Biomedical gerontologist and radical life extension advocate Aubrey de Grey will be continuing his winter of conference appearances - after the Immortality Institute conference this coming weekend - by presenting at NEXT05 on November 25th 2005, at the IT University of Copenhagen, Denmark. You can find the program of speakers at the NEXT05 website, and I highly recommend you take the chance to hear de Grey speak if you are in the vicinity.

To get up to speed on de Grey's work and the case for major research projects aimed at extending the healthy human life span, you might want to start with the introduction to the Strategies for Engineered Negligible Senescence (SENS) at the Longevity Meme and move on to read through the SENS website:

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

...

the engineering (SENS) strategy is not to interfere with metabolism per se, but to repair or obviate the accumulating damage and thereby indefinitely postpone the age at which it reaches pathogenic levels. This is practical because it avoids both of the problems with the other approaches: it sidesteps our ignorance of metabolism (because it does not attempt to interfere with metabolic processes and their production of side-effects) but also it pre-empts the chaos of pathology (because it repairs the precursors of pathology, rather than addressing the pathology head-on).

Technorati tags: conference, life extension, SENS

Posted by Reason at 7:33 PM
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I had an interesting discussion yesterday with someone we shall describe, for the sake of brevity, as an investment scout for a venture fund. It was reassuring to see - once again - that the venture investment community, like other communities, has its share of pro-healthy life extension members. Like many of us, the scout wonders how best to speed progress towards longer, healthier lives within the present set of working constraints.

All in all, it was a good counterpoint to my personal focus on modern science and its many-faced relationships with the goal of extending the healthy human life span. I tend to move my attention away from areas in which there is a great deal of momentum and support - cancer research, or stem cell research in the past year, for example. My activities as a commentator and advocate would be largely superfluous for these branches of science, and certainly less effective than larger and more practiced groups. (I'm still eagerly awaiting this state of affairs to transpire for healthy life extension research - I'll be delighted to see more individuals and groups out there doing a better job than I am ... and yes, that was a challenge). For the investment scout, however, fields with momentum are the most promising; they generate more early stage companies and more successful later stage investment opportunities. In contrast, a field without momentum is probably at least five years from commecialization, it it heads that way at all - hence not all that interesting to most private investors because they have other, more rapidly maturing opportunities to choose from.

Giving high level venture investment advice is just common sense based on an extrapolation of what you know (and what you know about your own level of knowledge; anyone can give an opinion, but how useful is it?). Imagine yourself with $10 million and the constraint that you have to aim at a good rate of return - what fields would you invest in? The rate of return requirement immediately rules out most of the uses I would normally come up with, but I'm biased towards philanthropic approaches to early stage advocacy and education in healthy life extension - which may also go some way towards explaining why I must imagine my hypothetical investment money. In any case, here are my thoughts in brief:

• Commercialization of stem cell research is the obvious area of investment, whether in the US or not. It is a very active field, clearly going to bring enormous benefits to patients, advances our knowledge of cellular biochemistry and processes - which is a very good thing in and of itself - and addresses the first of the seven pillars of SENS.

• Companies working on calorie restriction mimetics and related forms of metabolic tinkering are currently a viable choice for investment, but I wouldn't choose to put money into this area. I think it's helpful work - which adds useful knowledge about our cellular processes, just like stem cell research - but it's just a stepping stone. Unlike stem cell research, it's also much less effective as a late-life therapy; to get the best benefit from a metabolic tweak, you would have to have it your entire life.

• Therapies based on repair or replacement of mitochondria will be hot in the next few years - the science is close to commercialization for at least one or two teams. A number of age-related diseases can plausibly be targeted by these therapies, allowing an approach through FDA and other regulatory hurdles, and they address another of the forms of age-related cellular damage noted in the Strategies for Engineered Negligible Senescence.

• Companies presently making the tools for the next generation of nanotechnology are a good investment if you want short term returns and long-term effects. The tools of non-medical ("dry") nanotechnology are in demand for present applications, but will be increasingly used as the basis for medical ("wet") nanotechnology over the next ten years. Bioinformatics, biotechnology and nanotechnology will converge to form the new discipline of nanomedicine - something a good deal more impressive than the drug delivery and diagnostics work that currently goes by that name. This convergence will be accomplished by groups who find ways to use the tools of dry nanotechnology to build truly advanced nanomedical applications, such as mass-produced nanomedical robots or superior artifical blood cells.
  

Technorati tags: investment, life extension, venture capital

Posted by Reason at 3:10 PM
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Some interesting news has surfaced from researchers working on uncovering the mechanisms of life extension through calorie restriction. From the Gerontology Research Group list (and via the transhumantech group) we have this:

Flachsbart and colleagues are reporting in Experimental Gerontology the result of a study many of us have been hoping to see. They assayed SNPs of SIRT1 in 1573 long-lived individuals (LLI) and find there is no association between longevity and any tested SIRT1 polymorphism or haplogroup. This does not rule out the possibility that lifespan-extending biochemistry or regimens (such as calorie restriction) might be acting through a separate pathway/mechanism in humans, as in yeast (reported by Kaeberlein and colleagues), or through another one of the other six sirtuins in humans. Consistent with this hypothesis Rose and colleagues have reported a weak association between polymorphisms of SIRT3 and male but not female longevity. This is unexpected since SIRT1 is probably the closer functional homologue of yeast Sir2 and C. elegans Sir 2.1 (since it is active in the nucleus and SIRT3 is active in mitochondria), and evidence has been pointing to SIRT1 being a regulator of lifespan in rodents. SIRT6 and SIRT7 might be even closer functional homologues to Sir2 since they are similarly localized within the cell: in heterochromatin and nucleoli. Association studies are probably underway for these two. Stay tuned.

The devil is in the details, as usual. As scientists close in on what makes calorie restriction work in humans, we may see calorie restriction mimetic drugs or therapies capable of reproducing modestly beneficial effects on metabolism and life span. As always, it should be noted that these sorts of metabolic tinkering are not the pathway to radical life extension - even if they work out, they are just a stepping stone to more effective anti-aging therapies capable of reversing age-related cellular damage.

Technorati tags: biotechnology, calorie restriction

Posted by Reason at 1:49 PM
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Is life good? Is being alive to find out a good thing? Is preventing suffering and death just as good? Does a value judgement even matter? Some people, when presented with the obvious moral imperative to healthy life extension, are apparently hazy on the answers:

I'm also not going to argue that extending the human life span is a bad thing. What I am going to do, though, is demand that some argument be put forth that it is a good thing.

This is only to be expected, I suppose, in a varied world that includes attitudes like those put forward by Leon Kass or similarly minded folk. Yet it never ceases to amaze me that people require a justification for individual choice. Make no mistake, choice is precisely what the future of healthy life extension is all about; it is the creation of a choice - whether to age, whether to suffer, whether to die - where no choice previously existed. In this respect progress towards real, working anti-aging medicine is no different from every other aspect of technological progress - we are all transhumanists, expanding the bounds of the possible, discarding bad old limitations.

There should never be any argument over whether people can collaborate to make a choice for their own lives and bodies - the most basic of property rights, the necessary foundation of a truly free society - and there needs to be no further justification than "we want to and we are capable."

Technorati tags: bioethics, libertarian, life extension

Posted by Reason at 9:44 PM
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I've talked about Dr. Weil's current advertising blitz and his aging apologism fairly recently. The topic seems worthy of more discussion, in light of position statements like this:

Weil calls anti-aging advocates "false prophets who are putting out a message that aging is reversible or that we can stop it."

"I think those are very wrong ideas," he says during a recent interview at his Vail ranch, about 30 miles southeast of Tucson. "Aging is a universal natural process, and I think if you set yourself up in opposition to it, you're in a very wrong relationship with nature."

Anthrax is completely natural too, but I'm sure Dr. Weil isn't so accepting of that - or maybe he would be if modern science didn't have it under control. Living in caves and dying at age twenty due to parasites and disease is also absolutely the natural human condition - everything from shaped sticks and controlled fire onwards is not. Arguments to nature are a very bad way to support any point of view in this modern age, and especially points of view that advocate the avoidable suffering and death of billions of people over the course of future decades.

We cannot presently make major inroads in the fight against age-related degeneration; there is no such thing as a proven therapy prevent or repair age-related damage and thus extend healthy life span by decades. Yet. (Although it is certainly the case that you can make decades of difference one way or another to your eventual life span through choice of life style and preventative health strategies). Dr. Weil is in a position in which it benefits his bottom line to claim that anti-aging medicine is impossible, since his business is competing with the reputable and less reputable arms of the anti-aging industry. However, he also benefits from completely ignoring or disparaging the growing scientific consensus that aging is reversible and can be defeated in the future - he's selling to customers in the here and now and certainly wouldn't thrive if they all donated that same money to real healthy life extension research or the Mprize for anti-aging research.

So don't listen to the Dr. Weils of the world. They may be well-meaning, but they're still trying to get you to give up, lie down and die rather than seize the endless possibilities offered by the future of healthy life extension medicine.

Technorati tags: aging, anti-aging, life extension

Posted by Reason at 7:52 PM
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I'm not exactly an advocate of metabolic tinkering as anything more than a stop-gap measure for healthy life extension research - in absence of anything better in the immediate pipeline. It's quite unclear as to the sort of extension of life span you could engineer in humans or other primates simply by tweaking metabolic controls, even though a 50% increase in life span with minimal side effects seems like a very reasonable near future goal for mouse studies these days. Arguments over the effectiveness of calorie restriction on life span in humans could equally be extended to other methods of metabolic control, for example. If we could even manage a decade or two in humans via these methodologies, with a nice reliable technology platform to back it up, that would be great - but I don't think we should be devoting all our resources to metabolic manipulation. It just doesn't have much of a future beyond this optimization, and we want to see much larger gains in healthy life span. To achieve those gains, we have to move beyond optimizing metabolism into repairing or preventing age-related cellular damage or more advanced technologies.

With that all said, however, it's nice to see that research groups armed with modern biotechnology are up to delivering a continual stream of information regarding the mechanisms of metabolism and longevity. From the latest interesting research:

The longevity-promoting effect of reducing CLK-1 activity that was initially observed in C. elegans is conserved in three different genetic backgrounds of mice. In 129Sv/JxBalb/c mice for instance, reducing activity of the gene mclk1 (mouse clk-1) results in a prolongation of lifespan of about 32%. The inactivation of mclk1 gene, which encodes a mitochondrial enzyme, decreases reactive oxygen species (ROS) levels, the toxic molecules that damage proteins, lipids and DNA, and this likely explains this increase in lifespan.

Commenting on his study, Professor Siegfried Hekimi said: "Increased lifespan can be considered a marker for a physiological condition in which oxidative stress is reduced. Extrapolated to the pathophysiology of human diseases partially decreasing CLK-1 activity by pharmacological means should limit oxidative stress and consequently, prevent or slow the development of common age-related degenerative diseases such as Alzheimer's disease, Parkinson's disease or atherosclerosis. Such new therapies may also be beneficial to treat more acute diseases where oxidative stress is also significantly increased such as ischemia-reperfusion injury."

It's both amusing and saddening to watch commentaries such as the one above completely avoid any mention of human healthy life extension even in circumstances where you would think it was unavoidable. This is the atmosphere in which modern gerontology takes place; age-related disease is bad, but no-one must ever say anything about extending life spans.

A life extension of 32% is a good figure for mice - it's in the same ballpark as other life-extending genetic tweaks thought to work by reducing free radical populations. Or calorie restriction for that matter. As always, I eagerly await studies of the healthy life span of mice that possess all of the presently known life-extending genetic modifications.

Technorati tags: life extension, science

Posted by Reason at 8:37 PM
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An update to the $20,000 Strategies for Engineered Negligible Senescence (SENS) Challenge can be found at MIT Technology Review editor Jason Pontin's blog:

Contrary to Mr. Bartlett's story, we have received a number of interesting responses to the challenge - and a group of biologists is, I know, preparing a large, detailed critique of SENS. We still lack a review panel, however, who will review the critiques.

Good to hear that progress is being made; we all win when the research community comes forth to engage in scientific debate on the points, merits and problems of SENS - as it has largely avoided doing to date. Open, honest debate is how we move forward in the process of gaining support for the development of real, working anti-aging medicine - by putting more minds to work on developing the best possible selection of paths forward and persuading more scientists and funding organizations to get the research done.

Pontin also makes a helpful clarification to the SENS Challenge rules:

The full text of any critique can be of any number of words, but any submission should include an abstract of 750 words. In fact, that had always been the spirit of the Challenge ("The form of the submission must be a core document of no more than 750 words, although additional footnotes, citations, and references can be of any length"), but I was perhaps less than clear in my expression.

A substantiative critique of SENS on merits and points of science is exactly the sort of step forward that this challenge is designed to elicit if it is in fact met. Having researchers discussing SENS on the record allows advocates of directed healthy life extension research the open scientific debate they want. The desired end result is a clear, rapid path to working anti-aging medicine that is supported by a large portion of the scientific community, whether it be SENS, a revised version of SENS, or something completely different.

Technorati tags: science, SENS

Posted by Reason at 1:01 AM
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The long Chronicle of Higher Education article on biomedical gerontologist Aubrey de Grey and his tireless efforts to speed the development of working anti-aging medicine is a good read. I recommended forwarding the link to all the healthy life extension skeptics and wavering supporters in your address book. Here are some of the better quotes:

de Grey is a serious, thoughtful, sincere, prolific, even brilliant researcher and thinker who seems to have devoted every last ounce of his intellect to conquering the single biggest medical menace facing mankind. Along the way, he has acquired plenty of supporters and detractors — and gained the respect of some of the top scientists in the world.

...

It may seem surprising that someone of Dr. Atala's stature was a featured speaker at an on-the-fringe conference. Although he declines to pass judgment on Mr. de Grey's more-extreme prognostications, he clearly respects him. "Aubrey is highly visionary and very selfless in his approach," Dr. Atala says. "It takes people like Aubrey to say 'Hey, look at this again. Maybe there is another way to do this.'"

...

Perhaps the biggest celebrity at the conference was Woo Suk Hwang, a South Korean researcher who has shocked the scientific world in the last few years with his laboratory's achievements. ... And yet there he was [at SENS 2], along with dozens of other well-regarded scientists who study anticancer therapies, immune-system disorders, or cellular aging. There were also less-mainstream researchers who look at topics like how to preserve tissue cryogenically. It was a strange hodgepodge of scientists who would probably never meet otherwise.

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In 1995, after having absorbed a great deal of genetics, Mr. de Grey moved on to gerontology, a subject that had always intrigued him. For two months he immersed himself in the literature. He emerged with an insight into the mechanics of mitochondrial mutations, wrote a paper on what he thought, and submitted it to a respected journal.

It was accepted. He was off to a good start.

...

"Aubrey's always arguing against people who tell him he's crazy," says Graham Pawelec, a professor of experimental immunology at the University of Tübingen in Germany. "I have never heard him lose an argument." ... "In 10 years, we will have proof that we can cure these seven things and therefore beat aging," says Mr. Pawelec, who spoke at the conference on "immunorejuvenation" in the elderly. "All of my mainstream colleagues will be up there saying Aubrey was right. And then the general public will believe it."

...

"There are people who say that if Aubrey says it must be right then it must be wrong." At the same time, despite his criticism, Mr. Finkelstein has some appreciation for Mr. de Grey's role as provocateur. "I like him," he says. "He ruffles feathers. He has the balls to say stuff."

The question is whether that stuff will prove to be true. Gregory M. Fahy, a biologist and vice president and chief scientific officer of 21st Century Medicine, a biomedical research company, was very skeptical at first. While they still do not agree on everything, Mr. Fahy has been largely won over. And, like Mr. Finkelstein, he respects Mr. de Grey for his courage in the face of ridicule. "If you think you're right, you have to stand up and say what you believe even if people think you're nuts," says Mr. Fahy. "Now, if they prove you're nuts, you have to shut up. But that hasn't happened yet."

On Tuesday November 1st at 1pm EST, the Chronicle will be holding a live, online discussion with Aubrey de Grey. Mark your calendars!

Technorati tags: life extension, science, SENS

Posted by Reason at 1:11 PM
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Is there such a thing as centenarian envy? Do many people read articles about gung-ho, active centenarians and scheme on how to do just as well in later life? I suspect envy could be a powerful motivator in this case, especially now that the mainstream media has come into the habit of linking centenarians with aging and longevity research:

Right now, most Americans say they don't want to live that long. A USA TODAY/ABC News Poll of 1,000 adults released today shows that Americans, on average, would like to live to be 87 years old, up from the current life span of nearly 78. Just a quarter of the people who responded to the poll said they want to live to be 100 or older.

If researchers could make it possible to live to 120, most Americans would take a pass. Their reasons: Most worry that they'll become disabled by health problems and end up being a burden to their families.

But old age, as Murray illustrates, doesn't always translate to disability or even disease. And scientists already have made some progress toward provocative, futuristic therapies that would slow the aging process itself.

Research by Richard Weindruch at the University of Wisconsin-Madison and others, for example, suggests that an extremely low-calorie diet, one right on the edge of starvation, pushes the life span of mice and other animals to an extreme. If people get the same benefit, some might live beyond 120, about the longest the human body is thought to be able to last today.

Other advances on the horizon include genetic research to identify those genes that might one day protect people from heart disease and other age-related killers.

The National Human Genome Research Institute, one of the National Institutes of Health, last week announced plans to use its gene-sequencing capabilities to search for the genetic roots of diseases that have long eluded scientists.

And scientists at the University of Utah and other research institutions believe that telomeres - long segments of repeated "junk" DNA on the ends of chromosomes - might hold the same key to human longevity that they do to the life of an individual cell. The Utah team linked shortened telomeres to higher death rates from heart disease and infections, speculating that telomere-lengthening drugs could add years to a human life.

Attitudes towards aging and living longer are very shaped by the Tithonus error, as the survey mentioned above demonstrates - far too many people have no enthusiasm for healthy life extension precisely because they think it that a longer life necessarily means more infirmity and disease. Nothing could be further from the case, of course; all successful efforts to repair or prevent age-related cellular damage will contribute to extending your healthy years and postponing age-related degeneration.

Can centenarian envy overcome the widespread Tithonus error in popular culture, leading to greater support for healthy life extension research and a future of legitimate, working anti-aging medical technology? We can hope so - and it certainly can't hurt to see more of this sort of article in the press.

Technorati tags: advocacy, aging, anti-aging, life extension

Posted by Reason at 8:05 PM
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A recent study on the life expectancy and mortality rate of people retiring at different ages shows some correlation between continuing to work and longer life:

Researchers have disproved the theory that people who take early retirement enjoy longer lives as a result. In fact, those who stop working at 55 have nearly double the death rate of those who continue to work on until they reach 65, a study suggests.

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Poorer health forcing some to retire early may be a factor, say the authors.

...

However, this would not entirely explain the differences they found, neither would factors such as sex and socioeconomic status.

Of interest are the effects on health and longevity not already accounted for by existing poor health forcing an early retirement. It's entirely possible that the study authors failed to account for more subtle effects of individual rates of age-related degeneration leading to a retirement decision, but it seems equally likely that "use it or lose it" effects are taking place, both physically and mentally. Stay working, and you are more likely to benefit from whatever exertions you are making in the course of your employment.

Enforced retirement ages in many countries are already quite clearly a monsterous, unethical consequence of entitlement and wealth transfer schemes - and the dangerous mindset of positive rights and enumerated freedoms underlying it all.

There is an even bigger issue here, and it concerns nothing less than the essence of liberty. It is best brought out by considering the distinction, originally due to the British philosopher Isaiah Berlin, between negative and positive freedoms. A negative freedom is a freedom from, whereas a positive freedom is a freedom to. For instance, freedom from being forced to get your neighbor ice cream is a negative freedom; freedom to get your neighbor ice cream is a positive freedom.

In the liberal-political tradition, the essence of liberty consists in an open-ended horizon of negative freedoms. Man is deemed free to do as he pleases as long as he does not infringe on the (equally valued) liberty of others. By contrast, in the socialist tradition, a man's liberty is conceived as essentially a bundle of positive freedoms. We are free to do whatever the government allows us to do. The government may make generous allowances, but unless it does, we have no freedoms we can rightfully call our own.

I don't think that we need any further utilitarian justifications for their abolishment to make the case. If you are willing to work, how is it in any way right and proper for you to be prevented from doing so by government employees?

Technorati tags: libertarian, longevity, retirement

Posted by Reason at 1:07 PM
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The latest edition of Better All The Time from the Speculist gives an enthusiastic nod to the Mprize for anti-aging research:

Read it again carefully: When aging in mice is shown to be 'treatable' the funding necessary for a full-line assault on the aging process will be made available. That means that right now there is almost $2 million in prize money waiting to be awarded to the scientist who figures out the best way to make you live longer.

Research prizes work - that's a soundly demonstrated truth. Harness the human urge to competition, and great things can be achieved. Our hope is that the Mprize will do for serious anti-aging research what the X Prize has accomplished for the private aerospace industry: invigoration, legitimacy, increased funding, and a base on which to grow.

A great deal of work remains in the scientific quest for therapies capable of repairing the cellular damage caused by aging - and the longer it takes, the worse off we all are. If you are prepared to invest money for your financial future, and few of us are not, then you should certainly consider donating to the Mprize to help ensure that future biomedical science can provide you with a longer, healthier life!

Technorati tags: activism, anti-aging, life extension

Posted by Reason at 8:56 PM
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There has been a flurry of promising news and progress of late in the fields of stem cell research and regenerative medicine. This is a good thing, needless to say; visible progress towards cures for many presently fatal age-related conditions is very welcome. As the Strategies for Engineering Negligible Senescence (SENS) remind us, however, even the mature regenerative medicine of ten or twenty years in our future will only provide part of a solution to age-related degeneration. Loss of functional tissue - the problem solved by regenerative therapies - is only one of the seven general classes of age-related damage outlined in SENS.

Technorati tags: regenerative medicine, SENS, stem cell research

Posted by Reason at 10:28 PM
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By way of a reminder, the 13th Foresight Conference on Advanced Nanotechnology will be starting this weekend in San Francisco. If you look at the program, you'll see that biomedical gerontologist Aubrey de Grey is speaking this Saturday and Sunday on the use of nanotechnology in the future of healthy life extension. The event is also a chance to hear Ralph Merkle discuss the nuts and bolts of advanced nanomedicine.

You'll find much more on this topic over at the Longevity Meme and in the Fight Aging! archives.

UPDATE: You'll find a timely interview with Christine Peterson of the Foresight Nanotech Institute over at the Speculist.

Technorati tags: conference, life extension, nanomedicine, nanotechnology