of maintenance at the expense of reproduction in caloric restriction, or the fusion response of mitochondria to high stress, or the senescence response of cells to over-frequent double-strand breaks. I suspect that under a variety of alternative, reasonable assumptions, the colony growth rate would switch from being best with symmetrical division to being best with asymmetrical division depending on whether stress (e.g. oxidative) and hence rate of damage accumulation was above or below some threshold. If so, repeating this experiment under low oxygen might give different results.

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Andrew Lynch pointed me to a New York Times article profiling Hans S. Keirstead; you may recall I've mentioned his research into curing paralysis using embryonic stem cells at the Longevity Meme.

Dr. Keirstead, an assistant professor at the University of California campus here, has been making paralyzed rats walk again, using a treatment based on human embryonic stem cells. Next year he and his corporate partner, Geron, plan to try treating people who have recent spinal cord injuries, in what would almost certainly be the first human trial of any therapy derived from such cells.

"You've got a patient community out there that is in desperate need," Dr. Keirstead said in an interview. "If the treatment is safe, let's get it out there and try it."

And to those who argue that it is too soon to test his technique on humans, he has an answer. "There will always be people who say slow down, slow down," he said. "I guarantee you none of them have relatives in wheelchairs."

Human nature being what it is, we see the same thing happening for research into healthy life extension and cures for age-related degenerative conditions. The folks standing in opposition aren't the ones suffering...

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I recently mentioned a little of the upside relating to public discussions of biological immortality (a state of agelessness, not invulnerability) - this in connection to the "suitable outrageous extreme." In essence, the presence of a serious discussion about the science of a cure for aging and a post-aging world creates an environment in which is is easier to gain support and raise funding for more modest research into extending the healthy human life span. This more modest research still happens to be the first step on the road to a cure for aging. Talking about the end goal speeds the journey by increasing public acceptance and thus driving funding. In that sense, I'm all for the responsible discussion of biological immortality through medical technology - curing aging, in other words. On the other hand, talking about immortality rubs some intelligent, well-meaning folks the wrong way right off the bat. Two good examples are here:

• Modern Day Alchemists
• Modern Day Alchemists, Part II

We can see that this fellow is so repulsed by something that is "obviously" fringe that he throws out or refuses to investigate associated facts and science - despite coming across as someone who would be sympathetic to a more subtle approach. For example:

To these concerns, de Grey would no doubt say, "Don't give me possible problems that might or might not happen. Give me the possibility of problems that might or might not be so bad that it's preferable to carry on condemning 100,000 people a day to death, forever."

If there's one thing I hate more than brute force, it's brute reasoning. I wonder how many of those people die from war, famine, car accidents, political prosecution, disease or other factors a genetic code for immortality wouldn't solve. Come to think of it, how are we supposed to get the secret of immortality to people who can't even get clean water? Or how are we going to stop wars? Sure doesn't look like finding immortality is going to do a lot to reduce that amazingly large questionably calculated number.

A few moments of research would uncover that, yes, approximately 100,000 people each and every day could be saved by a cure for aging and age-related degeneration. Another 50,000 each day die from violence, non-age-related disease such as malaria, and other consequences of politically-imposed poverty - but you can't hold back progress on account of poor distribution strategies and bad politics. That's simply reaching for all the old, disproved arguments against any new technology. A rising tide raises all boats, and the building of better boats is a separate topic from raising the tide.

There's much more in that and similar veins of course, the sort of thing an educated person would pick up from filtering the public opinions of scientists and a little knowledge of science through a prexisting bias that any talk of a cure for aging is "fringe" or "cultish." The question would be what we advocates can take away from this view point. What can we learn? From my observations, this sort of reaction is in a minority compared to more positive responses - especially when balanced against the "outrageous extreme" effect of a discussion of immortality on public support for near-term healthy life extension goals. Still, is there a good way to gain the support of people like this while continuing to educate the public about the possibilities offered by healthy life extension research and the fight to defeat aging?

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Jay Fox weighs in on social security and age-related frailty:

Can this be avoided? Ironically, people who oppose life extension technology - i.e., people who claim to value the dignity of human life and of our elders - are the very people who may ensure that this collapse arrives. People who oppose life extension and medical research are in fact going to cause frail people to overburden society to collapse. Needless to say, society will not go down without a fight, and frail people are the ones who will suffer at the hands of the disenfranchised young.

If you truly care about our elders, you owe it to them to make sure that we find a way to prevent the crisis of the impending tsunami of frail people that will flood society in the next 50 years. You owe it to them to find a way to make frailty the exception among the extremely old, rather than the rule.

I've had my say on this before; quite aside from pointing out that all these "problems" could be dealt with through individual choice in insurance and charitable giving, it strikes me that the light and noise surrounding the social security debate is simply more displacement behavior. Most people work very hard to avoid thinking about the realities of age-related degeneration and its consequences, sad to say. This is a big problem, since this sort of attitude helps to delay work on a cure for aging - large scale research requires a vocal, supportive, educated public.

Glenn Reynolds is another person echoing these sorts of thoughts:

Plague, of course, was once seen as inevitable, and there were even those who thought that efforts to fight it represented a challenge to God's will. We got over that, and I think we should recognize that aging is just another disease that science can't address -- yet.

But as the developed nations face a huge unfunded retirement liability, lots of people are talking about extending the retirement age to cut down on payments. I wonder if we might consider extending the retirement age through making people live longer, healthier lives -- perhaps by diverting a small portion of retirement money into aging research.

As is Randall Parker:

Given that the four major alternatives discussed above have major downsides why not consider science as a potential solution? After all, science will eventually produce solutions that cheaply cure or prevent all the major diseases. The only question is when. Acceleration of the rate of advance could not only reduce the size of future liabilities but could also have the very attractive added benefit allowing us all to get healthier and stay healthier for much longer.

...

My modest proposal for funding medical research: Change the major medical entitlements programs to require that 10% of all medical entitlements budgets go to fund medical research. Then when medical entitlements spending inevitably goes up medical research spending will go up proportionately. Yes, that will make the financial numbers for the medical entitlements programs look worse in the short run. But the money thereby spent will produce much larger savings for those programs in the longer run and will also produce treatments that will lead to great improvements in the health of the vast majority of people.

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The UN has issued its non-binding declaration calling for bans on therapeutic cloning, the last gasp for US-backed efforts to craft an international treaty criminalizing this important medical research. A few quotes from Wired, which wraps this into the broader topic of science and politics in the US:

The politicization of science policy in the United States has become a contentious issue in the past several years, with groups like the Union of Concerned Scientists criticizing the Bush administration for favoring political interests over scientific results. Now, that trend seems to be making international inroads.

Nations including Singapore, South Korea, Belgium and the United Kingdom blasted the declaration by the divided U.N. committee, calling it political posturing.

...

"In the scientific community in other countries we are ridiculed," said Kurt Gottfried, chairman of the Union of Concerned Scientists, in an interview. "It has certainly lowered our prestige across the world."

U.S. delegates to the United Nations supported a treaty to ban all cloning starting in 2002. After nearly two years of negotiations, the U.N. shelved attempts to agree on a treaty and instead delegates opposed to cloning pushed for a non-binding declaration as a compromise.

...

The United States is becoming notorious in the eyes of other countries, Gottfried said, as a nation that has allowed ideology to become a premise for science. That perception is sure to have harmful repercussions on the American science community, he said. Scientists are already leaving the country and graduate students are less uninterested in studying in the United States, he said.

South Korean politicians have declared they will not interfere with therapeutic cloning research:

South Korea will continue its stem cell research despite the anti-cloning resolution of a U.N. committee, according to the Ministry of Health and Welfare Monday.

"It is just a non-binding declaration and we have no plan to review our policy of allowing therapeutic cloning," the ministry's manager Kim Heon-joo said.

...

When contacted, Hwang's team echoed the stance of the health ministry, saying the U.N. resolution is simply a recommendation and that they would continue with their cloning research.

"We don't know much about the U.N. decision but we don't feel bound by it. We will continue our stem cell research as long as Korea sees it as legal," said SNU professor Kang Sung-keun, one of Hwang's top lieutenants.

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A fair amount has been happening in the US and elsewhere of late regarding stem cell research, funding and legislation. Fortunately, I don't feel so obligated to run off updates to these things now that a number of other folks are doing an excellent job in this area. Stem cell research has always been of great interest to me because it leads to regenerative medicine, which leads to cures for a wide range of age-related conditions ... which leads to incidental (rather than directed) healthy life extension. In addition, the research and capabilities required to make stem cell medicine a reality dovetail very nicely with the research and capabilities required to cure aging - it all comes down to understanding and controlling our cells in the end. So a focus on stem cell science (and legislation) isn't really as core to Fight Aging! as a focus on longevity science - I'm glad to see other people working on it. Some frequently updated blogs and news sources worth following:

• Hype & Hope
• Today's Stem Cell News
• CAMR News

A last note: now that things are heating up once more at the Federal level in the US, isn't it time you faxed your representatives to protest attempts to criminalize therapeutic cloning and embryonic stem cell research? The threat of anti-research legislation over the past few years has caused great harm to private funding - the cost of imposed delays in research into cures for age-related conditions is very high. You have a voice and can do something about this!

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Methuselah Foundation volunteer Kevin Perrott has put together a pair of video clips of coverage relating to Aubrey de Grey's presentation at the University of Alberta:

Aubrey de Grey coverage from CFRN TV: MPEG (27MB) | RealPlayer (6MB)

Kevin Perrott's interview with Global TV: MPEG (14MB) | RealPlayer (2MB)

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As always, good, thoughtful commentary from Randall Parker on some recent advances in stem cell research:

Pig Embryonic Cell Transplants May Work For Humans

My guess is that in the future both the use of starter cells to grow replacement organs in a human body and the transfer of fully grown xenotransplants will become commonly used treatments for organ failures. These treatments might even be used in a complementary fashion. Get an emergency full sized xenotransplant organ with immunosuppressive drugs to meet an immediate emergency need and then once the patient is stabilized and healthy transfer in some more immunologically compatible cells to grow yet another organ that will serve as the permanent replacement.

In the longer run it seems reasonable to expect the development of techniques that allow the growth of full sized immunologically compatible organs. Alternatively, full sized organs will be grown up and then immune system modification therapies will be developed that will be able to adjust an immune system to teach it that a transplant organ should be treated as native tissue.

I'm not so confident here; my suspicious is that the level of biomedical competence required to overcome the various hurdles associated with xenotransplantation will also allow organs to be grown from scratch from a patient's own tissue or remove obstacles associated with immune rejections between humans. From my admittedly distant position of viewing, it looks like scientists have about the same level of work remaining in any of these fields.

Young Mice Blood Turns On Regenerative Ability Of Old Mice Muscle

This is an important report. But I repeat my caution above: If the presence or absence of some compound(s) in the blood is reducing the repair ability of a variety of tissue types (and it seems likely other tissue types will also be found to be affected by young versus old blood) then there is a decent chance that this reduction in repair ability was selected for to achieve some benefit, most likely a reduction in cancer risk.

...

Suppose that changes in levels (either increases in suppressor molecules or decreases in cell growth stimulating molecules) of one or more compounds in the blood as we age happens in order to reduce the risk of cancer. Well, this is problematic for hopes to derive maximal benefits from replacing aged stem cell reservoirs with youthful stem cells. The old stem cells could be replaced with younger cells. There'd be immediate gains from lowered risk of cancer and relative improvements in the vigor and health of adult stem cells. So that is still worth doing. Yet the young replacement stem cells would still be restrained by levels of compounds in the aged blood. Here's the problem: If some but not all stem cell reservoirs have their stem cells replaced with younger stem cells it might not be safe to change the blood to make it more like young blood. It might be necessary to rejuvenate all stem cell reservoirs before the blood can safely be made more like young blood.

Here is an analogy: Imagine you have a car. It is old and it has 4 bad axles that will fall off if the car is driven too fast as well as a steering column that will fall apart at high speeds. Suppose you know how to replace the 4 axles but not the steering column. Well, if you replace only the 4 axles you still can't safely drive your car at high speeds. But with humans this problem is even tougher because there are many stem cell reservoirs located near every muscle and organ that would need to be rejuvenated before they could all have their level of stimulation by the blood safely raised to youthful levels.

Once really effective anti-cancer treatments (even treatments that kill all precancerous cells) are developed then most (all?) safety worries from making blood young again would go away. Any cancers that popped up in response to having youthful and growth-stimulating blood could quickly be slain or they could be slain even before the blood was rejuvenated. So great cancer-slaying treatments would make rejuvenation treatments easier to implement.

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It is always good to see a high-value application emerge from a field of science that will eventually lead to healthy life extension, even if that application itself doesn't have any effect on our life spans. Applications are bridges to pools of money and consumers - the process of serving those consumers helps to fund and broaden the underlying science. Cloning animals (especially pets) is a good recent example, as is stem cell based hair restoration. Wired offers another potential application of stem cell science that could tap into a large pool of money: breast implants.

What could be better than breast implants? Why, breast implants that continually repair themselves, of course. Saline implants can leak, rupture, interfere with mammograms, and lose their shape. But scientists are studying ways to make breast augmentations from stem cells, which are famous for their self-renewing capabilities. Researchers at the University of Illinois at Chicago will publish a study in the April issue of Tissue Engineering showing that stem-cell tissue implants in mice kept their shape longer than traditional implants.

Younger fields of research need as many of these lucrative bridges to money and consumers as possible in order to grow the pool of funding, scientists and knowledge. Private funding is quite capable of outweighing public funding, but it won't come out to play in the absence of a clear, defined market.

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Aubrey de Grey's presentation at the University of Alberta went well by all accounts. April notes:

When people begin to ask questions about the consequences of curing aging as we know it, it signals to me that they can't refute de Grey's arguments about the *possibility* of curing aging, so they turn to arguing about the *desirability.* It is indeed hard to refute the basic premise that if we could repair the damage caused by being alive, there's no reason to believe that we can't continue being alive indefinitely (or until we get squashed by a truck on the New Jersey Turnpike.)

The problem with arguing about the *desiribility* of curing aging is that it requires one to argue that people have the moral obligation to die. We would never say to a representative of the American Heart Association that curing heart disease is bad because it would cause lots of people to live longer. We would never tell a nurse who works in the neonatal ICU that it would be better for those palm of the hand-sized babies to die instead of growing into healthy, productive adults. So why should we argue that just because someone is 80, or 90, or 100, or 110, or 150, they should make the planet less crowded by going off somewhere to die?

For me, watching from afar, the most interesting part of this event was the comparatively large amount of globally accessible press attention it generated - which in turn is reflected in the blogosphere - all due to the hard work of volunteers and this useful internet thing you might have heard of. It shows that even comparatively minor events can be used to very good effect in continuing attempts to educate the public ... when the media are appropriately prepared and cultivated, that is.

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As a counterpoint to a flurry of articles on healthy life extension and biological immortality (or vulnerable agelessness) in the past week, here is an editorial that neatly distills a number of different (and debunked) pro-death ideas into a few short paragraphs.

Humanity has always found its greatest triumphs, if not its very reason for being, in struggle. Those regarded as our greatest leaders - people like Churchill, Lincoln, and in Canadian terms, Trudeau - are defined more by what opposed them than what they did. Much of invention is born from a struggle of some kind or another, whether it's against nature or just trying to get information out quicker. Even in our everyday lives, competition inspires us to something more; we'll often try harder or do better when we have someone or something we’re trying to best.

And with the removal of the threat of death, we'll have done away with arguably the biggest competition we have. One doesn’t need to point out the countless works of art, to say nothing of entire philosophies, that have tried to come to grips with man’s mortality. Ignoring the obvious religious significance of such an event, if man no longer fears death, what reason does man have to continue living? We’ll have, for lack of a better term, won.

This isn’t to say that the arrival of an elixir of life will be met with mass suicides and depression across the world. No, people will probably continue on pretty much as is, but that would be precisely the problem. Things would stagnate; people would find no reason to do much of anything. Why work, why create, why learn, why suffer, why strive, why believe, why love, why hate, when in the end, it's likely those who take the safest path will end up ahead, in the form of living longer? The world will be locked in permanent suburbia, where too much or too little will lose out in favour of just enough.

Obviously, this happens enough in our world as is; people will almost always settle for mediocre over something that might just be good, but might also be bad. But now, at least, there is one thing that can push us into something more: the fact that, eventually, we're not going to be around anymore. If nothing else stirs us, at least the cold, hard truth of mortality will give rise to something more than sitting on the couch.

But to remove that, to remove the one thing that humanity has always struggled against, is to take out something that is essentially human. If this ever happens, we might just live forever, but I doubt we'll have any reason to.

How silly! How shortsighted! An infinity of far, far greater challenges awaits us after this comparatively simple fix for less desirable characteristics of our biology - exploring the solar system, traveling to the stars, cataloguing all life on Earth, terraforming mars, understanding the roots of intelligence, building a science to determine whether or not we have free will ... I could go on. Personally, I'd like to be around and in good health to try my hand at helping to overcome a few of these future challenges.

More to the point, you, oh writer of editorials, may feel this way, but a great many people fail to share your pessimism, lack of foresight, world-weariness and death wish.

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Back at the end of 2003, I proposed that we need a "suitable outrageous extreme" in our promotion of healthy life extension.

The middle of the road, "reasonable" position in public or political debate tends to gravitate to midway between what are perceived to be the two opposite outrageous extremes, regardless of the actual merits of any of these positions.

With this in mind, it is occurring to me that part of the ongoing problem in the modern political debate over healthy life extension is that our "outrageous extreme" has always been a tentative, reasonably proposal that medical research carry on and that near-term technology would seem to allow us all to live a little longer ... say, to 150.

I mentioned Aubrey de Grey's figure of 5000 years for the life span of an ageless human (based on accident rates - you can find more information on that sort of calculation in "The Tithonus Option is Not an Option" at the Longevity Meme) as a suitable outrageous extreme at the time. I was pleased to see a recent example of this sort of psychology at work in an amusing column at the National Review:

Here we are talking about the federal retirement system facing possible disaster because a lot of people are living into their 80s and 90s. Meanwhile, out in the real world of science, medicine, and hypercompetitive Americans, 90 years old is already peanuts.

...

Normally skeptical journalists are reduced to goo by any news from the longevity frontier. Who cares if a lot of the science is dubious and contradictory? There's a massive audience for this stuff, and the media are only too happy to provide it, quality be damned. Now, with Baby Boomers on the verge of oldster-hood, there's a lot more to come.

Cautious longevity scientists say that it may soon become common for people to live up to 100 or 120 years. Bolder optimists extend it to 150. And there's the prominent inventor and futurist Ray Kurzweil, who takes 250 vitamins a day and co-authored the recent book Fantastic Voyage: Live Long Enough to Live Forever. The book, which got serious coverage in elite media outlets, contends that if we can just all live another 20 or 30 years, we'll be in the age of "intelligent nanobots," tiny machines that will go into our bodies and eradicate all disease and damage, allowing us, potentially, to live forever.

Between these extremes is a Cambridge University scientist named Aubrey de Grey, who has said that people born in the next century (i.e., beginning 95 years from now) may have a life span of 5,000 years.

So 5000 years is now "between these extremes" and must thus be a sensible prediction, never mind the underlying science. While despairing of any attempt to inject rational, factual discourse into mainstream journalism, I think that we are making progress in the marketplace of ideas. That progress will translate to an easier time for scientists working on longevity medicine - when people are producing good science to back up projected future life spans in the thousands of years, proposals for funding to extend the healthy human life span by a few decades look quite reasonable.

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Some very characteristic comments from aging researcher Leonid Gavrilov over at Longevity Science:

Where are the generous sponsors and philanthropists willing to support human longevity studies?

Aauuu!

The generous sponsors are, of course, somewhat lacking at this moment in time. This is a problem noted by Gavrilov at greater length in an article at the Longevity Meme. Why longevity research funding is hard to come by is explained in an excellent piece by biogerontologist Aubrey de Grey - there is a problematic feedback loop between scientific conservatism, funding sources and public opinion. The normal process of organization, paradigm shift and debate within the scientific community is proceeding at a slow pace, but scientists also face obstacles arising from a lack of public awareness, widespread misconceptions and poor education. Research advocates and their projects (like the M Prize) can help to make the jobs of scientists like Leonid Gavrilov and Aubrey de Grey a great deal easier by raising awareness and increasing understanding of healthy life extension research - thus making funding much more likely.

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The busy bees of the Methuselah Foundation are doing a great job in generating press for Aubrey de Grey's presentation on the 15th. It just goes to show what can be done when you put your mind to it - excellent practice for engaging the larger players in the media. Another good interview has shown up in the University of Alberta's ExpressNews paper:

De Grey does admit his timeframe may be "somewhat overoptimistic." But he argues that only by treating it as a realistic goal do we stand any chance of making it happen. The main obstacle to progress, he said, is that many biologists work on the problems of aging in isolated experimental silos, too rarely pulling back from their work to take the long view.

"You don't have departments of theoretical biology, but you ought to," said de Grey. "When I actually identify a way in which different strands of biology could be put together for a productive purpose, I find it quite easy to get people interested in listening to each other once they’ve heard about the possibility."

The question de Grey faces perhaps more than any other, however, has less to do with cell biology than ethics or social science – is it desirable to extend human life, given that our world is already overpopulated? For de Grey, it's not up to him, or even any of us, to make that call. It is, however, a fundamental right of future societies to decide whether to adopt anti-aging therapies once discovered and whether the accompanying sacrifices are worth it.

"There are good reasons to suppose that we may genuinely have to make hard choices as a society," he said. "I like to be quite stark about this ... There's a good chance that we will end up having to make a choice between having fewer children than we really want or living less time than we really want.

"This is a choice that society of the future is entitled to make for itself as opposed to us trying to second guess ... by not developing these things and thereby forcing on society the requirement to choose death rather than childlessness."

A number of important talking points are buried in that short except. Firstly on timescales: if everyone accepts that developing working anti-aging medicine is going to take a long time - absent the work done to confirm this proposition - then this research will certainly take a long time. This is because funding will lag; no funding group devotes much time and money to what are considered to be extremely long term projects. Thus pessimism, reasonable or unreasonable, becomes a self-fulfilling prophecy in scientific and medical progress. Aubrey de Grey has good science and good motivations behind his timescale claims; in order to have any chance of reaching the goal of greatly extended healthy life spans in our lifetime, we need to support this research.

On overpopulation, I'm of the view that it's a nonissue based on what we know of human behavior and economics; Max More treats this subject well in his essay on Superlongevity and Overpopulation. Nor is the world currently overpopulated. Too many people mistake the terrible problems caused by politically-maintained poverty for overpopulation, but this is not a case of too many people - rather, it is an absence of the rule of law and undercapitalization of existing, unused resources. Here, as in many other aspects of healthy life extension and related topics, we need a better, more effective approach to education and the presentation of our ideas.

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An e-mail from the Gerontology Research Group references an interesting projection from Leroy Hood of the Institute for Systems Biology:

One of our GRG Co-Founders, Dr. Robert Nathan, asked Dr. Hood during the Q&A Session that followed his lecture this afternoon at CalTech (attended by Prof. David Baltimore, CalTech President), "But what about aging, which you hardly mentioned in your talk? Shouldn't that receive some special focus of attention in the new Systems Biology?"

Hood replied: "We've made some spectacular progress in aging research using model organisms like C. elegans and Drosphila. Next, we have to apply this knowledge to humans. I predict that, by applying the principles of Systems Biology, in ten years we can expect to see a 10- to 20-year increase in average life expectancy for the general population. In ten years, with the cost of DNA sequencing coming down by another 100,000-fold due to advances in technology, every single person in this room, who wishes, will have their unique DNA sequence routinely placed in a computer data base that will lead to custom therapeutic interventions that are tailored to their individual, idiosyncratic genes."

The point regarding cost reductions is one that is frequently made by Randall Parker. I see advances in life span of the sort projected by Leroy Hood as incidental life extension - not arising due to deliberate efforts to extend the healthy human life span, but rather due to increased capabilities in medical interventions across the board. According to the reliability theory of aging, the more cellular wear and damage you prevent throughout your lifetime, the longer you will live. Incidental life extension isn't a bad thing, but directed, serious anti-aging research is needed in order to reach escape velocity - in which healthy life span increases faster than we age - in our lifetimes.

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Jay Fox comments on debates over SENS (Strategies for Engineered Negligible Senescence) within the healthy life extension community.

The important thing to keep in mind is that, in debating how "good" an anti-aging treatment is, we only need to consider whether it will allow people to live long enough for something better to come along. In other words, the first effective anti-aging treatments don't need to completely cure aging, they just need to buy us time for something better.

In that light, Dr. de Grey has admitted that his 7-point strategy is likely not going to be a true cure for aging. It's not good enough to cure aging, but he believes it will be good enough to buy us time, so much time that future advances will continue to buy us more time, etc. In effect, once his 7-point plan is achieved, future biomedicine will always stay at least one step ahead of the aging process. This is what Dr. de Grey means when he says "escape velocity".

I do not doubt that Dr. de Grey's plan will work, and so it may be perceived as somewhat hypocritical that I am sometimes critical of Dr. de Grey's plan. What needs to be made clear is that I don't doubt that Dr. de Grey's plan will work; what I have reservations about is whether it will be available soon enough, and broadly enough, to save the most lives possible. That is, I believe that there are other strategies which will make escape velocity occur sooner, for more people, and in effect, save more lives.

My position on these sorts of discussions is that we are still in the stage of needing many more qualified and useful people (e.g. scientists, folks with money to spend on research, advocates with a large audience, etc) to take part. It's never too early to critique and improve ideas - especially when it comes to getting to the end goal more rapidly - but we still need to devote much more effort to raise awareness and bring new faces to the debating table.

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A brief interview with biogerontologist Aubrey de Grey can be found in the February issue of Wired magazine:

WIRED: Your Gerontology piece claims that the current approach to prolonging life - developing drugs that mimic nutrient deprivation - is wrong. How so?

DE GREY: I present a detailed evolutionary argument that caloric restriction in humans will give only a very small increase in lifespan. Starved worms and flies can live many times longer than normal, whereas mice can live only about 40 percent longer and dogs only 10 to 15 percent. We'll get only two to three years from that approach. Better than nothing, but not enough. This is a big deal because the majority of academic-led biotech startups aimed at postponing aging are developing drugs based on caloric restriction.

WIRED: You think we can actually reverse aging instead of just slow it down?

DE GREY: That's right. The rejuvenation therapies we are on the verge of developing will actually repair cellular damage. The reason I think we're close is that we can describe what aging is in such minute detail, and we can also describe feasible, foreseeable ways of repairing each of those categories of damage that go together to make up aging.

You can read Aubrey de Grey's work in detail at the Strategies for Engineered Negligible Senescence website, and you can help to make his view of the future of rejuvenation research a reality by contributing to the Methuselah Mouse Prize fund.

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As noted recently by a number of commentators, the State of the Union address suggests that efforts to criminalize therapeutic cloning and embryonic stem cell research in the US will continue.

Sen. Sam Brownback (R-Kansas) and Rep. Dave Weldon (R-Florida) have been trying to push their anti-human-cloning bills through Congress since 2001, with Bush's unofficial stamp of approval. If either bill becomes law, researchers who violate the law would face up to $1 million in fines and jail time. Such a law could also put a kink in California's stem-cell initiative, which dedicates $3 billion to stem-cell research over the next decade, and could cause problems for similar efforts in New Jersey, Maryland, Wisconsin and several other states.

"I think what we have here is a real civil war over stem cells, and if the president has his way with this policy and we see the Brownback bill passes, it's going to undercut every single state funding initiative for stem-cell research,"

...

"I would expect to see the Weldon and Brownback bills reintroduced soon. ... What's interesting about the president's statement is that he goes further than Brownback in seeking a ban on all embryo creation for research, whether through (somatic cell nuclear transfer) or in vitro techniques, and states his intention to work with Congress to get this into law."

Federal criminalization of this science will wreck important research into cures for age-related conditions - diabetes, Parkinson's, Alzheimer's, cancer, and many more - and block a greater understanding of biochemical processes. It will drive away the billions in private funding still waiting in the wings. So much damage has been done and time wasted already - hundreds of thousands of people continue to suffer and die each and every day.

It is a good idea to make our opinions known before this goes much further. A sample letter to your elected representatives can be found at the Longevity Meme; I strongly urge to take it as a basis for your own letter. You can find fax information for your representatives at Congress.org - a fax is much more likely to be read than any other form of communication with politicians in the US.

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This should be of interest for those who like to keep tabs on what the anti-aging marketplace is up to: if you cast your eyes over the A4M website, you'll note a strong focus on the growing field of regenerative medicine these days. A4M are influential in the sense that they both reflect and help determine marketing and presentation within the anti-aging industry - reputable and disreputable groups included. Regular readers will recall that I have my issues with the way in which A4M conducts business, especially as it relates to their conferences, but a strong focus on regenerative medicine from this crowd can't be a bad thing. I don't think they have the clout to hurt the public view of regenerative medicine in any way at this time, and a greater influx of real, working science may chase out some of the bad actors in the industry. This has been coming for a while; the last update to the A4M definition of "anti-aging medicine" incorporated language that would not sound out of place in a prospectus for future regenerative medicine.

To this challenge, anti-aging medicine arrives as the new health care paradigm, offering a solution to alleviate some of the burden of this burgeoning older population. Anti-aging medicine, an extension of preventive health care, is the next great model of health care for the new millennium. This model is based on the early detection, prevention, and reversal of aging- related diseases.

One sea change I hope to see in this marketplace is good medicine chasing out bad medicine - if real, demonstrable therapies for age-related conditions exist, then the modern pill and potion salesmen have less of a leg to stand on. Good riddance to them, since their actions greatly damage the credibility of serious research into slowing or reversing the aging process itself.

As a last note, please do read my commentary on anti-aging medicine and science at the Longevity Meme before taking anything you read at A4M or related sites at face value.

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James Hughes interviewed April Smith, the new full time fundraiser for the Methuselah Foundation for his show, Changesurfer Radio. You should download the audio and give it a spin. Speaking of fundraising, April is already hard at work - so if you have good connections or a good idea to help raise the profile and funding level for the Methuselah Mouse Prize for anti-aging research, now would be a great time to speak up.

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Here is an interesting scan of an old article on whale life span that I hadn't noticed until now (it was mentioned in an article at Lew Rockwell that touched on healthy life extension - a rather surprising sign of the way in which our ideas are spreading).

In studies that could rewrite biology textbooks and establish whales as the longest-lived mammals on Earth, scientists in Alaska and at the Scripps Institution of Oceanography in La Jolla have estimated the ages of three bowhead whales killed by Inupiat Eskimos in northern Alaska at 135 to 172 years. At the time is was killed, a fourth bowhead whale was believed to be a stunning 211 years old, the researchers concluded.

Age was estimated by looking at chemical traces in the eyes and ivory harpoon tips from a century or more ago embedded in the whales. Fascinating stuff. I've mentioned the Ageless Animals website before at the Longevity Meme; the scientific findings reported there form a good rebuttal to some objections to healthy life extension. Many of these very long-lived animals are not so different, biochemically speaking, from us humans. If animals can live such very long lives, then it's certainly within the realm of possibility to develop therapies to greatly extend human healthy life spans.

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Preston Estep of Longenity, Inc. chose to use the Technology Review forums for the recent Aubrey de Grey cover article to comment at length on the science, inaccuracies in the article and his own views on timescales and the difficulty of developing serious anti-aging medicine. Aubrey de Grey then responded, and think the two pieces are worth a much wider audience. Unfortunately, individual posts in the TR forums can't be linked directly, so I'll reproduce the exchange here in full:

Dear Editors,

I earned my Ph.D. in George Church's lab at Harvard Medical School, a antastic breeding ground for next-generation technology research and development, and for the last few years I have been President and CEO of Longenity Inc., a Boston-area biotech company doing aging research. So it should come as no surprise that I have been an avid reader of Technology Review (TR) for many years, and that I read with particular interest your cover story on Aubrey de Grey.

Even though I have a long history as a reader I have never, until now, felt compelled to write a letter to TR.

First, I do not agree with de Grey's SENS plan; however, I do agree with certain aspects of the "life extension escape velocity" theory of human longevity (as it is referred to in the original article) -- but not with his overly-optimistic version of it, especially his estimated timeline for its occurrence. I count myself in the mainstream of scientific aging research and I think the problem of life extension is far more vexing than does Dr. de Grey.

Dr. de Grey's belief that he knows the cause of aging and completely understands the path to its control, and even reversal, is accurately summarized in the article which states "He bases his certainty that there are only seven such factors on the fact that no new factor has been discovered in some twenty years, despite the flourishing state of research in the field known as biogerontology...".

Indeed, Dr. de Grey does believe this, and he is wrong. Moreover, unlike Sherwin Nuland or other casual critics of the SENS plan -- and unacknowledged by Dr. de Grey -- mainstream scientists have produced substantial evidence not addressed by de Grey and his plan. More importantly, certain of these data are related in a way that gives the immortalist or transhumanist particular discomfort since they suggest that the SENS plan does not address the primary -- and maybe the most difficult to control -- general aspect of aging: entropy.

In plain English, the loss of order and information essential for biological function.

The general concept of biological entropy encompasses several dynamic phenomena including cellular dedifferentiation or transdifferentiation (in which normally homogeneous groups of cells of a particular type become more heterogeneous), nuclear and mitochondrial mutation, chromosomal instability, aberrant methylation and other directed modification of the genome, loss of chromatin meta-structure, or changes in other aspects of transcriptional or signaling networks that render them more noisy and less robust over time. Many recent experiments, especially large-scale microarray transcript profiles of aging, support this general concept of time-dependent decay of orderliness (for examples, see references 1, 2, and 3).

It is difficult to imagine how the information-rich order that is established during embryogenesis and development can be restored or replicated. A critical evaluation of the SENS plan shows that, except for nuclear and mitochondrial mutation and instability, this general concept is almost entirely overlooked, and in vivo order and information content are assumed to remain at a high level.

This almost certainly mistaken assumption is betrayed by the logic of the entire SENS plan, and in particular by points 1 and 3, which direct the introduction of stem cells into a new environment of a person's body where they are to -- almost magically! -- assume specific roles. Guided by what signals are they to assume these roles? By the highly orderly signaling that already exists in vivo, naturally. And herein lies the problem. We know that differentiation of stem cells into other cell types is a highly regulated process that involves factors both extrinsic and intrinsic to the cell. Extrinsic factors include direct cell-cell interactions with tissue-type specific cells, and signaling with distant cells through various small molecules, including growth factors, hormones, and neurotransmitters.

And what will be the result if -- as current evidence suggests -- that many of these cell-extrinsic signals are gradually lost, or become dysregulated, over time? Then the newly introduced stem cells probably will simply contribute additional noise to these signaling networks. So, far from fixing existing problems, this proposed solution simply exacerbates them.

Even if these extrinsic factors remain essentially unchanged during aging -- which is highly doubtful -- stem cell biology is in its infancy, as is engineering of the genome in human cells; therefore, we cannot assume that all stem cells are equal, and that their paths of differentiation are controllable or predictable. Many of the factors that likely guide and regulate cellular differentiation, genomic stability, and cellular information content likely have not yet been identified.

And we are expected to have full control of these extremely complex processes within the next twenty years? I won't say it is impossible, but I will say that we are nowhere near the engineering phase since we do not clearly understand the nature of the problem. To further complicate matters, in the past few days it has been announced that all existing embryonic stem cell lines have been contaminated by mouse feeder cells.

What unforeseen hurdle will come next?

As baffling and challenging as are de Grey's positions on aging and how to deal with it, Dr. Nuland's seem simple and pretty straightforward: if it is conventional, it is good. Dr. Nuland claims he doesn't want to live excessively long, just a really long time for a human. So, this is how he feels...for now; however, once others live beyond the current upper limit, then he'll want to do it too -- but not until then. But, then it will be fine -- desirable, even -- because others will have done it. There are several problems with this attitude; primary among them is that it gets us nowhere. What of importance would ever be accomplished if this attitude prevailed, if everyone were a follower? This is a perspective completely lacking vision and imagination.

The choice not to extend healthy and productive lifespan also implicitly grants to the young an unearned degree of respect not accorded to older and wiser people. We are trained by innate mechanisms, refined by millions of years of evolution, to think highly of the young, to aspire to their advancement and betterment, and even to sacrifice the advancement and betterment of ourselves in this cause.

But I agree with the general proposition that this behavior is subject to modification, primarily because with wisdom comes the realization that while young people have certain admirable virtues, they also are far more violent, irrational, ignorant, and mistakenly -- and sometimes even dangerously -- idealistic. A great quote by H.H. Williams highlights a significant difference between young and old, and it succinctly summarizes why I have such admiration and respect for older people:

"Furious activity is no substitute for understanding." I think that a world in which healthy and wise older folks greatly outnumbered wild and reckless younger ones would be a fine place to be.

And then there is Dr. Nuland's speculation about the killer benevolence that will bring about the end of the world. While I don't think his apocalyptic vision completely unreasonable he should be cautious about casting stones; de Grey, at least, has methodically compiled some evidence to support his theories, although, it is far from sufficient to tackle the enormity of the problem. Nevertheless, at least he is trying -- very hard, in fact -- to do something I consider to be noble and worthwhile: he is trying to advance the cause of humanity -- all of humanity -- whether or not certain individuals want any part of it.

But he cannot succeed if he continues to pretend that his fellow scientists disagree with his theories out of ignorance. Nobody, not even de Grey, is above the normal scientific exchange in which unpleasant or unanticipated facts must be accounted for by either disproof, or by modification of existing theory, not by ad hominem dismissals of the messengers as being too "ignorant" to understand his brave and advanced conjectures. Methinks he doth protesteth, and pretendeth, too much.

Preston Estep III, Ph.D.
President and CEO
Longenity, Inc.

REFERENCES

1. Ly DH, Lockhart DJ, Lerner RA, Schultz PG. Mitotic misregulation and human aging. Science. 2000 Mar 31;287(5462):2486-92.

2. Whitney AR, Diehn M, Popper SJ, Alizadeh AA, Boldrick JC, Relman DA, Brown PO. Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1896-901. Epub 2003 Feb 10.

3. Welle S, Brooks AI, Delehanty JM, Needler N, Thornton CA. Gene expression profile of aging in human muscle. Physiol Genomics. 2003 Jul 07;14(2):149-59.

Aubrey de Grey replied as follows:

I thank Dr. Estep for his critique of my ideas and of their portrayal by Sherwin Nuland. I particularly thank him because it is so rarely that anyone with extensive knowledge of the biology of aging actually puts into words why they think my projected timescales are unrealistic (and indeed, it's the first time Estep has done so).

Firstly I must correct one statement: Estep claims that I believe that I know the cause of aging and completely understand the path to its control. That is not correct: I only claim that we know enough about the causes of aging and ways to control it that we have a 50% chance of achieving life extension escape velocity within 25 years assuming reasonable funding for the next ten years, and that having reached that point we will stay "ahead of the game" thereafter by refining those therapies faster than their incompleteness catches up with us. Again, in the second segment of his popst he discusses "full control in 20 years" -- which I do not claim we will have. He continues by losing the essence of my claims completely when he mentions the feeder cell problem: this is a problem of politics and politics alone. It has no relevance to the rate of progress in postponing mouse aging, which I claim (and have often said and written) will be the key to overturning all political objections to human rejuvenation therapies overnight.

Estep's error in his argument about entropy is to overlook the fact that cells introduced into the body in a cell therapy (of any kind) will in general have less entropy than the ones they replace did. He is quite right that they consume information while they are settling in, but thereafter they provide it. This can maintain a high degree of order indefinitely, even in the face of increasing entropy of all cells while in situ. I don't remotely deny that cell therapy is very tricky and complex -- indeed, getting the cells into the right phenotypic state before the therapy may generally be even harder than causing the right differentiation (or lack of it) in situ -- but it's not akin to building a perpetual motion machine, which is how Estep seems to characterise it. He alludes to the existence of "substantial evidence not addressed" by me and SENS, but the only references he gives are to the changes of gene expression with age, which of course occur but do not tell us anything about what can be done to reverse them.

I repeat, however, that even though this is a rather simple error (in my view) I am grateful to Estep for at least having a go at finding decisive holes in SENS. We need more of this.

Estep ends by suggesting that I am indulging in ad hominem dismissals of gerontologists who disagree with my proposals. Not so: I derive my view (that virtually no biogerontologists know enough about the state of current progress in several of the SENS areas to comment usefully on how long they will take to be completed) purely from talking to them and discovering how much they don't know. Most biogerontologists do not dispute this, which is the main reason they don't engage me in the sort of detailed, nuts-and-bolts discussion of feasibility that we need. I engage extensively in such discussion with the scientists who are actually working in these areas (sometimes even convening meetings for the purpose, documented at SENS3 and SENS4), and am constantly learning from those scientists about new difficulties and also new breakthroughs -- but those scientists are, by and large, not biogerontologists, and are working on these problems/technologies for reasons other than the postponement of aging.

In a recent Immortality Institute thread on a different - but tenuously related - topic, we can find some further interesting comments from knowledgable posters on Estep and de Grey's points. Just scroll down to read it all.

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Alex Beam of the Boston Globe authored a rather characteristic filler piece on the Technology Review cover article profiling biogerontologist Aubrey de Grey - sniping at all sides without examining anything so prosaic as, say, the actual science involved. I am singled out as an invading crackpot at one point; I feel I've crossed a threshold of some sort. At least he bothered to e-mail me to verify my name and gender before starting in with the slander.

Still, no such thing as bad publicity. Let the know-nothings snipe and make snide remarks. If we've seen anything, it's that people open to examining the merits of healthy life extension research will hear the message loud and clear through many layers of pro-death (and other forms of) humbug.

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Some recent work on cell senescence demonstrates one of my recurring points: we have reached the stage at which all new knowledge of cellular biochemistry and genetics found in the course of a single field of research has wider applications. We are seeing the ties between aging and cancer, for example, and the ways in which different conditions related to the same biochemical processes.

Earlier studies have demonstrated that as cells reach senescence, an alteration in chromatic structure called senescence-associated heterochromatin foci (SAHF) silences the genes that trigger the cells growth. This discovery reveals the process of SAHF formation. SAHF are domains of tightly packed chromatin that repress activity of the genes that normally trigger cell proliferation. The Fox researchers have identified at least three proteins in the cell that contribute to the formation of SAHF. These proteins are called ASF1a, HIRA, and promyelocytic leukemia (PML). Scientists have known for a while that PML suppresses the formation of this type of leukemia, but do not know why.

This research suggests the possibility that PML arises because the PML protein is not able to do its job in forming SAHF. If this is true, this study might help in the design of therapeutic drugs to treat cancer patients and even lessen some aspects of aging. Additional study in this field will define the molecular details by which HIRA, PML, and ASF1 and formation of SAHF may also be a factor in other human cancers.

The incidental benefits of fields like stem cell research and modern cancer research - focusing as they do on cellular biochemistry - are large. This new knowledge will serve as a basis for the targeted healthy life extension research of the future.

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Randall Parker makes some helpful observations on scientific progress towards controlling stem cells:

I think it is inevitable that methods will be found to dedifferentiate (i.e. make less specialized or less committed to a single purpose) both adult stem cell types and fully specialized cell types (e.g. liver cells or skin fibroblast cells) to turn these cells back into less differentiated stem cells and even all the way back into embryonic stem cells. So for the production of motor neurons we will not always be limited to starting with embryonic stem cells to pass them through that 2 week window in early embryonic development during which embryonic stem cells can be converted into motor neurons. In fact, compounds that cause cellular dedifferentiation have already been found. I expect many more techniques for dediffentiating cells will be found.

Think of cells as enormously complex state machines. Currently it is much easier (though not easy in an absolute sense) to coax cells to switch from the embryonic state into other states. The reason for this is pretty obvious: Cells in the embryonic state must be capable of transitioning through a series of steps into all the other states (e.g. to the state that heart muscle cells are in or the state that liver cells are in or the state that insulin-secreting Pancreatic Isles of Langerham cells are in) because embryos develop to produce cells in all those states. They must have that capacity or else a full organism couldn't develop starting from an embryo. However, just because there are some cell state transitions that do not happen under normal conditions of development that doesn't mean that those transitions can't be made to happen with the right (and waiting to be discovered) sequences of hormones, growth factors, gene therapies, and other stimuli.

Just because some day we will have methods to turn non-embryonic cell types into all other cell types that does not mean that avoidance of the use of hESCs in developing therapies has no future cost in terms of the health of some fraction of the human population. There is a very real possibility that hESCs can be developed for some therapeutic uses faster than other cell types can be developed for all uses. My guess is that at least for some purposes hESCs will be ready to provide treatments faster than adult stem cell types can be coaxed to do the same. We will see more research results such as this paper offering the possibilty of a cell therapy treatment for which the development of alternative non-hESC based cell therapy treatments are a more distant prospect.

I view research into stem cell based regenerative medicine as a real boon - in addition to all the obvious end goals, it is forcing scientists to uncover, understand and eventually manipulate the fundamental workings of our cells. Much like cancer research and AIDS research required the development of new basic science that has proven its worth across the board, stem cell research is spurring development of a scientific groundwork for the advanced medicine of decades to come.

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