Aubrey de Grey at NEXT05, November 25th
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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).

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Nitric Oxide Again, Alzheimer's
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Nitric oxide production may be linked with longevity in calorie restricted mice, but it's not good in the brain: "An enzyme [iNOS] that triggers the production of nitric oxide (NO) - a gas that helps immune cells fight off invading pathogens - accelerates the formation of brain lesions in Alzheimer's-prone mice ... For nearly a decade, researchers have known that iNOS was present in the brain lesions of patients with Alzheimer's disease, but nobody had addressed whether its presence was making the disease worse. Nathan and colleagues now show that Alzheimer's-prone mice that lack iNOS live twice as long and develop fewer brain lesions than iNOS-expressing mice." Biochemistry is a complicated business, but snapshots like this fail to show the bigger picture: roiling, energetic progress in understanding and knowledge.

Link: http://www.eurekalert.org/pub_releases/2005-10/joem-gms102005.php

On Relinquishment
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There are days on which I can't help but feel that advocates for technology relinquishment really don't think that life is a good thing. This AlwaysOn piece runs through a litany of wonderous advances for the future, building upon progress in medical nanotechnology - such as radical life extension, complete health and even physical immortality - and then tries to convince us that it's all a crock, that somehow we'll suffer more through experiencing change and progress than we would through disease, infirmity and death. There is no shortage of bioethical nonsense in the world; why are these people so eager to ensure that everyone suffers and dies on a schedule that gives them comfort?

Link: http://www.alwayson-network.com/comments.php?id=12607_0_32_0_C

Imminst Conference This Weekend
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The Immortality Institute conference will be held this coming Saturday, November 5th in downtown Atlanta. The full day event will focus on the human brain and life extension. The speakers - including biomedical gerontologist Aubrey de Grey, researcher Michael Rose and scientist Ralph Merkle - will present advanced ideas and methods in anti-aging, artificial intelligence, cryonics, brain-computer interfacing and more. Awards for the Immortality Institute's Essay Contest, The Oblivion Question, will be presented. The Institute's film, Exploring Life Extension, based on interviews conducted across the length and breadth of the healthy life extension community, will be shown for the first time at the conference.

Link: http://www.imminst.org/conference/

Growth Hormone Furor
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(From ScienceDaily). The latest upset in the "anti-aging" marketplace revolves around the legality of growth hormone treatments. You'll hear much light and noise from all sides, so let's just cut to the chase: people should be free to do whatever they like to their own bodies, provided they take responsibility for the consequences. Growth hormone therapies appear to be helpful for some people under some circumstances, but the level of scientific backing for general use that I'd be comfortable with is not there (unlike for, say, calorie restriction). Like many present day therapies, in this era prior to widely available personalized medicine, it's pulling the big red lever and hoping for the best. Results and side effects vary widely, and there are many voices out there making money from hyped, false claims. But none of that is grounds for governmental restriction of choice.

Link: http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20051025-16091900-bc-us-growthhormone.xml

Pro-Healthy Life Extension Investors Exist
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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.

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More On Centenarian Studies
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(From the New York Times). Centenarians and centenarian studies are popular topics in the media this month; one would hope that this indicates an increasing interest in the prospects for future healthy life extension. "From the approximately 50,000 centenarians counted in the 2000 census, demographers expect the number to soar; one census estimate is that there will be about 800,000 by the middle of the century. Whatever the number, Mr. Olshansky said, centenarians are going to seem less extraordinary as improvements in medicine and other factors make it easier to live longer. 'Centenarians today had to survive an incredible array of environmental insults and infections that make them a much more highly selected group of individuals than we're going to see in the future.'"

Link: http://www.nytimes.com/2005/10/30/weekinreview/30fountain.html

Near Future Medicine
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Here is a compact look at the near future of medicine from newindpress: "By 2010, both nanotechnology and stem cell research will have advanced to a point where they become integral, rather than radical, aspects of medicine and healing. ... But the really gigantic strides will come, most probably, from the world of stem cell research. These little prototype cells - which have not fully developed and taken on the characteristics of specific cells - can be manipulated to form any type of tissue - blood vessels, heart tissue, bone marrow, organs, you name it." I think that this neatly captures the appearance of progress in medicine - hot new fields become just another tool in the toolkit, and what was once amazing and unheard of becomes commonplace and relied upon.

Link: http://www.newindpress.com/sunday/sundayitems.asp?id=SEK20051029062924&eTitle=Health&rLink=0

SIRT1 and Human Longevity
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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.

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Is Life Good?
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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."

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More On Cell Therapy By Cytokine
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Randall Parker of FuturePundit has comments on the recent Italian demonstration of regenerative medicine by biochemical messaging: "Mind you, this is a news report on only 8 patients and not a journal article with a larger number of patients with controls and a detailed comparison of outcomes. Still, the approach is at least plausible. ... The technique might work less well in the really old because stem cell reservoirs in older people are aged and do not divide as quickly. However, one study found that elements in the blood of the old mice caused their stem cells to grow less rapidly. So it isn't so much that the stem cells are old but that they are getting signals telling them not to grow. Perhaps cytokines or other compounds can override those suppressor signals. So Marra's approach might work even for old folks."

Link: http://www.futurepundit.com/archives/003078.html

Alzheimer's: Fixated On Drugs
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(From MyDNA). The latest research news has a cancer drug demonstrated as beneficial for Alzheimer's sufferers. In "studies of mice that are genetically altered to be vulnerable to a disease that mimics Alzheimer's, the medicine increased the production of enzymes that break down beta-amyloid, a protein that accumulates and destroys cells in the brains of humans with Alzheimer's. In these studies, 80 percent of unmedicated mice were dead within five months; after five months, 80 percent of the medicated mice were still alive." This isn't as interesting as it sounds - it's by no means clear that this will help people - yet it received more press interest than progress towards viable immunotherapies that could actually cure the disease. Drugs are not the path to the future of medicine - they are a 20th century tool.

Link: http://www.mydna.com/health/mental/news/resources/news/200510/news_20051025_candalz.html

Novel Stem Cell Therapy
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From ANSA.it, news of a novel approach to stem cell based regenerative medicine: rather than extracting, culturing and reinjecting stem cells for autologous therapies, instead simply use appropriate biochemical signals that make the patient's body and stem cells themselves do all the hard work. "In the new technique, hormones called cytochines are injected into the body during the 24 hours after emergency heart surgery and immediately spur the production of stem cells in spinal fluid. The stem cells race to rescue the damaged heart ... The acute inflammation of the heart attracts the stem cells whose role in the body is to repair cardiac tissue ... Tests on eight patients who were operated on immediately after a heart attack have produced 'amazing' results."

Link: http://ansa.it/main/notizie/awnplus/english/news/2005-10-27_1806160.html

More Dr. Weil and the Lie Down and Die School of Thought
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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.

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Chasing Biomarkers Of Aging
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Practical biomarkers of aging are an important agenda item for most gerontologists: how do you tell whether a potential anti-aging therapy works without waiting years and counting deaths? Some would debate that you can even validate a potential biomarker without waiting years and counting deaths - which is a problem for those of us who would like to tackle the problem of aging on a shorter timeframe. Fortunately, it seems likely that you can't go far wrong by simply addressing as much cellular damage as you can - just as we go about repairing or maintaining any complex system. This Newswise release discusses a slightly different sort of biomarker of aging; one useful for establishing actual age. This is beneficial for a wide range of animal studies - and potentially for validating the ages of human centenarians.

Link: http://www.newswise.com/articles/view/515666/

Greater Understanding, Metabolic Tinkering
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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.

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More Promising Stem Cell Medicine
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Via EurekAlert: "Left ventricular function and exercise capacity increased, while the area of heart muscle damage shrank, in 18 patients given infusions of their own bone marrow stem cells up to eight years after a heart attack ... The main results were at least threefold: an improvement in global left ventricular function by 15 percent, infarction wall movement velocity rose 57 percent, and there was a significant reduction of infarct size by 30 percent. Concerning all those parameters, no significant changes were seen in a representative control group ... The stem cell therapy demonstrates that restoration is possible, clinically feasible and associated with an improvement of the performance of the heart by approximately 20 to 30 percent. This therapy is safe, similar to an 'own blood injection or transfusion,' and has no side effects."

Link: http://www.eurekalert.org/pub_releases/2005-10/acoc-bms102605.php

NanoBioEthics
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Ronald Bailey makes sensible points on the immorality and waste of bioethics at Reason Online: "Nanotech integrated into the very cells of our bodies will dramatically lengthen our life spans, give us superhuman mental capacities, and enable to us manipulate literally every aspect of the material world including the material that makes us. ... Waiting until the ethicists catch up with scientific and technological progress is a recipe for technological stagnation. Slowing innovation is not cost free. It makes a difference to tens of millions of people whether a cure for cancer or heart disease is found in 2010 or 2020." Or whether healthy life extension research and real, working anti-aging technologies prosper.

Link: http://www.reason.com/rb/rb102605.shtml

Truth In Satire
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The satirists at the Spoof craft a better class of article on attitudes towards longevity and healthy life extension research. Best read out loud in a Groucho Marx voice: "People are sick of dieing. They feel that things will be too uncomfortable without existence. People would rather live to be 100 or older, even if it means having to buy a whole new wardrobe. ... In a poll taken recently, most Americans said they don't want to live to be so old that they cannot wash their armpits without help. If researchers could make it possible to live to 120, other Americans said they would accept that. However, most worry that they'll become unable to use a bow and arrow or have problems running. 'Old age isn't so bad if you can still run at a decent speed.'" For a more serious look at poor attitudes towards longevity based on misconceptions about health, turn to the Fight Aging! blog.

Link: http://www.thespoof.com/news/spoof.cfm?headline=s5i9581

On The A4M Lawsuit
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The Scientist gets up to speed on the lawsuit filed by the American Academy of Anti-Aging Medicine (A4M) against aging researchers Olshansky and Pearls. "Daniel Perry, executive director of the Alliance for Aging Research, a Washington, DC-based non-profit that seeks increased funding for aging research, said he does not hold much stock in A4M's findings, and hopes the lawsuit doesn't give the organization more attention than it deserves. "Since we want to have the public understand aging better, and how to age with health and vitality, we want them to be getting their information from credible sources. To create an equal standing for some who are at least as interested in moving products as they are in providing unbiased evidence-based information to people is counterproductive.'" You'll find more on the roots of this dispute here at the Longevity Meme.

Link: http://www.the-scientist.com/news/20051025/02

$20,000 SENS Challenge Update
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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.

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USA Today On Calorie Restriction
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Mainstream reporting on calorie restriction and longevity has improved greatly over the past few years - the results of education and advocacy in action. We can hope that a similar trend will show in reporting on the future of radical life extension and the development of real anti-aging therapies capable of preventing and reversing cellular damage. From this USA Today piece: "'It is the only nutritional regimen thought to retard aging,' says Richard Weindruch at the University of Wisconsin-Madison. His studies have suggested that middle-aged mice can start the diet and still get the longevity benefit. ... In an ongoing study of monkeys, Weindruch has found that the very low-calorie diet seems to shield these animals from type 2 diabetes, a common disease of old age."

Link: http://www.usatoday.com/news/health/2005-10-23-bare-minimum-diet_x.htm

A Profile Of Aubrey de Grey
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The Chronicle of Higher Education profiles biomedical gerontologist Aubrey de Grey, originator of the SENS proposals for producing actual, working anti-aging medicine: "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. ... One hundred and fifty thousand people die every day, and two-thirds of those die of aging in one way or the other. If I speed up the cure for aging by one day, then I've saved 100,000 people."

Link: http://chronicle.com/free/v52/i10/10a01401.htm

Quotable Quotes and a Live, Online Discussion With Aubrey de Grey
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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.

...

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!

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Centenarian Envy
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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.

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Klotho And Calcium Regulation
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Forbes reports on the results of futher study of the klotho gene; you may recall the work linking klotho and aging, as well as some doubts as to whether anything significant had in fact been demonstrated. From the article: "Using a heretofore unknown mechanism, klotho, which is found in cerebrospinal fluid, urine and blood, helps to control blood calcium concentrations by regulating the amount of calcium that is allowed to enter cells ... Previous studies showed that aging is associated with calcium imbalances. ... As we age, it is more difficult to absorb calcium. So this might be due to the fact that these people have less klotho. The finding of the activation of the calcium channel by klotho may form the link between the negative calcium balance observed in the elderly."

Link: http://www.forbes.com/lifestyle/health/feeds/hscout/2005/10/20/hscout528622.html

More Bone Regeneration
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The development of regenerative medicine for bone is proceeding nicely. The Globe and Mail reports on another new technique: "Using a protein that can seduce adult stem cells into becoming bone tissue, Cameron Clokie, head of oral and maxillofacial surgery at the University of Toronto, has pioneered a technique to reset the jaw's skeletal clock - coaxing bones to grow as they do in a newborn baby. ... This is pretty much back to the embryonic state of bone generation. With this patient we've actually regrown a jawbone that is identical [to the one] he lost. ... research has shown [bone morphogenetic protein] can affect the stem cells known to circulate in the body, even in adulthood."

Link: http://www.theglobeandmail.com/servlet/story/RTGAM.20051022.wxchin1022/BNStory/specialScienceandHealth/

More On Centenarians
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From WFMY News, an overview of present knowledge regarding what contributes to present day human longevity. "Genetics clearly were critical to their long lives. It might skip a generation, but clearly the genetic component was in each of them. ... Each had siblings, parents, or grandparents who had lived a century, or nearly so. ... Each was born to rural life where hard physical work was the constant. It provided a healthy diet, fresh vegetables, fish, soy, and grains, although none was ever a big eater." The article goes into more detail, but the translation to general recommendations likely to increase your healthy life span is all common sense. In many ways, this is somewhat academic - your life span depends far more on the speed with which real anti-aging medicine is developed and commercialized. So support this research!


Link: http://www.wfmynews2.com/news/article.aspx?storyid=50647

Boost For Systems Biology
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The Seattle Post-Intelligencer notes new funding for the Institute for Systems Biology, an organization we've discussed previously. "The Institute for Systems Biology has received grants worth $13 million to recruit faculty and support research that could extend a person's life ... The Bill & Melinda Gates Foundation has issued a $10 million challenge grant of which ISB has already received $2 million. Amgen, the biotechnology company, has contributed $3 million. ... To receive the remaining money from the Gates Foundation, ISB will need to raise additional funds. Hood envisions a new type of medicine, which is based on DNA mapping, blood analysis, technology and prevention that could extend a person's life by 10 to 20 years."

Link: http://seattlepi.nwsource.com/business/245227_isb20.html

Correlations in Retirement and Longevity
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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.

...

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?

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Better All The Time: Mprize Edition
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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!

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Down With The Miserabilists
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The Times makes a point I've been stressing for a while - the ridiculous nature of any attempt to paint increasing longevity as a problem: "Yet the 'ageing population' is seen as a big problem. It is assumed that more old people having a longer old age equals more people in expensive misery, needing ever more medical care. Why is there such a 'miserabilist' response to the increases we've seen in life expectancy in rich countries? The evidence is that the levels of ill-health and disability in older people at any given age are falling - a tribute to the effectiveness of health promotion, preventive medicine and acute medical care. Old people are living not only longer but also in better nick. ... If this means that we have to work longer, so be it. After all, you get weekends and evenings off at work. Death offers no such perks."

Link: http://www.timesonline.co.uk/article/0,,8123-1835226,00.html

National Geographic On Longevity
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The National Geographic looks at the prospects for enhancing human longevity through science in this article. The contents are mainstream and nothing new, but it's good to see the concepts of healthy life extension spreading in a somewhat more positive context than was prevalent a few years ago: "When asked about the most plausible methods for prolonging human life, Rose said, 'First drugs and then organs cultured using stem cells from your own tissues. It's just like cars are better now than they were at the turn of the century. We'll be able to give you a new body, bit by bit, and pathway by pathway. I don't necessarily think anyone should feel they need to live longer, nor do I see life extension as a moral virtue or a societal goal. But I am saying that if it's something you want to do, then we can offer the technical possibilities.'"

Link: http://news.nationalgeographic.com/news/2005/10/1020_051020_human_lifespan.html

Regenerative Medicine Is But a Part of the Story
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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.

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On Korean Research Plans
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Impressive South Korean progress in stem cell research - using a fraction of the resources employed in other regions of the world - demonstrates what can be achieved in an atmosphere of public support and enthusiasm for medical research. From the Digital Chosunilbo: "We are one step ahead: there is no need to get big-headed. For cell cloning technology to be used in clinical treatment, we need the technology to grow stem cells into particular organ tissues, and there we lag behind the U.S. and Britain ... Stem cell research can make a contribution to national wealth as well as national prestige only if it can be used in the clinical treatment of patients suffering from as-yet incurable diseases. And for that we need a safe, cheap and effective treatments using stem cells, and systematic cooperation with experts in veterinary medicine, immunology and molecular biology and other related fields."

Link: http://english.chosun.com/w21data/html/news/200510/200510200031.html

Regeneration From Fat Stem Cells
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Via Hype and Hope, news of further progress towards regenerative therapies based on the use of adult stem cells from fat (adipose tissue): "This is the first preclinical study in which the injected cells were autologous, meaning they came from the animals' own tissue, were not cultured, so that they did not undergo multiple cell divisions to achieve a target dose of cells, and were harvested and administered on the day of the heart attack. ... Additionally, it shows that a sufficient number of cells could be accessed from adipose tissue in real-time to achieve a therapeutic effect, which closely approximates a clinical setting where timely delivery may be critical." The absence of extra steps, such as culturing, would seem likely to lead to a comparatively low-cost procedure once commercialized.

Link: http://www.hypeandhope.com/wt/page/index/it_1129748357

Stem Cell Capabilities Growing
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(Via ScienceDaily). Dramatic dvances in the field of medical research are built upon improvements in very ordinary, everyday underlying technologies and capabilities. You have to watch the infrastructure to understand the big picture: "A team of bioengineers led by the University of Toronto has discovered a way to increase the yield of stem cells from umbilical cord blood, to an extent which could broaden therapeutic use of these cells ... From their studies in mice, the researchers know that new stem cells obtained through their expansion technology can engraft in bone marrow and maintain special properties such as the ability to migrate in the body." The researchers are optimistic on moving ahead to use these cells in clinical trials in 2006.

Link: http://www.sciencedaily.com/releases/2005/10/051018072309.htm

Foresight Nanotechnology Conference Starts This Weekend
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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.

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Measuring the Effects
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The Daily Princetonian reports on a study measuring the effects of years of anti-research politics in the US: "The United States' share of new publications in stem cell research is unexpectedly low and declining, according to a recent paper by Aaron Levine, a doctoral candidate in the Wilson School. The paper speculates that the U.S. political environment may be a factor. ... The United States' share of embryonic stem cell publications was 30 percent, compared to an average of 51 percent for five other biomedical technologies including DNA microarrays, polymerase chain reaction, yeast two-hybrid screening, green fluorescent protein expression tagging and RNA interference."

Link: http://www.dailyprincetonian.com/archives/2005/09/26/news/13201.shtml

Yet Another Potential Cancer Therapy
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Barring poor luck, it seems unlikely that I will die from cancer. I may be greatly inconvenienced by cancer, financially at the very least, but not killed. I take the same view of Alzheimer's - the scientists and researchers tackling these age-related conditions are well established, well funded and making progress. We may not be anywhere near as close as we'd like to a cure for cancer, but the institutions of cancer research are in place and ready to benefit from falling costs and increasing capacities in biotechnology. I feel confident that these diseases will indeed be reduced to the status of obscure threat or minor chronic condition within the next twenty years - the momentum is there. As an example of the sort of basic research that encourages optimism, here we have a recent advance in immunotherapies for cancer:

Research in Immunology and Cancer (IRIC) of the Universite de Montreal, has succeeded in developing a new approach to eradicate malignant melanoma tumours in mice. The findings of Dr. Perreault and his research team are reported in an article just published in the online edition of Nature Medicine, and soon to be published in the print edition of the publication.

In brief, the method developed by Perreault consists of administering T-lymphocytes - cells whose function it is to recognize and destroy abnormal cells - from a healthy mouse donor to mice with cancer. These lymphocytes are pre-immunized against a specific antigen (H7a) present in host mouse cancer cells. Although the target antigen is found in some of the host's healthy cells, the treatment does not cause any side effects because the anti-H7a lymphocytes cluster almost exclusively around the tumour site where they are attracted to the molecule VCAM-1 present on the blood vessels that irrigate the tumour. The T-lymphocytes produce interferon gamma and perforine/granzyme to eradicate cancerous cells.

"We are very pleased with the insights yielded to date from this research project which our team initiated in 2003, explains Dr. Perreault. Thanks to another five-year grant from the Canadian Cancer Society, we have moved on directly to explore the cancer-curing potential of this immunotherapeutic method in the treatment of human melanoma. We may be only a few years away from testing the application on human beings. The prospect of this work leading to the development of an effective, nontoxic and non-invasive therapy against certain types of cancer for broad clinical use is exciting for every basic research students, scientist and doctors working on this project."

Barely a month goes by without an equally promising advance from cancer researchers; this state of affairs is the end result of a long history of hard work by patient advocates, scientists and activists. It makes you wonder just what we would be seeing from biomedical gerontology in terms of progress towards working healthy life extension therapies if the field were funded and supported to the degree it deserves.

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More On Calorie Restriction
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The Life Extension Foundation News is reprinting an interesting article: "It is widely held that caloric restriction (CR) extends lifespan by preventing or reducing the age-related accumulation of irreversible molecular damage. In contrast, our results suggest that CR can act rapidly to begin life and health span extension, and that its rapid genomic effects are closely linked to its health effects. We found that CR begins to extend lifespan and reduce cancer as a cause of death within 8 weeks in older mice, apparently by reducing the rate of tumor growth. ... Further, in late adulthood, acute CR partially or completely reverses age-related alterations of liver, brain and heart proteins. CR also rapidly and reversibly mitigates biomarkers of aging in adult rhesus macaques and humans."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2843&Section=AGING

Living To 100 And Beyond
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From the Society of Actuaries: "Centenarians represent one of the fastest growing age groups in the U. S. Yet, factors indicating longevity and its time trends remain to be fully understood. Natalia Gavrilova and Leonid Gavrilov conducted this research, which explores possible predictors of exceptional human longevity such as familial factors, early-life living conditions, month-of-birth, and birth order." Actuarial data is of interest, if only to remind us that no existing influence on your potential healthy life span even begins to compare to the effects of future medical research and working anti-aging technologies - it's up to us to make sure those effects are large and positive!

Link: http://www.soa.org/ccm/content/areas-of-practice/life-insurance/research/search-for-predictors-of-exceptional-human-longevity-/

Scott B. and Anne P. Appleby Charitable Trust Donates to the Mprize
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It's always good to wake up to the news that my favored charitable cause has gained another respected donor organization. From Dave Gobel, news of another large lump sum for the Mprize for anti-aging research:

The Scott B. and Anne P. Appleby Charitable Trust has donated:
$20,000 for the Longevity Mprize
$20,000 for the Rejuvenation Mprize
$15,000 for [Methuselah Foundation] directed purposes including expenses for Aubrey de Grey

The Mprize fund is within $100,000 of the end of year goal of $2 million in pledges - only four more members of The Three Hundred and we'll be there. Congratulations to the Methuselah Foundation volunteers on the results of their hard work, and many thanks to the many donors who have stepped forward to make a committment to the future of healthy life extension medicine.

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Bioethics, Ignorance Versus Progress
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The Stanford Daily provides an excellent example of the way in which institutionalized bioethics has largely become an exercise in hindering research from a position of ignorance: "But at the moment, Weissman's proposed mouse project still has not begun as he waits for the scientific community's approval after reviewing the ethical concerns raised by the experiment. 'This project will test human neuronal cells in a mouse brain micro-environment as a prelude to studying stem cells that have human genetic diseases like Alzheimer's, Parkinson's, Lou Gehrig's, and cerebral palsy. Which of these diseases should we not be working on as fast as we can?'" A salaried bioethicist has no incentive to help people by speeding research - the incentives in this position are all in the direction of inventing new obstacles to progress in medicine.

Link: http://daily.stanford.edu/tempo?page=content&id=18153&repository=0001_article

The Business Of Regenerative Medicine
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From PharmaLive, a look at the business of regenerative medicine, which "offers the possibility of replacing damaged or diseased cells and tissues. If it were possible to replace insulin secreting cells in the pancreas, type I diabetes could be cured. If it were possible to replace dopamine-secreting cells in the brain, Parkinson's might be cured. Cures, not just palliative treatments, are promised by regenerative medicine. ... There are over 200 tissue types in the human body; the loss or degeneration of any individual type is likely to cause disease or at least unwelcome changes in appearance. ... the worldwide revenues for cell and cytokine therapies in regenerative medicine is estimated at $12.7 billion in 2005. This market is expected to expand to $20.7 billion in 2010, an AAGR (average annual growth rate) of 10.3%." The potential for business success drives private research funding in any field.

Link: http://www.pharmalive.com/News/index.cfm?articleid=281328&categoryid=15

The Latest From ACT
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(Via Genetic Engineering News). Advanced Cell Technology (ACT), now funded again, is refining the technology and capabilities of stem cell research. Most of the press has focused on entirely the wrong part of this research: "We have shown in a mouse model that you can generate embryonic stem cells using a method that does not interfere with the developmental potential of the embryo." The more important story here is the advances in basic technology and degree of control that enable this sort of work: "In the past, stem cell lines have been isolated from the inner cell mass of blastocysts and in a few instances, from earlier, cleavage-stage embryos. We generated five [embryonic] and seven trophoblast stem (TS) cell lines from single mouse embryo cells. The stem cells were able to generate all the cell types of body, including nerve cells, bone, and beating heart." This year ACT, next year all the leading research groups.

Link: http://www.genengnews.com/news/bnitem.aspx?name=1080009XSL_NEWSML_TO_NEWSML_WEB.xml

Not Just Better, But Faster Too
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The BBC reports on a clever direction of research in tissue engineering: "UK scientists say they can cut the time it takes to grow new tissue from days to minutes. ... The next stage is to test whether this method could help repair injured tissues. Ultimately, the goal is to design a rapid, inexpensive, automatic process for creating strong tissues which could supply hospital surgical units with a tool kit of spare parts for reconstructive surgery. The speed and control it offers means that our method could one day be used to produce implant tissue at the bedside or in the operating theatre." It's only a first demonstration on one specific tissue type, but it's still impressive.

Link: http://news.bbc.co.uk/1/hi/health/4342204.stm

Closer, But Still Missing The Point
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An op-ed in the Australian has fun with the imagined nuts and bolts of a 1000-year life span and actuarial escape velocity - the result of advancing medical technology. "I think I last gave you an update on my busy life two years ago, on the occasion of my 300th birthday. At that stage, the human lifespan was understood to be an all-too-brief 500 years or so. But now that new advances in gerontology have stretched our fleeting time on this earth to a full millennium, I feel all sorts of new possibilities - and difficulties - opening before me." The missed point? That the long-lived character is alive and healthy rather than suffering the alternative - and that even an op-ed columnist can plausibly imagine enjoying a full and rewarding life for hundreds of years. Boredom is an entirely elective activity, no matter how long your life.

Link: http://www.theaustralian.news.com.au/common/story_page/0,5744,16937398%255E37556,00.html

First Bricks Laid for the Simulated Mouse
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I'm not made happy by the necessity of animal research in medicine; we all have a little of the paradise engineer in us. In my case, I think that we have something of an obligation to work towards extending relief from suffering to those beings not as intelligent as ourselves. But animal research is necessary, very much so if we are to move as rapidly as possible into an era of radically extended healthy life spans. This will continue to be true until we can adequately simulate almost all of what we need to find out - a point I've made before:

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.

Financially attractive experiments using simulated animal (or human) tissue or bodies don't just require stable software platforms and falling costs of processor power; they also require a large foundation of research and data. You have to make sure that your simulation reflects reality through a suitable (and invariably painstaking) program of analysis of and checking against reality. One of the first steps on this road - albeit a largely inadvertent step, made with different and more immediate goals in mind - is underway in Europe:

In Venice this weekend, scientists launched a €100 million EU programme to breed millions of genetically engineered mice. The aim is to recreate all the main human ailments - diabetes, heart disease, cancer and mental illness - in the mouse. In doing so, the genetic and environmental roots of these conditions will be exposed and new paths to the creation of drugs and treatments revealed.

...

The EuroMouse programme will involve using a strain of mouse known as the BL/6 or Black Six. These are already used extensively in laboratory experiments and are completely inbred. Each male is an exact clone of all other Black Six males, and similarly for females, no matter if used in an Australian or an Austrian laboratory.

From their populations of Black Sixes, EuroMouse scientists will take embryos, delete or modify one of the genes in them, and then put the genetically engineered embryos back into mice wombs to create a new population, one that has a single mutant gene inside each member.

This process will then be repeated for each of the mouse's 20,000 genes. 'Eventually, this will give us 20,000 strains of mice, each with a different mutated gene,' added Birney.

Each mouse strain will then be observed to see how this mutation manifests itself in the animal's appearance and behaviour. Thus, scientists will find out what each mouse gene does and, from that, what each corresponding human gene does.

This type of project has already been accomplished for yeast; these breeding projects and the resulting analysis is an important part of the groundwork for the future of much more efficient, rapid and effective simulated experiments in medical research.

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The Line Between Health Advocacy and Aging Apologism
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My eye was caught - hard to avoid noticing if you spend any time perusing health websites - by Dr. Weil's latest round of combined business advertising and health advocacy. The good doctor is an excellent example of the sort of health advocacy that also serves as an apologism for degenerative aging. The latest Time cover story is a good example of the sort of commentary I have in mind. "Degenerative aging - what a thing! It's just great to slowly lose your faculties, capabilities, and ultimately your life, if you only go about it this way." I exaggerate, but the real thing isn't much better. Whatever we might like to tell ourselves, age-related degeneration is not good, never good:

Without action now, your future will be one of pain and suffering, of the slow destruction of your body and mind. Aging is not noble. It is not romantic. It is a slow and increasingly terrible disease - no one goes quietly or with dignity.

I realize that it is simply human nature to justify to yourself the general excellence and correct nature of the slowly heating pot of water you happen to find yourself in - it seems to be a helpful adaptation when you can do nothing about the situation. But the years in which "nothing can be done" was true for aging are now past and gone; it is quite clear that patient advocacy for directed, serious anti-aging research could have startlingly effective results over the next 20 to 30 years.

Keep this in mind the next time you read commentary from a health advocate. They may be talking good sense on general health matters, but at the same time most tend to romanticize, accepting and excusing the ugly realities of aging. That's not a good message.

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Alcor's "Limitless Future"
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Folks at the Immortality Institute have recommended the Alcor Life Extension Foundation's latest outreach book and video. Alcor, the largest cryonics provider, has become more focused on publicity in the past two years; my view is that this is a very necessary part of growing the cryonics industry beyond the niche it currently occupies. If the potential for cryonics to save millions of lives over the next few decades - lives that will be lost waiting for working anti-aging medicine to be developed, no matter how fast the research community can make that happen - is to be realized, then meaningful organizational and industry growth must get underway as soon as possible.

Link: http://www.alcor.org/cgi-sys/cgiwrap/alcor/public/InfoRequest.cgi

Aubrey de Grey On Gompertz Slopes
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Something a little more mathematical and abstract today; via the Gerontology Research Group and transhumantech mailing lists, here are some interesting comments on the relevance to aging of the slope of the Gompertz curve:

In keeping with my prevailing status as angry young man of gerontology I think it is time I commented on the use of the Gompertz slope as a measure of the rate of aging. Let's be quite clear, this idea rests on a generalisation that is broadly true across natural species (ones that have not been manipulated by biotechnology to live longer) but that we have absolutely no reason to believe will be true for ones that have been thus manipulated, and in particular for humans that are receiving future medical care. This generalisation is that the mortality rate doubling time (which is just ln(2) over the Gompertz slope) is pretty accurately a constant multiple (across species) of the life expectancy -- around 1/10 of it. In other words, survival curves for different species are rather well superimposable just by altering the scale on the x-axis. (This is the same statement because the maximum slope of the survival curve is essentially a constant multiple of the Gompertz slope in populations exhibiting a negligible Makeham term, and we are generally considering such populations if we look at vertebrates in captivity with state-of-the-art husbandry, or at humans in the West.) It is therefore of very little scientific (let alone biomedical) value to say that when an intervention lowers the Gompertz intercept but not the slope that it has not slowed aging: one could just as well say that it has indeed slowed aging but has also lowered the variability of the rate of aging within the population. The example I used in my latest editorial in Rejuvenation Research is that if you take two populations with somewhat different Gompertz intercepts and identical Gompertz slopes, and you then compute the Gompertz parameters of the population made by combining these two populations into one, it will have a lower slope (a longer mortality rate doubling time) than the component ones do. If that doesn't make a mockery of using the slope as a measure of the rate of aging, I don't know what would.

You'll find a little more exposition on the use of Gompertz slopes in the middle of a recent post at Longevity First. As for most topics in gerontology, discussions on the validity of Gompetz slopes as a measure of aging have extended over many years. Here is the abstract for a paper from 2001, for example:

The Gompertz transform of the distribution function for the age at death expresses mortality in a form R = R_0e^[alpha] t where R_0 is the mortality at time zero and [alpha] is the rate of increase of mortality, frequently taken as the rate of ageing. The slope of the line [alpha] is frequently used as a measure of the rate of ageing. It is argued that it is incorrect to use [alpha] in this way. To support this contention, a paradox is produced whereby selection for longevity increases [alpha], which could lead to the absurd conclusion that selection for longevity increases the rate of ageing.

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Transcending Red Tape
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Sonia Arrison's latest article from TechNewsWorld restates this week's unofficial Longevity Meme theme: present overregulation harms our prospects for future health and longevity. "Right now in the United States, we have a five-to-ten-year delay on new health technologies for FDA approval (with comparable delays in other nations). The harm caused by holding up potential lifesaving treatments (for example, one million lives lost in the United States for each year we delay treatments for heart disease) is given very little weight against the possible risks of new therapies ... The FDA has done enormous harm to the health of the American public by greatly increasing the costs of pharmaceutical research, thereby reducing the supply of new and effective drugs, and by delaying the approval of such drugs as survive the tortuous FDA process."

Link: http://www.technewsworld.com/story/46713.html

Calorie Restriction, Metformin
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ScienCentral outlines some of the current scientific thinking on calorie restriction (CR) and drugs that might mimic its beneficial effects on health and life span: "The most common drug used in managing Type 2 diabetes, generically known as Metformin, was a standout - it sparked a very similar pattern to calorie-restriction. ... Metformin did a wonderful job of reproducing those effects. It looks almost exactly like calorie restriction in its effects. And so we're hopeful that that one drug might have similar effects on lifespan and on health. ... Unfortunately we don't really know yet whether that will mean that metformin will extend the lifespan of healthy animals or healthy people." The future of healthy life extension is not calorie restriction - but CR the best option available today for people who want to remain healthier for longer.

Link: http://www.sciencentral.com/articles/view.php3?type=article&article_id=218392663

A Strong Sign Of Brokenness
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When affluence causes problems, it's a strong sign that the system is broken. Such is the case in wealth transfer schemes such as social security in the US or pensions in Europe; the affluence in question is the increasing length of healthy, productive life span. What a mess has been fashioned whereby longevity begats problems!

Belgium was shut down Oct. 7 by a general strike. Unions didn't want the retirement age lifted from 58 to 60. Yet Belgium, like many rich nations, has little choice. People are living longer and too many will soon be drawing benefits. In Britain, too, unions threaten a national work stoppage over a plan to raise the retirement age for public-sector workers to 65 from 60.

In America, poll-conscious politicians haven't raised the age for receiving full Social Security in a couple decades. (For workers born in 1960 and later, the age will rise from 65.5 by about two months a year until it reaches 67 in 2027.) Yet the first baby boomers hit 60 this year, and that generation - 78 million strong - can't possibly have their pension and medical costs subsidized by fewer, younger workers.

The culture of entitlement combines with the leverage provided by ever-growing government to make problems where none should exist. Humans are selfish, jealous creatures, but competition, rule of law, strong property rights and the requirements of responsibility can make virtues of these urges, harnessing them in service of progress. Sadly, there's all too little of that going on these days - it's a battle in many countries simply to gain the liberty from repressive laws to work as you would like in later life.

The institutions of retirement must change, indeed will change as medical technology adds ever more healthy years. The key to removing the entirely artificial "problems" of increasing human longevity is very simple: freedom. Freedom to work if healthy, freedom to voluntarily provide for the frail either directly or by supporting medical research, and freedom from forced wealth transfer to those older, and on average wealthier, than yourself.

These are things to bear in mind when planning for your long term future. It's not just health and savings - it's ensuring that medical progress and prosperity will continue in the face of what most modern nations are becoming.

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Calorie Restriction, Nitric Oxide
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WebMD takes a look at a recent study on the biochemistry of calorie restriction: "The results showed that mice that were fed 30% to 40% fewer calories produced more nitric oxide than those who followed an unrestricted diet. Calorie restriction also caused the mice to increase production of another chemical messenger that stimulated production of new mitochondria (the main energy source in cells) and increased oxygen consumption and expression of a protein previously shown to play a role in calorie restriction's effect on life span. These beneficial effects of calorie restriction were not found in mice that lacked the enzyme necessary to synthesize nitric oxide. Therefore, researchers say the findings suggest that nitric oxide may play a critical role in calorie restriction's effect on longevity."

Link: http://my.webmd.com/content/Article/113/110801.htm

Surveys, Surveys
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For those who like to follow such things, EurekAlert reports on a recent survey of support for embryonic stem cell research in the US: "The survey found wide support for embryonic stem cell (ESC) research that cut across political, religious and socio-economic lines, with two-thirds of respondents either approving or strongly approving of human embryonic stem cell research. Even Fundamentalist and Evangelical Christians – long considered to be the most hard-line opponents of embryonic stem cell studies -- split evenly on approval for embryonic stem cell research." We can hope that anti-research groups have done their worst: scientific and medical progress already suffers from the consequences of overregulation, never mind the efforts of those who would turn back the clock and have us all suffer and die needlessly.

Link: http://www.eurekalert.org/pub_releases/2005-10/gpp-crn101305.php

Trials in the UK, In Business in Thailand
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It is interesting to note that the medical research community in highly regulated countries - the UK in this case - is still in the process of trialing adult stem cell therapies for heart damage:

The first part of the study will involve 300 patients whose hearts are failing because of heart disease or a previous heart attack.

A second arm will involve 200 patients whose hearts are failing specifically because of dilated cardiomyopathy - a heart muscle disorder.

And a final element will involve 200 patients who have just had a heart attack.

Some patients will have stem cells extracted from bone marrow in their hip and injected into their major coronary arteries or directly into their heart.

Others will receive injections of growth factor drugs to try to cause stem cells to spill out of their bone marrow and into their blood without the need for the operation.

You might recall that even trials of this sort of work were blocked in the US by the FDA until successful tests were conducted in South America. Meanwhile, today, the same class of stem cell treatment for heart disease discussed above is commercially, responsibly available to the paying public in Thailand.

Centralized, unaccountable, state regulation of medicine and medical research is simply incompatible with rapid, effective progress - it leads to greater levels of death and suffering than would otherwise be the case. Entities like the FDA and its overseas counterparts must be dismantled, and the process of accountability in medical research left to the free market in reviewing and rating concerns - i.e. those that will actually do a good, cost-effective job.

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UK Funding For Limb Regrowth
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The Guardian reports that a UK team has received further funding to explore salamander-like regeneration in humans: "British scientists have been awarded £10m to develop genetic treatments that could enable humans to regrow limbs damaged by accidents or surgery and allow patients to recover from wounds without scarring. The ambitious project aims to unravel the genetic quirks that allow certain amphibians, such as frogs and salamanders, to recover from severe injuries by regenerating fresh body tissues. ... Dr Amaya's team hopes to identify the genetic factors at work and develop drugs that would coerce the human body to heal itself when damaged ... the goal of regrowing limbs was not beyond human grasp. 'It's an achievable future, it will eventually happen.'"

Link: http://www.guardian.co.uk/uk_news/story/0,,1590008,00.html

The FDA Must Go
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Ronald Bailey takes a somewhat more polite and moderate tack on the FDA over at Reason Online. As do I, he thinks it must go or change greatly: "In the new era, patients who want to take advantage of the latest treatments will also have to agree to take more responsibility for the risks that come with using them. This century's biomedical revolution will sweep away the FDA's outmoded regulatory rituals; it's just a question of whether it will be sooner rather than later." The views at FDAReview.org or of other libertarians are also a helpful illumination of the damage that unaccountable FDA-style regulation does to medical progress and our prospects for future health and longevity. We don't have the luxury of time in the fight to defeat aging - those who block the path must get out of the way.

Link: http://www.reason.com/rb/rb101205.shtml

A Big Step Up For Gene Therapy: Permanence
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This news is most interesting:

"To date gene therapy has relied upon vectors that randomly insert genes into the cell's genome," explains Savio L. C. Woo, PhD, Professor and Chairman of Gene and Cell Medicine at Mount Sinai School of Medicine and corresponding author on the study. "The technique we developed identifies a specific sequence which only occurs in a few places in the mammalian genome. These sequences occur between genes so there is no danger of the insertion of the gene damaging existing genes in the cell.

"Because the genes are inserted permanently, a few applications would suffice to permanently correct a disease."

The key word here is "permanently." Genes inserted using existing methodologies don't stick around for long: gene therapy under those conditions is more analagous to courses of medication in that the patient's biochemistry is altered for a limited period of time only. Now, however, permanent correction is a possibility. That's a big step forward in the potential quality and effectiveness of gene therapy - it opens the door to comparatively low cost therapies for any condition that could be cured by adding a new gene or an additional working copy of an existing gene. We're one step closer to being able to reconfigure an adult human genome for therapeutic benefit - what interesting times we live in!

UPDATE: You'll find a discussion thread on this advance over at the Immortality Institute forum.

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The Future For CIRM
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The New York Times looks at what lies ahead for the California Institute for Regenerative Medicine: "In a nondescript temporary office across the bay from San Francisco, Zach W. Hall is about to lay the groundwork for the largest biomedical venture since the Human Genome Project. With $3 billion committed by the voters of California, his task is to shape the strategy that will best translate the promise of stem cells, which scientists hope will generate novel treatments for many intractable diseases." The article goes on to discuss the high level options, constraints and difficulties for scientific development in the years ahead; a good introduction for people new to the science beneath the debate.

Link: http://www.nytimes.com/2005/10/11/health/policy/11cali.html?pagewanted=print

Killing Cancer With Stem Cells
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ScienceBlog reports on a new usage of embryonic stem cells - employing them to construct immune cells capable of taking on cancer. "This is the first published research to show the ability to make cells from human embryonic stem cells that are able to treat and fight cancer, especially leukemias and lymphomas ... We hear a lot about the potential of stem cells to treat conditions such as Parkinson's disease, diabetes, and Alzheimer's disease. This research suggests it is possible that we could use human embryonic stem cells as a source for immune cells that could better target and destroy cancer cells and potentially treat infections." This is good science, and a good example of the sort of doors opened by increased knowledge of and control over cellular processes.

Link: http://www.scienceblog.com/cms/human_embryonic_stem_cells_used_to_kill_cancer_cells_9064

Mitochondrial Optimization and the Evolution of Human Longevity
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Humans live a long time compared to other mammals of a similar mass. Not long enough my tastes, but this distinction of longevity has spurred a great deal of scientific investigation and theorizing over the years. In recent work, Joao Pedro de Magalhaes suggests an association with evolutionary optimization of mitochondrial function:

A gradual optimization of mitochondria - the cells' powerhouses - may have occurred in the human lineage, which could be associated with the evolution of human longevity and intelligence.

...

Humans are not only the smartest primates but have the longest lifespan, and hence these results could indicate a gradual optimization of mitochondrial proteins in the lineage leading to humans as a means to delay certain forms of neurodegeneration. "It has long been argued that longevity and intelligence evolved together in the lineage leading to humans," says de Magalhaes. "In fact, some nonhuman primates develop neurodegenerative changes at considerably earlier ages than what is typically observed in human patients. Mitochondria have been associated with neurodegenerative diseases, including the genes whose human disease-causing allele was found to be the normal allele in some nonhuman primates, and the mitochondrial genome has been linked to aging. So the general pattern of these results could indicate a selection on the human mitochondrion associated with the higher human intelligence and extended lifespan. Still," de Magalhaes warns, "we will need more detailed studies to prove this hypothesis."

The evolutionary value of delaying the onset of neurodegenerative conditions would be much the same as that proposed in the grandmother hypothesis - capable elders increase the survival rate of their descendants.

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It Just Makes SENS
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A good op-ed from Kevin Perrott: "In regards to my interest in [the Strategies for Engineered Negligible Sensencence], I've always believed science would be able to address the fundamental challenge of aging. ... I realized that this could happen in mine, and perhaps my parents' lifetime as I tracked the developments in biotechnology. With this realization came the conviction to play a role in helping bring real anti-aging therapies to the clinic faster. Thus I became involved with the Methuselah Foundation and Executive Director of the Mprize, both efforts spearheaded by [biomedical gerontologist Aubrey] de Grey. I attended the SENS II conference because it is cutting edge and its focus, different from other aging conferences I've been to, is to highlight those technologies which can be used to actually do something about aging now, rather than just examine it."

Link: http://www.healthextension.net/archives/2005/10/it_just_makes_s_1.html

2006 CR Society Conference
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Registration has opened for the 4th Annual Calorie Restriction (CR) Society Conference in April 2006. The speakers list is still a work in progress, but researchers Aubrey de Grey, Steven Austad and Caleb Finch are already confirmed. The 2004 CR Society conference was a very worthwhile event for those interested in healthy life extension, and this should be just as good. "We are very excited about having our fourth conference in Tucson. Set aside the dates, meet fellow CR Society members in person, participate in an enjoyable, interesting, and educational conference. We are looking forward to meeting you." You can find out more about the CR Society - and the practice of calorie restriction - at the society website.

Link: http://www.calorierestriction.org/CR_Conference_2006.html

A Contrarian View
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From the Scientist, here is a contrarian view on the effects of restrictive US legislation on global progress in stem cell research. The author seems to be suggesting that change in the status quo of US government policies for medical research in this area spurred scientific groups to seek new opportunities for funding, more vigorous effects by pro-research groups to engineer other forms of public and private funding, and opportunistic development programs in other countries. I could craft a more libertarian version of this argument, but don't think it would hold together any better - the real damage to progress was not due to a lack of public funding for traditionally slow and unaccountable public research, but rather a result of threatened criminalization that scared away private funding from competitive, effective research.

Link: http://www.the-scientist.com/2005/10/10/12/1

Inflammation Gene Found
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EurekAlert reports that "a specific gene on chromosome 15 regulates inflammation, a finding with implications for a wide range of disorders, including cancer, cardiovascular disease, diabetes, obesity, Alzheimer's, and infections. ... this discovery will be of great interest to biomedical and pharmaceutical researchers because of an already heightened understanding of the role of inflammation in so many human disorders. ... [the gene is] a type of 'garbage truck' that helps clear cells of misfolded proteins that build up when cells are placed under stress, Blangero said. Inflammation develops when those faulty proteins accumulate in a cell. People with a genetic variation that impairs [the] ability to purify the cells by clearing out the bad proteins tend to suffer higher levels of inflammation."

Link: http://www.eurekalert.org/pub_releases/2005-10/mcow-sdi100405.php

Sixty-Six of The Three Hundred
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The sixty-sixth member of The Three Hundred signed up today, bringing the grand pledge total from these generous everyday philanthropists to $1.65 million - all in support of the realization of working anti-aging medicine, technologies capable of preventing and reversing the root causes of age-related degeneration. Because the Mprize is a research prize, these funds will be multiplied by the alchemy of competition and the human drive to succeed - the X Prize saw 16 dollars raised by competitors for every dollar in the prize, to pick one recent example.

Back when the Mprize volunteers were stalled chasing member number fifteen for Dave Gobel's clever fundraising concept, it was by no means clear that we'd be where we are now. But thanks to persistence, hard work and help from many quarters, here we are - sixty-six members to the Three Hundred and accepting six-figure donations to the Mprize fund. Onwards and upwards!

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Tissue Engineering With Fetal Stem Cells
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From Forbes: "Using cells from amniotic fluid, [researchers] were able to reconstruct defective tracheas (windpipes) in fetal lambs. ... This is one of several tissue-engineering methods developed at Children's Hospital Boston that uses the fetus's own cells - taken from the amniotic fluid that surrounds it - to create tissue to repair birth defects ... amniotic fluid, which is easily collected, contains unspecialized cells called mesenchymal stem cells. These stem cells can be used to make many of the tissues [needed to] repair a malformation while the baby is still in the womb or after birth - potentially even many years later." Based on this and other research, the storage of all these traditionally discarded materials sounds like a good plan. A pity it's too late for most of us - other methods must be developed for this sort of regenerative therapy in adults.

Link: http://www.forbes.com/lifestyle/health/feeds/hscout/2005/10/08/hscout528378.html

The Age On Aubrey de Grey, SENS
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The Age is running an article on biomedical gerontologist Aubrey de Grey and his Strategies for Engineered Negligible Senescence. As the article notes, advocacy for serious efforts to address the root causes of age-related degeneration is working: "De Grey's profile among biomedical researchers has gone from crank to useful crank to 'controversial theorist' over the past five years, with grudging admissions that some of his ideas may work. Last year, the US National Institute on Ageing - intrigued by de Grey's idea of using genes from soil microbes to clean up dangerous metabolic garbage that loiters in cells - subsidised a de Grey workshop. Yet the head of the institute continues to call some of de Grey's extrapolations 'silly'." We have a way to go yet, but the march towards high levels of funding and support for real anti-aging medicine continues - the sooner we get there, the more lives will be saved.

Link: http://www.theage.com.au/news/general/forever-young/2005/10/08/1128563036871.html

Sherwin Nuland on C-SPAN
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Via the Extropy-Chat list, John Grigg pointed out a C-SPAN interview with Sherwin Nuland:

I watched Dr. Sherwin Nuland (considered one of the three finest M.D. authors in the west) on C-Span and the subject of life extension came up in the interview. He felt "compressed morbidity" or the reduction & management of age-related breakdown until the very end of life was what we should be aiming for, and not life-extension (anything beyond 120 years in his view).

The reliability theory of aging suggests that any effort to compress morbidity will ultimately produce healthy life extension: all age-related degeneration is the consequence of acculumated cellular damage. Efforts to prevent and cure age-related disease will prevent or repair some of this damage, thus extending life span. Quite aside from this consideration, one has to look askance at this rather odd end goal: to aim at accomplishing an arbitrary healthy life span and then just let everyone die rather than continuing to explore the infinite possibilities offered by advancing medical science.

Nuland said he had recently spoken with Aubrey de Grey and went on about de Grey's plans for greatly extending lifespan (which he said were somewhat vague and not fully worked out yet) with a tone that was surprisingly almost friendly or at least neutral. The doctor calmly stated he disagreed with de Grey's goal of a human lifespan around 5-10,000 years. lol I wondered why de Grey had the arbitrary figure of 10,000 years as his finishing line. Why not 100,000 years?

This projected goal for human life span comes from a consideration of the fatal accident rate in a world in which death and disablility due to aging have been conquered. You'll find a further elaboration on this figure in Chris Lawson's The Tithonus Option is Not an Option. None of Aubrey de Grey's projections and goals are in any way arbitrary; you should take a look at his Strategies for Engineered Negligible Senescence website for much more information.

As with many doctors, Nuland wants to maximize life expectancy rather than expand lifespan. I did find it interesting that he said Leon Kass (who he claims to admire for his academic achievements) was too far right of the spectrum, while he himself was "just right."

You may recall that Nuland was the author of the rather obnoxious Technology Review article on Aubrey de Grey's work. He's in much the same boat as Leon Kass when it comes to healthy life extension technologies, but without the calls for government intervention to block their development and use.

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Understanding Nerve Regeneration
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From the Scientist, sounds of progress towards towards nerve regeneration: "Turning off a well-known chemical switch may allow severed nerves in adult mammals to regenerate, according to a report in this week's Science. By jamming the epidermal growth factor (EGF) receptor, the authors blocked harmful signals known to limit repair of damaged axons in the central nervous system. Their finding points to a promising new target for restoring neural function following injury. ... The beauty of this observation is that some drugs that will block this pathway have already been approved for the treatment of cancer. If further animal studies prove promising, the clinical work will move forward very quickly."

Link: http://www.the-scientist.com/news/20051007/01

Inability to Account For Change: Warnings Taken as Predictions
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From Zack Lynch's Brain Waves, a good example of the way in which conservative forecasts based on simple extrapolation of trends fail to account for the reality that is the future:

Twenty percent of us, according to a Rand Corporation study, are going to get cancer or another rapidly debilitating condition and we'll be dead within a year of getting the disease. Another 20 percent of us are going to suffer from some cardiac or respiratory failure. We'll suffer years of worsening symptoms, a few life-threatening episodes, and then eventually die.

But 40 percent of us will suffer from some form of dementia (most frequently Alzheimer's disease or a disabling stroke). Our gradual, unrelenting path toward death will take 8 or 10 or even 20 years, during which we will cease to become the person we were. We will linger on, in some new state, depending on the care of others.

To the end of this, we should mentally add "provided that nothing in medicine and research changes greatly." You should add that endpoint to most reports on the future of health and longevity (with a few enthusiastic exceptions). Excepts like the above are not predictions; rather, they are warnings, just as any serious consideration of your own personal future in the absence of advanced medicine should be a warning. This will be our fate unless we do something about it - and there is much that we can be doing! Folk like you and I can make a great deal of difference by advocating, supporting and encouraging medical research into cures for age-related disease and strategies to prevent the root causes of degenerative aging.

The future is what we make of it - and that is just as true for medical progress, health and longevity as for anything else.

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Tuning p53 Performance
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More interesting research into the p53 gene is ongoing; Medical News Today reports that scientists can now control its performance level. We know that the mechanisms associated with p53 suppress cancer by destroying cells with damaged DNA, but it may also be the case that upgrading its level of performance could cause accelerated aging - rather than extending life by giving us greater resistance to the detrimental effects of accumulated damage to nuclear DNA. We are entering an exciting era in biotechnology; the black box of the cell is opening up to inspection, manipulation and experimentation. Understanding a machine implies the ability to control, repair and improve that machine - and certainly the ability to extend its operational life span.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=31684

Reminder: Imminst Conference
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Via KurzweilAI.net, a reminder that the Immortality Institute conference is coming up soon: "'Enhance and Protect the Brain for Life Extension' is the theme of the Immortality Institute's Life Extension Conference scheduled for Nov. 5 in Atlanta. Speakers including leading gerontologist Aubrey de Grey, developer of SENS (Strategies for Engineered Negligible Senescence), will discuss anti-aging, cryonics, brain-computer interfacing, [general artificial intelligence], suspended animation, the legal rights of conscious computers, and biological immortality." There's still time to register; have a look at the list of speakers for a better idea of the flavor of the event, and drop by the Immortality Institute forums if you have questions.

Link: http://www.kurzweilai.net/news/frame.html?main=/news/news_single.html?id%3D4908

Stem Cells Repair Liver Damage
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Life Style Extra reports on more progress in regenerative medicine: "British scientists have successfully repaired patients' damaged livers by using bone marrow stem cells from their own blood. The [patient] is first injected with a drug which stimulates their bone marrow to produce extra stem cells. The stem cells are then harvested from the blood and injected into a vein or artery leading directly to the liver. Although the researchers are unsure what the cells then do they seem to help repair any liver damage." As for many adult stem cell therapies, it is still an open question as to the mechanism by which stem cells regenerate damaged tissue.

Link: http://www.lse.co.uk/ShowStory.asp?story=LJ518312D&news_headline=stem_cell_breakthrough_to_treat_liver_damage

Two Interesting Stem Cell Research Articles
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Two reports on new stem cell research caught my eye today. Neither promises immediate leaps forward in regenerative medicine this week or next, but both should be of interest to those who follow the underlying science.

Neural Stem Cells Are Long-lived:

New studies in mice have shown that immature stem cells that proliferate to form brain tissues can function for at least a year - most of the life span of a mouse - and give rise to multiple types of neural cells, not just neurons. The discovery may bode well for the use of these neural stem cells to regenerate brain tissue lost to injury or disease.

...

In terms of using neural stem cells for therapeutic purposes and to regenerate tissue, it's important that they can continue to proliferate, and that these stem cells can make different cell types. ... If these stem cells do produce cells that contribute to injury repair, it is fairly easy to infuse growth factors to coax these stem cells to do more in repairing injury.

Researchers have been making real progress of late in identifying, manipulating and culturing neural stem cells. Robust brain regeneration is high on my personal laundry list of things I'd like to be solved well before I'll have need of it - we can envisage many ways of dealing with a failing heart, up to and including cloning and transplanting a replacement organ or building mechanical substitutes, but the options for the aging brain are much more limited.

Stem Cell Subtype Aids Lung Patients:

High levels of a stem cell subtype called endothelial progenitor cells (EPCs) in the blood may improve the survival rate of people with acute lung injury, a deadly form of lung failure.

A study of 45 patients with acute lung injury by researchers at Grady Memorial Hospital in Atlanta found that patients with higher levels of EPCs had better survival rates. Patients with an EPC colony count of 35 or more had a death rate of 30 percent, compared with 61 percent for patients with an EPC colony count of less than 35.

That's a pretty impressive demonstration of the degree to which your survival depends on the effectiveness of your stem cells. Different people have more or less effective personal regenerative toolkits, but all those toolkits become steadily less effective with advancing age and accumulated cellular damage. How much of a difference will it make to the onset of age-related conditions when medical science can rejuvenate your stem cells?

Freitas, Merkle, Kinematic Self-Replicating Machines
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This post is a slight diversion from the normal topics of interest here, but not by too far. You may be familiar with the work of Robert Freitas on the future of nanomedicine, and you may have read his essay "Death is an Outrage" at the Longevity Meme. Robert Freitas and Ralph Merkle's latest collaboration - like the Nanomedicine volumes, part of the groundwork for the future of nanotechnology - is now available for free online:

With 200+ illustrations and 3200+ literature references, [Kinematic Self-Replicating Machines (KSRM)] describes all proposed and experimentally realized self-replicating systems that were publicly known as of 2004, ranging from nanoscale to macroscale systems. The book extensively describes the historical development of the field. It presents for the first time a detailed 137-dimensional map of the entire kinematic replicator design space to assist future engineering efforts.

To be able to build nanomedical machines capable of acting as blood cells or repairing damaged DNA, then we have to know - in detail - how to build nanomachines, period. So if you want an idea as to what the future of advanced nanotechnology in medicine will hold, and how fast it's coming along, you have to keep your eye on the dry nanotechnology field. Each new advance will be incorporated into medical devices and new technologies before you know it.

For a more gentle introduction to the future of radical life extension via medical nanotechnology, you might want to read Chris Phoenix's "Nanotechnology and Life Extension."

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Yet More Reasons To Exercise
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We don't know how long it will take for science and business to develop and deliver working rejuvenation therapies capable of reversing age-related damage and significantly extending our life spans. So it makes sense to take the best possible care of ourselves today - the longer you live in good health, the more likely you are to benefit from the future of medical technology. With that in mind, take a look at what the Scotsman has to say about exercise and neurodegeneration: "Middle-aged people can reduce their risk of developing dementia and Alzheimer's disease later in life by remaining physically active, according to a new study. Researchers found people who exercised at least twice a week in sessions lasting 20 minutes or more reduced their risk of developing Alzheimer's disease by 60 per cent, compared with those who did a small amount of training. The active group also lowered their odds of having dementia by 50 per cent."

Link: http://news.scotsman.com/health.cfm?id=2040382005

More On Hair Stem Cells
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Researchers have been moving steadily towards stem cell based regenerative medicine for hair over the past few years. From EurekAlert we have more signs of progress: "In 2001, Barrandon was part of a French research team who reported in the scientific journal Cell that stem cells could be used to generate skin containing hair and sebaceous glands in mice. But at that time it was unclear whether the stem cells in hair follicles were true stem cells, capable of long-term renewal, or multipotent progenitor cells that would not permanently engraft in the follicle. ... Swiss researchers have answered that question, using rat whisker hair follicles to demonstrate that the clonogenic keratinocytes in hair follicles are true stem cells. ... With the progeny of a single stem cell, it would be theoretically possible to generate the complete hair bulb of a human being, and one that would last for years."

Link: http://www.eurekalert.org/pub_releases/2005-10/epfd-hsc100505.php

Biochemical Tinkering for Increased Life Expectancy
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Here's a little slice of recent scientific history for today via GRG mailing list. The capabilities of biotechnology continue to improve, and scientists are mapping and understanding ever more of the complex web of human biochemistry and genetics. As this process continues, I think we'll see many more proposals along the lines of the conclusion to this PDF-format scientific paper from 2004 on angiotensin I-converting enzyme (ACE). The authors connected this particular small component of human biochemistry to a range of age-related conditions and concluded:

Genomic epidemiologic data, increasingly supported by clinical outcomes results, strongly suggest that overactivity of angiotensin I-converting enzyme (ACE) may underlie most age-related diseases. Angiotensin II, the main product of ACE, is a pleiotropic hormone, capable of serving as a neurotransmitter, growth factor, angiogenesis factor, vasoconstrictor, pro-thrombotic agent, and cytokine. So it is perhaps not surprising that the ACE DID genotype is associated with several major psychiatric diseases, most cancers except prostate cancer (where the DID genotype is actually protective), most cardiovascular diseases, most autoimmune diseases, and even infectious diseases like tuberculosis and HIV.

...

For example, calorie restriction prolongs life-span in a number of species. With less fuel consumption, mitochondrial electron transport and production of ROS are decreased. sACE overactivity as a cause of aging is entirely consistent with this model, since angiotensin II stimulates mitochondrial electron transport, oxygen consumption, and production of ROS. Chronic angiotensin II signaling leads to mitochondrial hypertrophy and proliferation. Eventually, angiotensin II leads to mitochondrial dysfunction, with increased uncoupling of electron transport from A TP synthesis, and increased production of ROS. Inhibition of ACE in old animals restores mitochondrial function.

...

In summary, population morbidity and mortality should be significantly reduced, and longevity enhanced, by widespread use of an ACE inhibitor or ARB. The only caveat is that white men taking an ACE inhibitor or ARB will need to check their PSA at least once a year.

The authors may have been overreaching, although the mitochondrial connection is especially interesting in light of what we presently know, but I think we'll be seeing more of this sort of review and proposal in the future. Understanding a system implies understanding how to fix and improve that system - and an increased understanding is certainly one of the things we need in the fight to cure aging.

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Similar Mechanisms Mean Faster Research
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Good news from Betterhumans: scientists have found that another longevity gene exists in mice as well as nematode worms. The more mechanisms of aging are similar between species, the more rapidly basic aging research can proceed - this is because it is much cheaper and faster to work with worms, flies and yeast than with mice or other mammals. If work in lesser organisms has greater value, then this is good news for us. From the article: "the longevity-promoting effect of reducing clk-1/mclk1 activity that was initially observed in C. elegans is conserved in mice, supporting the idea that some molecular mechanisms of aging are shared throughout the animal kingdom."

Link: http://www.betterhumans.com/News/4685/Default.aspx

On Telomerase
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The latest article from SAGE Crossroads focuses on telomerase: "Like a next-door neighbor who turns out to be a spy, a protein once thought to mete out life span is doing a few surprising things inside its cellular home. Telomerase, a cellular operative made of protein and RNA, keeps chromosome ends from shrinking each time a cell divides. Researchers used to think that this erosion could drive organismal aging. Although this idea has largely fallen out of favor, many scientists hold that corroding telomeres might hasten the demise of tissues and organs ... Now, a clutch of studies reveals that telomerase's talents go beyond replenishing the far reaches of our chromosomes and might include stimulating stem cells to replace tissue."

Link: http://www.sagecrossroads.net/Default.aspx?TabID=28&newsType=ArticleView&articleId=133

Animals Gain First Access to the Best New Medical Technology
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New medical technologies have a way of becoming commercially available for veterinarian use long before we humans have a shot at it. This is largely because the veterinary world has no real equivalent to the destructive influence of the FDA (and its overseas cousins). New medical technologies for use with animals are developed and commercialized in an environment that - even though overregulated - more readily rewards effectiveness, time to market, a good grasp of risks involved and economic viability. The entrenched interests in human medicine, as in all centralized, largely unaccountable systems, have become dangerously ineffective. Hence dolphins gain access to reconstructive tissue engineering and stem cell therapies, as do horses:

For the past three years, Prof Roger Smith and his team at the Royal Veterinary College in North Mimms, Herts, have recovered stem cells from bone marrow and used them to treat more than 160 horses.

About a third of National Hunt racehorses injure the digital flexor tendons at the back of the lower leg. In the new treatment, a damaged tendon is rapidly "repopulated" by flexible new tendon tissue, rather than leathery scar tissue that naturally forms over a period of up to 18 months.

About 70 per cent of treated horses have returned to racing form - more than double the percentage that would be expected had they received conventional treatment.

Something must be done about the oppressive regulatory regime in Western countries that slows commercialization, blunts the incentives for success, reduces effectiveness and increases costs for human medicine. If good, working regenerative medicine is possible in dolphins and horses, then it is certain possible in people.

The Logic Of Calorie Restriction
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The Times is running a good article on calorie restriction and its potential as a tool to extend the healthy human life span. "Of course, I can't tell you if my subjects will live to 130. So many uncontrollable factors affect length of life. I don't have enough evidence to prove these people are ageing more slowly, but it looks like it. ... No one wants to die now. So why think you'll feel different at 80? I want the extra years CR can offer. If I get to 110, then they may have tools that will fix ageing. A kind of rejuvenation procedure. People may call me obsessive, but this is logical behaviour." Very logical: your best shot at radical life extension is to stay ahead of the medical technology curve, by using the best presently available techniques and helping to accelerate healthy life extension research.

Link: http://www.timesonline.co.uk/printFriendly/0,,1-100-1806237-142,00.html

Profiling Kenyon, Nematode Worms
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The Pittsburgh Post-Gazette profiles Cynthia Kenyon's work on extending the life span of nematode worms: "Aging doesn't occur simply because parts wear out, but also because our genetic code is programmed to reduce the body's repair work after a certain age. ... Dr. Kenyon showed that tweaking a gene called daf-2 'in just the right way' resulted in extraordinary increases in lifespan. ... adjusting the action of daf-2 in roundworms can extend life even if this tweaking doesn't occur until the worm has reached mid-life. Again, no one can say whether this applies to humans, but it has to be encouraging for anyone facing a mid-life crisis. ... How soon any of this can be translated into a hormone or drug therapy that extends life is not clear."

Link: http://www.post-gazette.com/pg/05276/581565.stm

Government as Enabler
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Governments large enough to interfere in any aspect of life produce this effect: any comparatively small group can leverage its resources through government (by buying politicians or legislation, by steering tax dollars or fiat government funds) to produce a far greater effect that its members would otherwise be capable of. We see this happening for progress in medical research on a constant, ongoing basis; it is hampered and slowed by the actions of successful influence groups who oppose technological progress, either deliberately (no embryonic stem cell research or therapeutic cloning) or incidentally (let's run everything by centralized control). On the other side of the coin, you can see the same process going on for pro-research groups. Both sides waste resources profligately on steering notoriously inefficient government efforts rather than getting things accomplished themselves - it becomes an arms race, a race to the bottom in wasting donated resources to fight over taxed or fiat resources, rather than simply utilitizing donated resources directly. The lesson you should take away from a recent Virginia Postrel article on opposition to progress has nothing to do with right or left, corporations or activists, despite her framing of the issue:

You can't say the same for the antibiotech left. In liberal Canada, in fact, the law defines cloning expansively. Future procedures that might avoid religious objections would still be illegal. The goal is to stop certain research altogether.

That may sound strange to Americans. To many liberal Democrats reproductive choice and scientific progress are touchstone values. But they aren't the only values on the activist left. For many environmentalists, most famously Bill McKibben and Jeremy Rifkin, tampering with genetic nature is inherently wrong. How you do it is a minor detail.

Some feminists object to egg donation, paid or unpaid, for research or conception. "It presupposes an instrumental attitude toward one's own body and that of others" and begins to impose a "social obligation on the female body," notes German feminist Ingrid Schneider.

Genetic research also offends egalitarians. They fear that the rich will benefit first or that money for research will come from social programs. Social justice, argues Marcy Darnovsky of the Center for Genetics & Society in Oakland, Calif., "means not just 'no designer babies,' but also 'no designer medicine.'"

These intellectual influences are stronger in Europe (and Canada) than in the U.S. But two equally threatening ideas do crop up frequently among mainstream Democrats: that commerce taints medicine (those evil drug companies!) and that any activity that has social consequences ought to be centrally regulated.

The real problem is not that some people dislike progress and are willing to try and convert or impose upon others - there will always be people like that. In a free world, they would be able to buy their own land and live as they like, and their influence would only scale by their numbers. Rather, the problem is that leverage of the enormous, unaccountable resources of modern governments a) allow otherwise marginalized anti-research, anti-progress groups to greatly damage our prospects for health and longevity and b) drag pro-research groups into what is ultimately a wasteful, less efficient employment of resources. The problem isn't people, it's the concentration of power.

It is precisely this concentration of power - and the political battles that come with it - that compels patient advocates, supporters of regenerative medicine, healthy life extension research and other proponents of freedom in medical science to generate widespread public support for their common cause. Widespread support has other merits and benefits, but it is a needed defense in a world in which your efforts can be greatly harmed by an errant, misdirected government.

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Deciphering Arthritis
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(From EurekAlert). Scientists are making good progress in following the biochemical chain of events back to the root cause of arthritis - and other autoimmune and inflammatory conditions: "a novel type of "T helper" cell [is] the culprit for initiating chronic inflammation and autoimmunity in a variety of body tissues. This newly described T cell - which they call inflammatory TH cells (or THi) - produces interleukin 17 (IL-17), a potent cytokine that researchers have already linked to an immune system gone awry. ... These findings suggest that shutting down the activity of these THi cells might stop chronic inflammatory diseases from developing in the first place." Tests of first generation gene therapies for arthritis have already taken place; the next generation should be much more effectively targeted and efficient.

Link: http://www.eurekalert.org/pub_releases/2005-10/uotm-nic093005.php

CIRM Stem Cell Conference Underway
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As reported by the San Franciso Examiner, the first scientific meeting of the California Institute for Regenerative Medicine is presently underway. "The two-day conference will feature some of the most renowned stem cell researchers in the world and is aimed at forming research strategy for the institute, which will hand out $3 billion in scientific grants over the next decade." That is if the political battles ever end; even the process of bond issuance is bogged down in legal attacks by anti-research groups. But back to the science: "University of California professor Dr. Hans Keirstead - best known for enabling paralyzed rats to walk again by injecting them with human brain cells - will be speaking Sunday about his recent discovery in generating human embryonic stem cells that are pure enough for research."

Link: http://www.sfexaminer.com/articles/2005/09/30/news/20050930_ne03_stemcell.txt

Life Expectancies Still Increasing
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Actuaries are generally on the conservative end of aging research, but you'll still see a recognition of the prospects for healthy life extension in their work. The BBC has the latest: "The life expectancy of men who are 65 may rise by another three years during the next decade to nearly 90. ... For the first time, the authors of the actuaries' continuous mortality investigation (CMI) have refused to make an official projection of future life expectancy based on their new mortality research." A continuing rise in life expectancy is to be expected as medical science advances; our bodies are simply complex machines, so better repair and maintenance techniques lead to longer, healthier lives. Still, this incidental healthy life extension is a slow process - directed research into repairing the root causes of aging would be much faster.

Link: http://news.bbc.co.uk/1/hi/business/4295362.stm

Think Tanks Thinking
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The Demos group, a UK think tank, is attempting to stimulate public debate on human enhancement, including healthy life extension and the development of working anti-aging technologies. "The aim of this project is to initiate a public debate about issues of human enhancement in the UK. We'll be commissioning a series of essays from different perspectives about the implications of human enhancement to be published as a Demos collection in January 2006." Given the nature of these sorts of groups, the result is likely to oppose freedom to research and use medical technology - and just plain freedom for that matter - with all the normal flawed thinking on regulation, choice and the role of government in people's lives. That said, when more discussion of healthy life extension takes place, more people are likely to decide to support it.

Link: http://www.demos.co.uk/projects/currentprojects/betterhumans/

SENS 2 Report: Moving Mitochondria
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Frank Rummel has another of his SENS 2 reports up for your reading pleasure. This time, the focus is on progress towards copying mitochondrial genes into the cellular nucleus - this is one of biomedical gerontologist Aubrey de Grey's proposed strategies for mitigating age-related cellular damage. Mitochondrial DNA is essential to the functioning of our cells, but is damaged much more readily than nuclear DNA; this damage is implicated as a cause of a range of age-related degenerative conditions.

Dr. de Grey says,"Rather than fixing mitochondrial mutations, we can obviate them. We can make copies of those 13 genes and put these copies into the chromosomes in the nucleus. Then, if and when the mitochondrial DNA gets mutated so that one or more of the 13 proteins are no longer being synthesised inside the mitochondria, it won't matter -- the mitochondria will be getting the same proteins from the nucleus."

This is exactly what Dr. Weiner has done; the frst case of one of these 13 mitochondrial proteins in particular having the gene for making it expressed in the nucleus rather than in the mitochondrial DNA. More details can be found in Professor Weiner's abstract of his SENS 2 presentation entitled "Factors that might affect the allotopic replacement of a damaged mitochondrial DNA-encoded protein".

...

Professor Weiner cautioned me that they had worked with the easiest case of the 13 mitochondrial component proteins, and that the remaining 12 would be much more difficult to solve because they are so difficult to get at. In very simple terms, working with the 13 is complicated by the fact that simply pulling aside what surrounded what you are trying to get at jeopardized the very thing you were trying to get at due to the complexity of all the interactions involved.

But still, that's a promising step forward. Another strategy for dealing with damaged mitochondrial DNA is to replace it with fresh, new, undamaged DNA - a more conventional task of repair for those of us familiar with everyday machinery. At least one group has achieved early success in developing the tools needed to perform this repair, using a technique called protofection.

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