Via Responsible Nanotechnology, here is an interesting illustration of the pace of progress:

The first image is from the game Pacman, released in 1980. At the time it was considered to be an innovative video game.

The second image is Half-Life 2, released just a few months ago. It too is considered to be an innovative video game.

These two games are separated by only 25 years, yet they look like they are from completely different planets. One is a flat, pixelated, handful-of-colors-on-a-mostly-black-screen game. The other is a photo-realistic real-time romp through an artifical world of incredible depth and detail. The two games cannot be compared. It would be like comparing a backhoe to a spoon.

An awareness of this rate of change - which could just as well be illustrated by examples pulled from the world of medicine - is why advocates for healthy life extension are pushing for funding now. Transformative technological change in two decades, while perfectly possible, can only be achieved in an environment of public support, expressed desire and high levels of funding. Substantial progress towards working anti-aging medicine is quite possible in a time frame of 25 years - just as substantial progress in cancer therapies has been made in the past 30 years - but only if we start from a position of widespread enthusiasm and a large funding base.

Unfortunately, we don't have either of these items yet, but we're working on it - join in and make a difference!

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For those of you interested in perusing the recently released National Academies Guidelines for Human Embryonic Stem Cell Research, here is a link to the text online. (The summary itself is twelve pages, so that should keep you busy for a while). I gather that various folks were working behind the scenes with the intent of ensuring that the end result would be a document that could be adopted by the California Institute for Regenerative Medicine (CIRM) - no sense in duplicating work when reuse can speed things up. Unfortunately, it looks like the rules prohibit the very necessary and ethical practice of compensating human egg donors - and various bioethicists would like to see even more prohibition of compensation. This is, not to put too fine a point on it, nuts: another fine example of what the medical establishment thinks of free choice, individual rights, personal responsibility and a free market.

If the folks managing CIRM want to see more rapid progress - as rapid as a government-managed program can be, that is - then they will refrain from adopting that part of these guidelines.

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In the not so distant future, biotechnology will come to look much like present day software development. This is somewhat inevitable, given the falling cost of computing power. While a great deal of the newest biotechnology is powered by advances in computational technology, ultimately everything bio will benefit. Most currently real world experimental techniques - rather than just a select few - will become cheaper to carry out in simulation. Why spend millions keeping racks of mice when you can spend hundreds of thousands on reliable, tested software to do the same job - software that will become cheaper by an order of magnitude with each passing decade. Before this transition is even mostly underway, we will see an unleashing of talent comparable to that in open source software development today. Just look at how far and fast software has come in the last ten years compared to the ten before that...

For my money, the most interesting part of this process is the enabling effects of cheap computing power - and the tools to take advantage of it - on people who are not professional researchers. To put it another way, the line between researcher and nonresearcher will become very blurred, just as the line between programmer and nonprogrammer is today. The present open source software development community contains diverse individuals, small teams, academic, non-academic, corporate and non-corporate groups producing solutions for specific problems that bother them or inspire them. In the future, equally diverse organizations will form and collaborate to produce solutions for health and longevity using open biotechnology yet to come.

The most important result of open information sharing and falling costs is the way in which it opens up the priesthood - be it of programmers or biotech researchers - and allows a much wider range of people to add their skills, time, desires and ideas to the mix. Just as open source software development has led to a melting pot of innovative designs, better software and a blurring of traditional lines, so too will the open biotech movement of the future.

Looking at the tremendous dynamism and energy of the current software development space, I think that this can only be a good thing.

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You'll recall the recent study on mortality and weight that I wasn't overly impressed with. I've seen one or two articles of late in which negative comments were made about calorie restriction in this context. In an e-mail to the Extropy Chat list, Brian Delaney of the Calorie Restriction Society notes the fallacies inherent in this sort of thing:

No conclusions about the benefits of a CR program can be drawn from studies showing a correlation between weight and mortality. People trying to draw such a conclusion are committing a serious logical error, one with potentially devastating health consequences for those who buy the error.

"CR leads to a reduction in weight." Yes.

"A reduction in weight is a sign of CR." No.

CR is not about being thin. Naturally obese mice (ob/ob) on severe CR are still chubby, but live much longer than naturally thin mice not on CR. Energy-restriction shifts resources away from growth and reproduction towards repair and maintenance. Doesn't matter what you weigh.

Indeed, the assumption (or false conclusion) that "accidental/unintentional CR" is more likely to be found among the underweight is not only wrong, it may even be backwards. People in the countries whre these mortality studies tend to be conducted who are naturally thin have LESS reason to restrict their food intake (and note: food restriction is not the same as Calorie restriction -- though that's a minor point), given societal pressures to be thin.

The way to determine whether or not CR reduces mortality is to look at people on CR and compare them to people not on CR. This is being done. Some initial results include those reported by Fontana [1].

It will take a long time before we can be certain that CR dramatically reduces mortality, but it seems extraordinarily like that it does so, and we can be certain that risks of diseases of aging (certainly, type 2 diabetes) is reduced significantly.

There are LOTS of sensible reasons not to be on CR. Believing that "it doesn't work" isn't one of them.

[1] Fontana L, Meyer TE, Klein S, Holloszy JO.
"Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans."
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63. Epub 2004 Apr 19.

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Michael Cooper pointed me to the Statsman web site that tracks and displays contribution information for the Folding@Home project. I've been gently encouraging folks to join the Longevity Meme Folding@Home team for a while now, so this seems like a good occasion to remind you all:

Folding@Home is a distributed computing project run under the auspices of the smart guys at the Stanford University Chemistry Department. They rely on the contributions of millions of hours of spare computing time by people like you and I. This processing time is used to solve the hardest, latest and most pressing problems in protein biochemistry.

The understanding gained by the Folding@Home team speeds up the search for therapies and cures for a number of important degenerative conditions of aging. Currently, Alzheimer's is at the head of the list.

...

Join the Longevity Meme Folding@Home team! Competition is a good thing, inspiring us to do better. Our team number is 32461. Enter this in the "Team Number" box when installing Folding@Home. If you are using Windows, you can always update this number and other options by right-clicking on the Folding@Home icon in your system tray and choosing the "Configure..." option.

You can view the Longevity Meme team statistics over at Statsman. Don't let your computer sit idle while not in use - put those extra processing cycles to work advancing our understanding of human biochemistry and age-related conditions!

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Well, I crossed the line into Papal discussion a few days ago, so I may as well go the whole hog and point to comments over at Cyborg Democracy:

On life extension and anti-aging: "Disposing of death is in reality the most radical way of disposing of life."

Glee. I look forward to seeing the justifications underlying that bizarre remark - not that this position is really any different from that held by the previous Pope. Although it has to be said, I'd take these views with more than a grain of salt if their holders didn't tend to cling so tenaciously to life using the best that modern medicine and wealth can buy. The glorification of suffering and death that is so prominently displayed in the Western Christian tradition is, at root, rank hypocrisy. It's all fine and well when it's someone else's suffering and death - but you won't catch a Pope refusing to prolong his own life with advanced medicine.

Fortunately, progress towards better medicine, greater control over our bodies and regenerative cures for age-related conditions seems to be happening despite the destructive wishes of the Vatican and other like-minded people. It would go faster if they would just make their own choices for themselves and stop trying to force the dire consequences of their worldview down our throats.

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I stumbled across a nice quote from James Vaupel today in a filler piece from The Age:

The Max Planck Institute says medical innovations, a better diet and less risk of sudden death in war or accidents means that every second child born in the industrialised world now has an even chance of living to more than 100.

"But 125, 130 years is not unreasonable to expect soon," said James Vaupel, the institute's expert on ageing. "Really, the potential to live even beyond this time is there."

With more talk of healthy life extension in the media, public support for funding research into longevity therapies will increase. What separates us from much longer healthy lives is a gulf of acceptance, will and funding ... the technology is almost secondary given that the path ahead is so clear.

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Some interesting points are raised in an article I noticed today:

The aging population increase in the US and throughout the developed world appears to correlate with a switch from acute infectious diseases to chronic diseases as the major cause of morbidity and mortality.

Some diseases like ulcers and certain types of cancer, once thought to be primarily related to lifestyle factors, are now known to be caused by microorganisms, and many more syndromes, including some psychiatric conditions, may have a connection to infection.

Scientists propose that much of the (entirely incidental) increase in average and maximum healthy life span over the past century stems from removing the damage done to our bodies by disease over a lifetime. Less disease means less damage - which means a better chance of a longer life according to the reliability theory of aging. This article proposes that medical science has, to date, only managed to deal with the easy half of the disease problem:

Up until the late 20th century, health professionals believed that chronic diseases such as peptic ulcers and cervical cancer were caused in part by lifestyle factors such as diet, stress and exposure to environmental toxins. In the last several decades, researchers have compiled strong evidence that most peptic ulcers are caused by an infection with the bacterium Helicobacter pylori and can be treated with antibiotics. An infection with human papillomavirus (HPV), the cause of genital warts, appears to be the cause of cervical and other cancers.

In addition to H. pylori and HPV, the report lists 30 other microorganisms for which there exists strong evidence of an associated chronic disease. The report also lists over 40 other chronic diseases, including heart disease, Alzheimer's and schizophrenia, which are suspected of having an infectious cause.

Proving causation is difficult. Scientists have traditionally applied a series of tests, known as Koch's postulates, to establish that a specific microorganism does indeed cause the associated disease. Because of the complex nature of chronic illnesses, oftentimes it is not practical or even possible to use Koch's postulates to prove the infectious nature of chronic illness. The report recommends that new criteria for evaluating the strength of association between microbes and chronic illnesses be developed.

The lack of progress to date in more important age-related conditions may be as much a function of the difficulty of identifying a cause as it is a function of these conditions only becoming more prevalent as more people live longer lives.

I point this out as a matter of interest - it is of course still that case that far more progress in healthy life extension can and should be made by directed research into extending the healthy human life span. We do need cures for chronic age-related conditions (infectious agents or not), but a great deal of funding is already invested in that research. Not so for the fight to cure aging, alas.

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Much of the currently funded research into healthy life extension - such as work on calorie restriction biochemistry and mimetics - is focused on manipulating metabolism. This is much akin to fine tuning an engine to get a better mean time to failure; not fixing the underlying problem so much as somewhat reducing the rate at which it causes damage. With that in mind, the healthy life extension community is currently pondering what to make of news that a hibernation state can be induced in mice:

Mark Roth, a biochemist at the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues tried exposing mice to air laced with relatively low concentrations of the gas: within minutes, the mice seemed to fall unconscious. Their core body temperature dropped by some 20ºC, and their breathing slowed from about 120 breaths a minute to fewer than 10, the team reports in Science.

When re-exposed to clean air after six hours, the mice bounced back without any evident side-effects, says Roth. "This indicates that it's possible to decrease metabolic rate on demand," says Roth.

Aside from the obvious uses in surgery and a range of life threatening circumstances, what can be done with this discovery in the arena of extending healthy life spans? That's a good question, but it's worth noting that some folks feel that investigating the biochemistry of large hibernating mammals is very relevant to healthy life extension.

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Rand Simberg ties papal succession (a topic I have to admit I didn't see showing up here) and healthy life extension together in his latest article:

Despite his years, though, they may get a lot more continuity than they bargained for. This is, after all, the twenty-first century, in which technological breakthroughs in general, and medical breakthroughs in particular, are coming along at a breakneck and accelerating pace. Such advances, described in the recent books More Than Human by Ramez Naam, and Joel Garreau's Radical Evolution, may upend (among many other things) the stately applecart of traditional papal successions if (as seems increasingly likely) they result in extreme life extension and indefinitely-long healthy human life spans.

...

In a world of conventional life spans, we can always console ourselves with the thought that, if we're stuck with a dud pope, or a particularly nasty and competent dictator, or an overactivist judge, no one lasts forever.

...

If, as many think, this pope was selected to provide at least a temporary bulwark against modernity, how ironic that one of the features of modern life that he might be having to fight could also be one that could allow his own obstruction to it to be permanent

I think that it's clear that change means change - as and when scientists attain funding enough to build the technologies of radical life extension we will start to see shifts in society to match. I imagine that lifetime positions will be one of the first to go. Large organizations like to maintain the status quo, and the status quo is a certain amount of turnover.

As a side note, I've never found the immortal dictator to be a particularly convincing objection to healthy life extension. For a start, it's also an objection to all modern medicine and its life-prolonging effects. Secondly, how many dictators manage to maintain their position for life at the moment?

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A study on the health risks of being overweight has been in the news of late, as it declares the effect on mortality rates of modest excess weight to be much lower than previously estimated. This sort of news is always received well for all the obvious (and poor) reasons - people like to be told that they aren't doing so badly after all.

Unfortunately, we simply can't take each new study as the last word on any complex topic in science; statistics and human health are certainly both complex topics. The process of scientific investigation, research and debate on any given subject produces an array of papers supporting each major position as the years go by. Only slowly does the preponderance of evidence lean one way or another, and certain answers must wait for a complete understanding of the underlying processes and factors involved.

I have opined before on the merits of being a conservative late adopter in matters relating to healthy and healthy life extension; the points are still valid. A wait and see attitude is a good thing in my book:

Science is a debate aimed at discovering the truth, supported by tested methodologies for determining, reviewing, interpreting and predicting facts. Important questions, especially those related to medicine and statistics, are not answered with a single study. Each study, and the resulting debate, can take years. Building - or changing - even a preliminary scientific consensus on any position is a process that spans decades.

People are hungry for definitive answers. Nobody likes an unanswered or partially answered question, but unanswered questions are the essence of science. All "answers" provided by science are theories, possibly wrong in as-yet undetermined ways, and subject to replacement when a better theory emerges.

So while looking at this latest study on one hand and a plate of donuts on the other, bear in mind that there are still a great many studies out there to demonstrate that even modest excess weight greatly increases the chance of suffering common age-related diseases. A last word from the article linked above:

Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital in Boston, said she is not convinced that the new estimate is right: "It's likely there has been a weakening of the mortality effect due to improved treatments for obesity. But I think this magnitude is surprising and requires corroboration."

Improved treatments or not, it's probably not a good idea to expect medical science to rescue you from the future costs - financial and otherwise - of failing to take care of your health now.

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There is nothing unusual, radical or strange about working towards extending the healthy human life span.

We are forced to rely on a valuable, complex machine - our bodies - in everything that we do. Like all machines, it tends to run down and eventually stop working; the process is unpleasant and we would prefer to make longer and better use of this machine. As for all machines, we can research better means of preventative maintenance and repair. If we can keep a vintage car in good condition for so long as we care to spend resources on it, we can certainly work towards the same capacity for the human body. Complexity is just a matter of degree - there is nothing mystical about cells and genes, no more so than for crankshafts and fan belts. The dividing line is between things we know how to do and things we don't yet know how to do.

Thus healthy life extension is simply common sense; the same common sense you apply to making the most of every other machine in your life. If you don't know how to do it, you learn.

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A little science from sci.life-extension to start the week off on the right foot:

Increasing evidence suggests that mitochondrial function declines during aging in various tissues and in a wide range of organisms. This correlates with an age-dependent large accumulation of specific point mutations in the mtDNA control region that was reported recently in human fibroblast and the skeletal muscle. However, it is rather rare to evaluate aging-related mtDNA mutations in other model animal systems. In this study, we analyzed mtDNA control regions of brain, skeletal muscle, heart, and other tissues from aged mice, in search of specific point mutations.

...

This may suggest that that humans have a better or tighter copy number control. Deletion mutations and clonal expansions occur in in human cells with relaxed copy number control but apparently not normally as in mice . If this is in fact true then this could presumably account for the longer lifespans and decreased ROS of humans in relation to mice.

The commentary is of course speculative (if well informed), but it is always good to see more work being done on mitochondria in the context of aging. Unlike many other areas of aging science, some groups are making headway on the required groundwork for repairing age-related damage in mitochondria.

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I noticed another op-ed column on radical life extension today that, despite a promising start, manages to nicely bracket the common (mistaken) errors and objections regarding longer, healthier lives.

The down side? You get twice as long with that sore hip and arthritis. You must spend more time dealing with the inability to sleep through the night without getting up two or three times to visit the bathroom. You have to listen to several more generations talk about how you screwed up the world. You have to see all those "Murder, She Wrote" episodes over and over and over.

And worst of all, for many people, you have to spend 147 years working for The Man.

That was what I figured would be the biggest hurdle for most people - having to work day after day after day for nearly 15 decades. To work at the factory for 40 years and be just a quarter of the way into your career.

But nearly everyone would do it. What's your take? E-mail me with your feelings - ... bstanhope@dailyrepublic.net

I'd suggest doing your part for healthy life extension advocacy and writing to this fellow to point out the ways in which he gets it wrong - the Tithonus Error for the hips and arthritis; economic misunderstandings relating to savings and retirement; on insinuations of boredom. Wonderful rebuttals for all these points have existed for decades - we need to do a better job of spreading the word.

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I know, I know, I keep giving you folks links to the Mprize multimedia page, but I did say that I would point out the video of Aubrey de Grey's appearance at BIOMEDEX 2005 when it became available. The direct links to the video are:

• RealPlayer Format
• MPEG
• MP3 Audio Only

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President of the Gerontological Society of America, that is. You can find his campaign statement in their latest (PDF-format) newsletter:

In recent years, the biology of aging has become sexy. By that I mean that scientific efforts to understand, and purposely alter, the rate of aging - in animals now, but ultimately in humans - receives an inordinate amount of public attention. Those of us in the field note that it has now become easier to publish our papers in prestigious scientific journals. Our phones ring regularly with inquiries from journalists in both the print and electronic media asking for our interpretations and opinions about new scientific research to be sure, but also about the social, political, and ethical implications of our work.

The dirty truth of it is, of course, that as much as our opinions might be useful in interpreting new biological breakthroughs, most of us have given scant thought to the social, political, or ethical implications of our work. For all of the time we spend at our laboratory bench, we spend little time thinking about the day-to-day life, the personal pleasures, or social roles of the elderly ... which illustrates why the GSA is so vitally important. It is the only organization that routinely brings together people that should be talking to one another across discipline boundaries - caregivers, political scientists, biologists, educators, historians, and philosophers - and forces them to talk to one another. In doing so, it gives form and breadth and context to the work of all of us and makes us consider issues that we might easily avoid by locking ourselves solely in the company of our fellow specialists. I remember the first GSA meeting I attended featured a symposium, organized as I recall by Roy Walford, on the topic of whether it was ethically justifiable to medically retard aging. I was surprised to discover that not everyone considered (as the biologists did) that retarding aging was an unalloyed good thing. Moreover, the reservations expressed were meticulously thought out, clearly and forcefully expressed, and as I later discovered, quite representative of wider public opinion. My horizons were broadened in a way that no number of meetings with other biologists was likely to do.

Steven Austad is a good deal less conservative than many in the GSA when it comes to applying the lessons of aging research to extend the healthy human life span - having a more forward-looking and well known society president would be a positive step forward for the field.

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The full text of the recent New Scientist subscriber-only article "Welcome to the Immortals' Club" is available over at the Transhumantech Yahoo! Group. It's something of an outsider's view into the healthy life extension community and the debate within gerontology - and hence riddled with minor errors and misconceptions - but still worth reading.

De Grey knows he is outside the mainstream but insists he is on the right track. "Most of my colleagues in gerontology do appreciate that ageing in general is not a good idea, but they're completely convinced that nothing can be done about it in the near term," he says. "They're wrong. If I make it to 110, I reckon I'll have at least a 50:50 chance of making it to 1000 and quite possibly much more."

A pity that since it's a subscriber only article, comparatively few people will actually read it.

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The divide between people who instinctively find healthy life extension and longer lives an obvious, wonderful goal and those who do not is an odd one. Speaking as someone who would like to live healthily for a long, long time, I often find pro-aging, pro-death folks downright incomprehensible.

It's always nice to see other people out there in the world who feel the same way:

The promise of extended life spans has never been more truer than today, and it will be even more true tomorrow. The technology is advancing with our understanding of the molecular machinery of the body. Will we have it beat in 25 years? I personally think that might be a bit optimistic, but those of us in my age bracket might be able to expect another twenty or thirty years above the norm, and that might stretch us long enough to see a major breakthrough someday.

Would you be bored by a three hundred year life lived at the biological age of 25? I've never really understood the downside of life extension, or the virtues of death in the face of potential rejuvenation. There will always be a segment of naturalists who will be content with their three score and ten, but it seems to be such a waste. By the time we have things figured out, it is too late to make meaningful change.

...

Either way, I wouldn't understand anyone who would refuse such potential.

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The last third of a Pharmaceutical Business Review article caught my eye; it links the technologies of regenerative medicine with Aubrey de Grey's Strategies for Engineered Negligible Senescence proposals.

One of the more forward looking applications of human cloning research could be a 'cure' for aging, or at least the reduction of its effects and an increase in human longevity. Aubrey de Grey, a leading gerontologist, is a proponent of regenerative medicine, the emerging industry focused on the treatment strategy of replacing malfunctioning cells with fully functioning ones. He suggests a number of ways in which the 'disease' of aging can be stopped, or at least slowed down. One of his theories states that we could prevent age-related cancers by replacing our own stem cells with genetically engineered stem cells in which the genes that encode telomere-elongation are deleted.

These ideas could imply the use of genetic engineering alongside human cloning techniques to develop specific, disease free tissues that could be replaced as necessary. The prospect of human life expectancy extending well into an individual's second century, and maybe beyond, throws up some bizarre questions. A crucial consideration here is not just extending the period at the end of life or drawing out old age, but lengthening people's productive and active lives. Would longer lives mean lower birth rates? Or could we continue to extend our reproductive capacity as well? Furthermore, who would pay for the groundbreaking technology enabling them to live longer? The cost could be prohibitive to all but the wealthy few, meaning the 'haves' can live forever, but where does that leave everyone else?

Interesting - and promising - to now see this sort of discussion cropping up as the logical end to an article on therapeutic cloning, stem cells and regenerative medicine, regardless of the technical merits or accuracy of the piece. The slew of objections to healthy life extension have been addressed here before, needless to say.

(Feel free to critique in the comments, however).

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Leonid Gavrilov recently pointed the GRG list to an interesting discussion on the evolutionary theory of aging - complete with thoughtful comments from the likes of Richard Miller, Steven Austad and Andrzej Bartke.

I cannot imagine any theoretical construct more central to biogerontology than the evolutionary biological theory of aging (SN Austad, Why We Age, Wiley, NY, 1997). The theory applies to age-structured populations and to ecologies that dominated the early history of particular animal species. These early nature-nurture interactions shaped the genomes so that their life histories maximized reproductive fitness. In ecologies with high hazard functions, the more optimal life history would be one that involved rapid development, large numbers of progeny beginning shortly after the attainment of sexual maturity, and relatively short life spans. For the case of low hazard environments, a different life history strategy, one involving slower rates of development, longer periods of fecundity and longer life spans, might prove to lead to greater reproductive fitness. Tom Kirkwood's formulation invokes trade offs between the need for energetic resources for reproduction versus the need for energetic resources to maintain the soma (Kirkwood and Holliday, Proc R Soc Lond Biol Sci 205:531, 1979).

It's well worth a read for those of you who are interested in aging research.

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I'm sure you're familiar with conservatism in the gerontology community with regard to serious anti-aging research; Aubrey de Grey's The Curious Case of the Catatonic Biogerontologists gives a good account of this phenomenon - and what can and should be done about it. How does this conservatism manifest itself in terms of research and funding recommendations, however?

The short answer is that conservative gerontologists call for more efforts to understand aging. More aging research in the current fashion in other words; conversatism manifests itself as a fixation on developing an ever more complete picture of the molecular biochemistry and genetics of the aging process. More knowledge is not a bad thing, but conservative gerontologists are unwilling to admit that current levels of knowledge are sufficient to begin research and development of meaningful healthy life extension therapies - the application of this knowledge.

More forward looking, engineering-based proposals (like Aubrey de Grey's Strategies for Engineered Negligible Senescence initiative) differ by stating that we already know enough to make meaningful inroads into real anti-aging research and the development of therapies to extend healthy life span. This is self-evidently true, as a comparison with any other field of medicine should demonstrate. We don't have a complete understanding of cancer (or almost any other medical condition by gerontological standards of "complete understanding"), yet that hasn't stopped the scientific community from producing ever more effective treatments as our level of knowledge increases.

The road to a cure for aging, like the road to a cure for cancer, has many waystations - each representating some level of treatment, some level of extended healthy life spans. Conservative gerontology ignores the existence of those waystations. Can you imagine a world in which cancer research proceeded that way, pure research with no funding invested in application and the development of therapies?

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Dave Gobel of the Methuselah Foundation drew my attention to a WorldChanging commentary on the rather horrible "The Coming Death Shortage" from the Atlantic. I think that the WorldChanging crew give it more respect than it deserves, but make your own mind up.

I do agree that it is good to see pro-death advocates taking the prospects for radical life extension seriously - no-one with an understanding of the field and the way in which progress happens is laughing at these ideas any more. Healthy life extension is coming; the big question is whether or not it will happen fast enough to benefit those of us reading this today. (And whether enough people will step forward and act to make a difference).

Don't forget to read the comments - many are better than the post in terms of addressing the problems and misconceptions in the reviewed article. Remember that in the end any argument against medical research for longer, healthier lives is an argument for forcing millions of people to suffer and die. It's that simple.

UPDATE: Conveniently enough, you can find the full article text posted at the transhumantech Yahoo! group.

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You may recall Aubrey de Grey's EMBO reports article from last month. Well, you can now download audio, video and a powerpoint of his presentation last year at the 5th EMBO/EMBL Joint Conference on Science, Society, Time and Aging Mechanisms and Meanings from the Mprize website. (You may have to scroll down on that page to see it). You'll also find a number of other interesting video clips from the past year - many thanks go to Kevin Perrott and the other volunteers for putting this all together.

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The most important meme that healthy life extension advocates are currently working to spread runs something like this:

The current aging research establishment is far too conservative regarding the near future potential of fully funded longevity research, and their conservatism is damaging the prospects for this funding. The human body is merely a very complex machine and aging is just another medical condition. Aging can - and should - be addressed just like any other chronic, progressive, fatal medical condition. New technologies and knowledge mean that high levels of funding for directed anti-aging research will produce radical gains in healthy life span quickly enough to benefit those of us reading this today.

Over the mid to long term, greater adoption of this meme and related ideas will mean greater research funding and greater pressure for progress and legitimacy in longevity research. You can see Ray Kurzweil hard at work propagating his version of this meme in recent media appearances.

Scientists believe that in the future people will be living for ever - because they will find the key to eternal life.

They believe death is merely an engineering problem to be solved and are developing an organisation called the Institute of Biomedical Gerontology to find that key.

Futurologist Ray Kurzweil, who predicted the internet would rise to global dominance when it was still an obscure government communications network in the 1980s, says immortality is on the horizon.

To date gerontology has largely been a cautious and conservative field dedicated to understanding the biology of ageing. But the new immortalist movement takes a wholly different perspective.

...

His optimism is based largely on biotechnology showing the kind of exponential progress that created the information technology revolution, New Scientist reports.

...

"We're 20 years away from the golden era of nanotechnology," says Dr Kurzweil. "I didn't just start making predictions yesterday."

Most mainstream gerontologists, however, are circumspect. "Research on the biology and genetics of ageing is currently at a similar state to cancer research 20 years ago," says Dr Howard Jacobs, a geneticist at the University of Tampere, Finland.

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Biogerontologist Aubrey de Grey recently recorded a debate on the prospects for radical life extension at the Edinburgh International Science Festival. It is currently available as an audio stream from BBC Scotland - get thee hence and listen.

UPDATE: Kevin Perrott has made an MP3 version available for download at the Mprize website.

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An article at Forbes takes a look at the effects of wealth on longevity, finding that a) it doesn't make much of a difference in the grand scheme of things and b) any meaningful analysis would have to take into account the host of selection effects. If you're smart and driven enough to get rich, you're probably also someone who takes care of your health.

The billionaires lived 3.5 years longer than average American males. The results would be even more dramatic if we took into account average life expectancies from around the world, since the billionaires on our list are of all different nationalities.

According to a 1999 study in the British Medical Journal, higher income is, in fact, "casually associated with greater longevity." But when it comes to living longer, billionaires may not be that much better off than mere millionaires. "While an extra dollar of income is protective," the study reads, "the amount of protective effect tails off as total income rises."

...

Some studies contend that rich live longer because of intellectual Darwinism. "Social status," Seligman writes, "correlates strongly and positively with IQ and other measures of intelligence, and intelligence correlates strongly with health literacy--the ability to understand and follow a prescription for disease prevention and treatment." This theory is not without evidence: Seligman cites a 2003 study by psychologist Ian Deary of the University of Edinburgh that found mortality rates to be 17% higher for each 15-point falloff in IQ.

Since most of what kills Americans today is chronic disease, health literacy may, in fact, be a key to longevity. Understanding and monitoring risk factors for the major conditions that predispose us to death--heart disease, cancer, diabetes, obesity, high blood pressure--requires a considerable amount of awareness, discipline and foresight.

In any case, simply having great wealth is not going to work wonders for your life span. You'll get a few extra years at most if all you are doing is enjoying the peripheral benefits. One of the hallmarks of this modern world is that the gap in consumer benefits enjoyed by the wealthy and the poor is not as large as you might think, nor as large as it once was. All the advances that would amaze a time traveller from the 1300s are largely available to the first world poor of our time.

There is one thing that wealth does bring, however, and that is the ability to effect change. Wealth is a big lever that can be used to shape the future - it would only take a small fraction of the holdings of the wealthiest 400 people in the world to set serious anti-aging research underway, for example. In other words, the best way to turn wealth into extra healthy years is to fund advances into working anti-aging and longevity medicine rather than simply enjoy the best medicine currently available. One of the goals of healthy life extension advocacy is to make that point clear to the wealthy of the world.

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The comparatively long length of the human life span (nowhere near long enough if you ask me, but a good deal longer than other mammals of similar size and weight) poses an interesting problem for evolutionary biologists. You can get a flavor of current thinking on this issue from a recent Tom Kirkwood paper:

Evolutionary considerations suggest aging is caused not by active gene programming but by evolved limitations in somatic maintenance, resulting in a build-up of damage. Ecological factors such as hazard rates and food availability influence the trade-offs between investing in growth, reproduction, and somatic survival, explaining why species evolved different life spans and why aging rate can sometimes be altered, for example, by dietary restriction. To understand the cell and molecular basis of aging is to unravel the multiplicity of mechanisms causing damage to accumulate and the complex array of systems working to keep damage at bay.

So how, we might ask, did humans end up with long life spans? One set of theories revolves around selection effects that stem from the benefits of socialization and society.

Details of how longevity increases over the course of human evolution provides a wealth of information on how human social networks developed.

The number of people living to older adulthood would have allowed early modern humans to pass down specialized knowledge from one generation to another.

Old age would have also promoted population growth and strengthened social relationships and kinship bonds.

One fairly detailed theory is known as the Grandmother Hypothesis - that prolonged lifespan has been selected to increase the reproductive success of offspring. In other words, the ability to help your grandchildren do well is the driving selection mechanism, not the ability to help your children do well. Enough thought has gone into this for an entire book, it seems:

Darwinian theory holds that a successful life is measured in terms of reproduction. How is it, then, that a woman's lifespan can greatly exceed her childbearing and childrearing years? Is this phenomenon simply a byproduct of improved standards of living, or do older women - grandmothers in particular - play a measurable role in increasing their family members' biological success?

Until now, these questions have not been examined in a thorough and comprehensive manner. Bringing together theoretical and empirical work by internationally recognized scholars in anthropology, psychology, ethnography, and the social sciences, Grandmotherhood explores the evolutionary purpose and possibilities of female post-generative life.

While I'm not sure than any of this directly bears on strategies for extending the healthy human life span via improved medicine, it is interesting.

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I've directed a fair amount of the focus of the Longevity Meme and Fight Aging! towards stem cell research and related regenerative medicine over the past few years. It has been the largest and most obvious battle over freedom of research, a topic I think is very important for long term progress. In addition, stem cell technologies will help - directly or indirectly - to extend healthy life span in the years ahead. Cures for common age-related diseases are the direct approach, though this is not as helpful as you might think from the point of view of extending maximum life span. Any number of other age-related conditions lurk, waiting to be discovered as our life spans grow longer. Cures for cancer, diabetes, Alzheimer's and so forth will add years for those who would have suffered and died, but don't do much to the underlying processes of aging that limit our maximum life span.

The knowledge we gain regarding the biochemical and genetic workings of our cells in the course of stem cell research is pure gold - it will speed, assist and enable all sorts of research into finding and addressing the mechanisms of the aging process. We don't want to find out (the hard way) about new age-related conditions that lie beyond Alzheimer's. Rather, we want to learn to halt the aging process in its tracks; prevent degeneration and damage or repair it as it happens so that we don't have to devise ever more complex strategies to deal with the end results of aging.

But back to the battle over stem cell research: think it's safe to say that we're over the hump. Most people are aware of (and comparatively well educated about) the benefits of stem cell research, funding is widely supported and anti-research legislation opposed. There were only a few noteworthy advocates a few years ago - now there are well-organized hundreds ... and news sites, blogs, press attention and all that goes with it. The battle continues, but I think that anti-research groups have as good as lost - the forces arrayed against them are too strong; it is human nature to grasp at new medicine with both hands once the benefits are clear. The worst that the anti-research groups can do is to continue to delay the development of stem cell based therapies for age-related conditions - a little here, a little there.

Overall, this means that I will be spending more time in the future on aging and longevity rather than stem cells - unless there is direct relevance. Stem cell research and advocacy is well underway, but serious anti-aging research is not. However well things are going elsewhere in the world of medicine, that remains a big problem.

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A little science coverage relating to calorie restriction mimetics today for those of you who like to keep a close eye on such things; this post was made by Pete Estrep on the Gerontology Research Group list:

I'm not sure how tuned in to the Sirtuin/resveratrol controversy GRG members are (I know some eavesdroppers/lurkers know the scoop) but this is turning into the biggest head scratcher in aging research. Here are the basics. While in Lenny Guarente's lab at MIT, Longenity co-founder Matt Kaeberlein discovered the life extension effects in yeast of a protein called Sir2. Guarente's lab showed that Sir2 is a NAD-dependent deacetylase and Guarente and Heidi Tissenbaum showed lifespan extension of nematodes overexpressing Sir2. Several labs, including Guarente's and Dave Sinclair's at Harvard went on to show that Sir2 has several interesting properties. Some of the most interesting research has come from a collaboration between Sinclair's lab and BIOMOL Research Laboratories in Pennsylvania, the makers of in vitro assay products for Sirtuin activity. Using the BIOMOL assay several Sirtuin Activating Compounds (STACs) have been identified, one of which is resveratrol. Sinclair showed that resveratrol increases yeast replicative lifespan, and then together with Marc Tatar and Steve Helfand, they showed that resveratrol extends lifespan in nematodes and fruitflies. Resveratrol looks very exciting, right? Well, things have gotten interesting in the past few months.

Matt Kaeberlein, who is now back in academia at the University of Washington, recently published two papers with Brian Kennedy and Stan Fields. One shows that the lifespan-extending effects of Sir2 in yeast are strain dependent, that calorie restriction of yeast extends lifespan more than Sir2 overexpression, and that this effect is Sir2 independent.

The more recent publication shows that the in vitro assay used to assay Sir2 function is faulty, that resveratrol activation of Sir2 is an artifact, and that resveratrol has no effect on Sir2 activity in vivo, as measured by rDNA recombination, transcriptional silencing near telomeres, and replicative lifespan (Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell S, Napper A, Curtis R, Distefano PS, Fields S, Bedalov A, Kennedy BK. Substrate specific activation of sirtuins by resveratrol. J Biol Chem. 2005 Jan 31; [Epub ahead of print] PMID: 15684413. The in vitro artifact has been confirmed by another group at the University of Wisconsin ( Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol .J .Biol Chem. 2005 Mar 4.). So, at least three groups have shown lifespan extension by resveratrol in yeast, worms, and flies, and it is claimed that resveratrol is acting by binding to and directly activating Sir2; and now two groups have shown that this binding is an artifact and Kaeberlein and colleagues have shown that the lifespan extension also appears to be an artifact.

Now, to further complicate things, Parker and colleagues (Parker, J. et al. Nat. Genet. 37, 349-350 (2005) have presented data suggesting that resveratrol moderates the symptoms and is neuroprotective in two models of Huntington's disease, and this effect is Sir2 dependent. Are you confused yet? Me too, along with everyone else in the field. Stay tuned for new developments.

While I'm not voting this "biggest head scratcher" (that would be reserved for why serious longevity research is so underfunded), it is certainly interesting. It seems that research groups are on the verge of pulling the various threads together - this sort of confusion and contradiction is very indicative of progress in science. A more accurate picture of this facet of our metabolic processes and its interaction with healthy life span can only be beneficial. It is plausible that we could obtain an extra decade or two of additional healthy life span from the application of modern biotechnology to improving our metabolism. This may not be radical life extension, but it is certainly better than nothing.

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I am compelled to direct your attention to yet another entertaining high-quality post from Methuselah Foundation fundraiser and calorie restriction practitioner April Smith.

So I was expecting to walk up to Jay Olshansky after the debate and start a happy chat about how much better everything would be if lots and lots of people would do at least moderate CR. I pointed out that CR will get us most of the benefits he outlines in his three goals, and that Luigi Fontana is studying CR'd humans and finding excellent health results. ... Dr. Olshansky then said, "But what you're on is an experimental diet."

"So is whatever you ate today," I answered.

As you might have gathered, April has been at the BIOMEDEX show alongside Aubrey de Grey to talk up the Mprize for anti-aging research. I eagerly await video and transcripts of the debate between de Grey and Olshansky...

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