Back To Calorie Restriction
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As you may know, researchers Michael Rose and John Phelan have joined the ranks of those marshalling scientific arguments against calorie restriction (CR) as a means of significantly extending healthy life span in humans - "significantly" in this case meaning by a few decades. Regardless of the merits of their paper and models - from the discussions on the GRG mailing list, they form a good stab at the topic, but are far from watertight - I think that we should remember that we're talking about something that can, at best, assuming folk like Michael Rose are wrong, slow aging by a handful of years. This is far, far better than nothing - and indeed, I'm very much the calorie restriction advocate - but it pales before what would be possible in the years ahead if sufficient funding were devoted to developing real anti-aging medicine.

I've said before that too much time, attention and money is spent chasing the slowing of aging rather than reversal of aging. I also think that Randall Parker is right on the money with his comments:

We need rejuvenation therapies. The idea of finding a way to slow aging with CR or sirt1 or the latest hope Klotho all seem like misplaced hopes to me. Klotho may eventually deliver the same (limited) benefit as CR but without the perpetual hunger and might be worth taking some day. But we really need gene therapies, cell therapies, immunotherapies that can remove extracellular junk, and other therapies that can do repair.

Calorie restriction is good for you, and is currently the best, most backed method for extending your healthy life span. Yet this is only true because there are no other available methods ... and calorie restriction isn't the starting place for the healthy life extension medicine of the future. That starting place is funding for medical research programs like Aubrey de Grey's SENS - and lots of it.

To Repair The Aging Ear
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From the LEF News, a look at one set of efforts to repair age-related deafness: "A New Mexico State University researcher is studying sensory cells in the ear in hopes of finding treatments to restore destroyed cells, which can cause hearing or balance problems. ... sensory cells that look like hairs [perceive] the force of sound to allow hearing and the force of gravity to maintain balance ... When things such as noise, mutated genes or aging destroy the cells, they don't regenerate in humans. ... If scientists identify the gene that creates hair cells, they might be able turn it on to make another type of cell become a sensory cell." This is early, investigative work, but a good example of avenues in regenerative medicine opened by better tools and greater understanding of genetics.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2639&Section=AGING

Mechanics Of Tissue Engineering
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Researchers are making good progress in improving the techniques of tissue engineering, as this Innovations Report article illustrates: "Repairing major damage to the derma is a difficult problem facing plastic surgeons. But now researchers at Linkoping University have hit upon a highly promising method. By injecting tiny balls of gelatin, they have managed to get various types of cells to grow spontaneously in the areas where new tissue needs to be generated. ... All types of cells attempted grew extremely well in the gelatin balls: skin cells, connecting tissue cells, cartilage cells, early stages of fat cells, and mammary gland cells. Experiments with transplanting in mice also yielded favorable results. Injection under the skin of spheres containing connecting tissue cells and fat cells led to good regeneration of tissue."

Link: http://www.innovations-report.com/html/reports/medicine_health/report-48452.html

Root Causes of Late Adopter Preference
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As you may know, I'm a big fan of late adoption and conservatism (in the "marked by caution and moderation" meaning of the word), as well as patience and a wide field of view when looking at science in progress. With that in mind, I thought I'd point you to a very helpful look at why my point of view is a good one.

"There is increasing concern that in modern research, false findings may be the majority or even the vast majority of published research claims," says researcher John Ioannidis in an analysis in the open access international medical journal PLoS Medicine.

This is something that scientists are quite aware of - although you wouldn't find many broadcasting it to the world, for all the obvious social reasons. I think it's a wonderful exercise to point out the systematic causes of this process. When I said the following:

Important questions, especially those related to medicine and statistics, are not answered with a single study. Each study, and the resulting debate, can take years. Building - or changing - even a preliminary scientific consensus on any position is a process that spans decades.

I could - and should - have added that most of what was written on these topics would turn out to be wrong. It might contain useful ideas, or prompt other people into useful directions, but it will be wrong. This is taken for granted by scientists; after all, the scientific method and the community that supports it form a system that makes useful, rapid, solid progress even though the individual components of that progress are largely flawed. Science is built by consensus and aggregation, a form of ongoing, distributed cross-checking of information. Every single collection of data could be 99% wrong, but you'll still get the right answer in the end if you have enough of those collections to compare.

The take away here is not to listen to any single study (and especially if someone is using it to sell you something relating to the anti-aging marketplace). Ten studies or twenty studies pointing to the same conclusion are more interesting.

Good News For Progeria Sufferers
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Research into progeria, an accelerated aging condition, has improved our understanding of normal aging. It is good to hear that scientists have made unexpectedly good progress towards a therapy that addresses the biochemistry of progeria: "farnesyltransferase inhibitors (FTIs), originally developed for cancer, are capable of reversing the dramatic nuclear structure abnormalities that are the hallmark of cells from children with progeria. This is a stunning surprise, rather like finding out that the key to your house also works in the ignition of your car." This discovery comes a mere two years after "researchers in Francis Collins's lab at the National Human Genome Research Institute discovered that mutations in the lamin A (LMNA) gene cause" progeria. Such rapid progress in medical research is a striking sign of the times - and very promising.

Link: http://newswire.ascribe.org/cgi-bin/behold.pl?ascribeid=20050826.125117

More Bone Tissue Engineering
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(From LocalTechWire). It is good to see that progress is being made in the tissue engineering of bone with a range of different approaches - variety is a sign of a healthy field. "Dr. Elizabeth Loboa's research at the North Carolina State University cell mechanics laboratory uses a unique approach to create bone tissue from adult stem cells. Loboa, assistant professor of biomedical engineering, and her research assistants are growing bone tissue. The process uses fluid shear stress applied to human mesenchymal stem cells (hMSCs) that have been seeded into a polymeric scaffold. ... the team believes that this discovery could lead to clues about how mechanical stimuli modulate hMSC differentiation into bone." This is a clever approach to controlling stem cell behavior.

Link: http://www.localtechwire.com/article.cfm?u=12171

13th Foresight Conference
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Healthy life extension supporters will no doubt be interested to hear that biogerontologist Aubrey de Grey will be speaking at the 13th Foresight Conference on nanotechnology next month. You may recall that de Grey provided the expert opinions for the Foresight Challenge on using nanotechnology to increase human health and longevity. As the press release says, "The Vision Weekend provides a rare opportunity to hear speakers including Peter Diamandis of X Prize Foundation, Aubrey de Grey of University of Cambridge, Eric Drexler of Nanorex, and Richard A.L. Jones, University of Sheffield, discuss the future of nanotechnology candidly and off-the-record." All good, clean fun for those of us who look forward to a future of advanced nanomedicine capable of supporting radical life extension.

Link: http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20050829005638&newsLang=en

Towards Tissue Engineering
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Wired reports on European efforts to collaborate and move ahead with tissue engineering: "The $32 million project, funded by the European Union, gathers 23 of Europe's leading companies and research centers from 13 countries. ... The project hopes to give biomedical companies the jump start they need to turn a profit through tissue-engineering technologies ... Despite plenty of progress, tissue engineering has not achieved tremendous clinical success or commercial success. At the moment we can successfully produce a very small amount of tissue, but nothing good enough to replace large areas of skin or cartilage. We want scale up the process. ... The partners will work on a wide range of problems in parallel, tackling the logjams that face commercial tissue engineering."

Link: http://www.wired.com/news/medtech/0,1286,68590,00.html

Folding@Home Team Hits Rank 500
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Congratulations are due to to the members of the Longevity Meme Folding@Home team, who have pushed us past rank 500 in such a short time. What is Folding@Home? It is a program by which folks like you and I can team up to compete in the donation of spare processing time from our computers to advance the understanding of protein folding - vital to tackling age-related conditions such as Alzheimer's disease. As promised, I will be mailing out mementos to those members who joined prior to August 28th, 2005: if you are one of them, please do send an email with "Folding@Home 500" in the subject line to let me know a) your mailing address and b) your Folding@Home username.

Link: https://www.fightaging.org/archives/000588.php

Optimism, Pessimism, Tempered
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For today, a post wherein I reproduce part of an exchange from the GRG mailing list. Robert Bradbury (who has some interesting ideas on aging that you might want to read) is presently in an optimistic frame of mind based on a look back at the past decade:

Some of you may want to do a PubMed search on: genes AND aging. It now turns up more than 5600 articles. That would have been a *much* smaller number in the mid-to-late '90s.

Of particular interest on the first page are the articles by C. Kenyon reporting on aging genes in C. elegans, S.M. Jazwinski on aging in yeast, J. Campisi on cell senescence and cancer and D.C. Wallace on the involvement of mitochondrial mutations in somatic cell aging.

These are all some of the leading researchers in aging studies.

The article by C. Kenyon is particularly important as they used an RNAi library to identify 23 new longevity genes in C. elegans.

Given the recent transgenic mouse studies extending the lifespan by using retargeted catalase (Rabinovitch) and the Klotho study (Kuro-o) it seems likely that transgenic mouse studies of longevity will increase significantly. But transgenic mouse studies are long and expensive (though there appear to have been tens of thousands of them which have been done). Now that the Zebrafish [genome] map is essentially complete it is possible to use them as a vertebrate model for aging. Though they live longer than mice it is much cheaper to create transgenics in a wide variety of genes (many more eggs at very low cost) and study internal physiological changes that take place with age (they are transparent). There are also very low costs for keeping thousands of them which is something not usually done with transgenic mice.

These things combined lead me to the conclusion that we are entering the "golden age" for understanding aging. By 2010 we should have a fairly good understanding of all of the significant causes of aging and by 2015 have probably developed a number of interventions for human beings to be tested in human beings.

One of the debates will revolve around whether those interventions should be transgenic manipulation of cells (either in vivo or using stem cells) or whether they will be through drug companies providing drugs.

So the chances of anyone aged 55 or younger of having a significantly extended lifespan over the current average lifespan seems quite high in my opinion.

He is right in that the basic research is moving forward very nicely, but I'm a little less optimistic at the moment. This is partially a result of my libertarian concerns regarding regulation and partially a result of where I see the research funding going at the present time:

The thing that bothers me is that I see all the presently engaged money sliding down the slope to the "slow aging" end. The range of plausibles down there - metabolic tinkering, lifelong gene alterations, etc - don't appear to include interventions that will do much good for us folks who used up 2/3 or more of our damage quota by the time they're introduced.

We need, ASAP, significant resources heading upslope to SENS-like strategies aimed at reversing the damage of aging. If by 2020 the best that's available is along the lines of super-[calorie restriction] or super-Klotho in humans that will produce 30% life span extensions for those who benefitted from them for an entire life, I fear we oldtimers will be out of luck.

I make the same cautions a little more clearly in the latest Longevity Meme newsletter:

There is no such thing as useless information in cellular biochemistry, but practical anti-aging medicine for those of us who have burned through two-thirds or more of our life already will probably not come from comparatively modest tweaks - genetic or otherwise - to metabolic processes. All these do is slow the rate at which age-related damage accumulates, something that decreases in utility the later in our lives it starts.

I don't see it as implausible that longevity science could vanish down the rabbit hole of producing a better calorie restriction or a better klotho - something that would be wonderful and effective for people with their whole life ahead of them, but singularly useless for those of us reading this today. It's up to us to ensure that this does not happen: the time to influence the directions and emphasis of longevity research is now, just as it always has been. You can have your say in the matter by donating to the rejuvenation (or late intervention) component of the Mprize, which rewards scientists who work on anti-aging science specifically designed to save the lives of the aged. If we fail, we'll be left looking just like the last generation of healthy life extension supporters and advocates - and that would not be a good thing, not at all.

Michael Rose On Calorie Restriction
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(From Reuters AlertNet). Biologist Michael Rose, known for his work on aging in flies, is a calorie restriction (CR) skeptic, it would seem. He and John Phelan have developed a mathematical model that predicts a "lifetime of low-calorie dieting would only extend human life span by about 7 percent, unlike smaller animals, whose life spans are affected more by the effects of starvation. ... Longevity is not a trait that exists in isolation; it evolves as part of a complex life history, with a wide range of underpinning physiological mechanisms involving, among other things, chronic disease processes." I'm sure this will kick off another active discussion on just how to measure the effects of calorie restriction on human longevity without waiting and counting years, but it's safe to say that the numerous health benefits of CR are well proven.

Link: http://www.alertnet.org/thenews/newsdesk/N28161982.htm

Longevity Meme Folding@Home Team Hits Rank 500
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Congratulations are due to members of the Longevity Meme Folding@Home team; they've worked, posted, recruited and donated - and pushed the team rank from 700 to 500 in a mere ten weeks since I last gave an update. As promised, I will be mailing goodies to those participating members who want a memento of the occasion. If you joined the team prior to today (August 28th 2005), send me an email with "Folding@Home 500" in the subject line and containing the following information:

  • your mailing address
  • your Folding@Home username

Well done! Here's to hitting 300 in another ten weeks.

Readers who are not familiar with the Folding@Home program - in which you donate spare processing cycles from your computer, to be used in investigations of the biochemistry of Alzheimer's and other conditions related to protein folding - may want to start with my introduction at the Longevity Meme.

As In Lizards, So In Mice
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Very good news for the branch of regenerative medicine that attempts to mimic the ability of certain lizards to regenerate entire body parts. The Australian reports that researchers "have created 'miracle mice' that can regenerate amputated limbs or damaged vital organs, making them able to recover from injuries that would kill or permanently disable normal animals. The experimental animals are unique among mammals in their ability to regrow their heart, toes, joints and tail. And when cells from the test mouse are injected into ordinary mice, they too acquire the ability to regenerate." It appears that this is "controlled by about a dozen genes. Professor Heber-Katz says she is still researching the genes' exact functions, but it seems almost certain humans have comparable genes." Wow. Full details to be presented at the SENS conference.

Link: http://www.theaustralian.news.com.au/common/story_page/0,5744,16417002%255E30417,00.html

Stem Cell Therapy For Heart Attacks
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Mrytle Beach Online carries wire reporting on an first generation adult stem cell therapy for heart attack victims practiced in Japan: "The patient's heart function recovered to the extent that he could live without the artificial heart. ... Under the treatment, bone marrow cells are extracted then transplanted into the damaged ventricle of the heart. ... Researchers are still unsure how bone marrow cells transplanted into the heart work. Further studies are needed to determine whether stem cells contained in bone marrow transform into cardiac muscle cells or blood vessel cells, or whether stem cells simply assist cardiac muscle cells to develop." They seem set to carry on: "I believe that we've established a treatment that is safe and side-effect free. The treatment will save patients who are unsuitable for transplants. We intend to use this treatment in clinical practice."

Link: http://www.myrtlebeachonline.com/mld/myrtlebeachonline/news/world/12494617.htm

The Diseases Of Civilization
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From Medical News Today, a concise explanation as to why excess food and inactivity are very bad for our healthy and life span. "Human beings are genetically adapted to conditions of scanty and irregular nutrition. In case of food abundance this advantage turned into a significant part of population's predisposition to 'diseases of civilization'. ... During the era of civilization, the major part of mankind passed to abundant nutrition without starvation periods which were quite natural previously and without significant spending of muscular energy." This change in usage of the complex biochemical machinery of our bodies leads to common age-related disease, suffering and shortened life spans. Fortunately, all of this is within our ability to control - exercise, supplementation and calorie restriction are your friends.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=29755

A One-Time Diversion to the World of Weight Loss
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I advocate calorie restriction (CR) as a Good Thing, assuming your physician agrees, as I'm sure regular readers know by now. The health benefits have been more than adequately demonstrated, and there is the strong likelihood of increased longevity based on decades of animal studies and a few tantalizing human results. Of course, you'll also lose weight - but this is something of a side-effect for CR practitioners rather than a goal to be attained for its own sake. Since starting my advocacy of CR, I've heard numerous anecdotes regarding the difficulties that more overweight - or obese - people have with the practice of CR; it seems that different dietary and lifestyle strategies are more effective at weight loss above a certain weight (varying by person). Once you get down to a more reasonable weight, calorie restriction becomes easier. Or so they say.

While wandering the wilds of the web today, I came across a summary of a much more rigorous treatment of this phenomenon and thought it worth sharing.

Without hard data, I've relied on the idea that the Basal Metabolic Rate (BMR) in metabolism may be the trigger for a "conservation of energy" in the human body. That taking daily calories below the BMR triggers what many call "starvation mode" in the metabolism - that is, the body starts to use less energy as it prepares to survive what it perceives as a famine condition.

My recommendation has remained consistent over the years - one must try to determine their BMR and eat enough calories to meet that calorie requirement for basic function so the body will allow for loss of its stored energy - fat on the body. Interestingly, the BMR of most people is much higher than they realize and certainly higher than the often recommended calorie-restriction of 1200-1600 calories per day for weight loss.

The article goes on to discuss and explain the significance of a recent study on some biochemical details of calorie restriction and weight loss. Interesting stuff. The information to take away with you would seem to be that at a given weight, there is an optimal level of caloric intake that will convince your body to process stored fat rather than hoard it or layer on more. The more fat you have, the more calories you need in order to hit this optimal intake. If this level is much higher than the level of caloric intake for an out-of-the-box practice of calorie restriction, then you will likely have difficulty jumping right on in. A more gentle ramping down of calories might be called for, as well as trial and error testing of your metabolic response to different levels of caloric intake - as more experienced calorie restriction practitioners would advise in any case. As with many other things, patience, research and experimentation will win through in the end.

If you're new to calorie restriction, I recommend picking up a copy of The Longevity Diet; I think you'll find it very helpful.

My final, anecdotal, contribution: regular exercise makes all the difference to your efforts, leading to large changes in the response of your body to different levels of caloric intake. Try it and see.

Klotho Revisited
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MSNBC has one of the better popular articles on the latest study of the Klotho gene in mice. Those of you with longer memories may recall that Klotho was first associated with longevity and the aging process - in both humans and mice - a few years ago. Now scientists have established that overexpression of Klotho in mice extends life span by a good 20-30%. "You have lots of ways to shorten the life of an animal, but it's hard to get an animal to live longer. You can kick a radio to make it not work so well, but it's hard to make it work better. It's quite a wonderful discovery." A curmudgeonly caution: this, like calorie restriction research, is basically a way of tuning our complex metabolic machinery for better performance over time. It's not anti-aging medicine to the level of SENS or similar proposals.

Link: http://msnbc.msn.com/id/9079798/

Fear Of Death And Muddled Thinking
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Robin Hanson has put up an interesting PDF-format paper on how the fear of death leads people to do precisely the wrong things to extend their healthy life spans. "Humans clearly have trouble thinking about death. This trouble is often invoked to explain behavior like delays in writing wills or buying life insurance, or interest in odd medical and religious beliefs. But the problem is far worse than most people imagine. Fear of death makes us spend fifteen percent of our wealth on medicine, from which we get little or no health benefit, while we neglect things like exercise, which offer large health benefits." People are also failing to understand and support the best branches of research into working anti-aging medicine - lack of foresight and planning for the future in this matter is not good.

Link: http://hanson.gmu.edu/feardie.pdf

On Klotho
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The Klotho gene (link to Wikipedia, a stub entry at the time of writing that I expect to see expanded) was under investigation back in 2001 and 2002 for its association with longevity:

Studying more than 2,000 anonymous samples from three ethnically distinct groups of people, the scientists found that having two copies of a less-common version of klotho is twice as prevalent in infants as in people over age 65. These results suggest that people born with the two copies die sooner than others, although the gene's exact influence on health and aging are not known, the scientists say.

...

Previously, Japanese scientists discovered klotho in mice, noticing that without klotho's protein, the mice developed atherosclerosis, osteoporosis, emphysema and other conditions common in elderly humans. Because of their interest in accelerated aging diseases, Dietz and his colleagues began studying klotho in people.

The first thing to do when you discover a mechanism that accelerates age-related degeneration in mice is to turn it around and see if can extend healthy life span - as a general rule, gerontologists are unexcited by processes that reduce life span. There are all too many of those, and most have no association with any way of extending life span - application of blunt force is one example, as a certain wag noted.

The time elapsed between the 2002 work and the present day is just about long enough to set up a decent set of life span experiments with laboratory mice and get a good sense as to how it will all turn out. In the case of the Klotho gene, this indeed came to pass. It is pleasing to see that Klotho has now been welcomed into that small, select circle of known ways to significantly extend healthy life span in mice:

In the new study, a group led by Kuro-o, now an assistant professor of pathology at the University of Texas Southwestern Medical Center at Dallas, created transgenic mice with overactive versions of the Klotho gene. Those mice proved to have life spans 20 percent or more longer than mice with the ordinary version of the gene, Kuro-o said.

"These are still animal experiments, but potentially it might be possible to use the hormone in humans," he said. "But we still don't know if the protein can be used to extend life span in humans."

A lot must still be learned about the Klotho hormone, starting with the way it works, Muro-o said. "We speculate that it blocks insulin action," he said. Specifically, it appears to block the insulin-like growth factor-1 pathway. Studies have shown that blocking that pathway extends the life span of worms, flies and mice, he said, and the same may well be true of humans.

The upper bound of life span extension in the study was 30% or so, in the same ballpark as the results of calorie restriction. The association with insulin suggests that both overexpression of Klotho and the gene expression changes caused by calorie restriction may work on an overlapping set of biochemical mechanisms - which certainly shouldn't prevent industrious researchers from trying both at once to see how that goes. I certainly would if I had the funds and a group of gene engineered Klotho mice.

I predict that this will be grist for the mill for those funded groups and companies - such as Elixir, Sirtris, etc - already working hard on metabolic science resulting from calorie restriction studies. Good news all round for those interested in near term (next five to ten years) results from currently funded longevity research.

UPDATE: I should have mentioned that Kevin Perrott has more on Klotho; I certainly agree that researchers should enter a set of Klotho mice into the Mprize for anti-aging research.

Wired On Calorie Restriction
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Wired is carrying a mixed article on calorie restriction (CR); while they managed to find my comments at Fight Aging! on Aubrey de Grey's views of CR, it seems they missed the human studies demonstrating impressive health benefits. Sadly, the piece fixates on the normal (circa 2000, that is) mainstream media talking points related to eating less for health reasons. Still, CR is making headway in public awareness: "With the oldest members of the baby boomer generation about to turn 60, demographic trend watchers aren't surprised to see a rise in interest surrounding diet and health pursuits associated with extending life expectancy ... caloric restriction, an age-extending technique that has been shown to work quite well on mice and other organisms, is an increasingly popular option."

Link: http://www.wired.com/news/print/0,1294,68562,00.html

The Slow Spread Of Ideas
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The ideas of healthy life extension - and the notion that we are close to greatly extending the healthy human life span, if only the funding were there - arrive but slowly in some quarters. The Washington Post illustrates this point with an article on changes in retirement and work at later ages - miniscule changes in the grand scheme of what is to come, but still unwelcome news to some people. I think this fact illustrates the current set of problems well: "In the late 1920s, the chief actuary of the Metropolitan Life Insurance Co. put a cap of 65 on life expectancy." The same blindness to advancing medical technology - even in the absence of major investment in the development of working anti-aging medicine - is at work now. Change is coming, and since it'll involve longer, healthier lives, how can it be bad?

Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/08/23/AR2005082301175.html

The Long Tomorrow
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Researcher Michael Rose's new book is out, entitled "The Long Tomorrow, How Advances in Evolutionary Biology Can Help Us Postpone Aging." From the blurb: "The conquest of aging is now within our grasp. It hasn't arrived yet, [but] a scientific juggernaut has started rolling and is picking up speed. A long tomorrow is coming. ... Michael Rose is more qualified than anyone currently working in the field of aging to write about the evolutionary development of aging in biological organisms, and he presents us here with a clear, easy-to-digest overview of the field. We meet the leaders and the busy-bee scientists; the believers and the nay-sayers. His final summary of the possibilities for postponing human aging is one of the most accurate and believable to appear in recent years." You may recall that Rose penned one of the essays in the Immortality Institute's "Scientific Conquest of Death."

Link: http://www.us.oup.com/us/catalog/general/subject/LifeSciences/EvolutionaryBiology/?view=usa&ci=0195179390

Brain Metabolism, Alzheimer's
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I found this HHMI research into brain metabolism and Alzheimer's rather interesting, especially in light of another recent piece on changes in gene expression in the aging brain. Alzheimer's disease appears to be like rust - you can certainly put it off, you may be lucky enough to have moderately rustproof genes, but live long enough and you'll get it eventually ... and it will kill you. All common neurodegenerative conditions are high up on the healthy life extension hit list - we need to have cures or preventions if progress elsewhere in the science of living longer is to benefit us.

Alzheimer's may be a natural consequence of normal ongoing metabolic processes, and we all know by now that neither "natural" nor "normal" necessarily means "good," I trust. Different parts of the brain have different levels of usage, and those areas with greater usage may lapse into Alzheimer's more quickly:

The availability of powerful imaging techniques and the ability to merge different sets of imaging data through new bioinformatics and statistical methods enabled Buckner and his team to construct a picture of Alzheimer's from molecular changes to the structural and functional manifestations of the disease. In the process, the team unexpectedly observed that the regions of the brain that light up when we slip into comfortable patterns of thought are the same as those that, later in life, exhibit the disabling clumps of plaque characteristic of Alzheimer's, a disease that most frequently manifests itself after age 60.

That remarkable correlation, said Buckner, suggests that dementia may be a consequence of the everyday function of the brain.

...

The default state, according to Buckner, is characterized by metabolic activity in specific regions of the brain, notably the posterior and cortical regions. "These regions were active in the default states in young adults and also showed amyloid (plaque) deposition in older adults with Alzheimer's disease," the researchers write in the new Journal of Neuroscience paper.

"The key insight is that brain activity and metabolism are not uniform across the brain," Buckner said. "When we looked at people on the cusp of dementia, we saw a loss of brain tissue in the regions we predicted it would occur," based on our observations of metabolism.

...

Buckner emphasized that the notion of a causative relationship between everyday metabolic functions of the brain and Alzheimer's remains a hypothesis. However, new studies may help "show if amyloid (plaque) deposition is really dependent on metabolism. Can we find a biologically plausible reason for how metabolism causes Alzheimer's disease?"

Food for thought, and possibly groundwork for the second generation of effective therapies. The first generation of effective therapies for Alzheimer's is likely to be based on gene therapy to tailor the immune system into cleaning up the damage - that will work, or so it seems from early stage studies, but prevention is always better than a cure.

The State of Stem Cell Funding
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Ronald Bailey takes a US-focused look at the state of funding for stem cell research in his latest piece for Reason Online. Many proposals for comparatively large-scale state funding programs are under discussion, but very little has actually been accomplished yet, even in those states where the proposals passed. Par for the course in public funding; waste, expensive battles and slow progress. Private and philanthropic funding - always underreported, since finding out about it requires actual work on the part of journalists - is starting to pick up, however, now that the political environment is slightly less openly hostile. "For example, the Starr Foundation is providing $50 million over three years for human embryonic stem-cell research at three New York City medical institutions."

Link: http://www.reason.com/rb/rb082405.shtml

We Will Live Longer
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The Seattle Post-Intelligencer reports on comments from Leroy Hood, founder of the Institute for Systems Biology: "Hood is predicting that technology and medicine will improve within two decades to increase a person's life by 10 to 20 years. ... It takes five years for people to get anything. The first few times they hear it, they can think of a thousand reasons why it's wrong. Then, after they've heard it a few more times, it starts to sound more logical. If you're a missionary, you've got to be patient with your congregation. We are at the very beginning stages of thinking about this. ... You see what drives the change? Technology. If we invent the technologies that enable this, everything else gets dragged right along. That is one of the fundamental rules of civilization. I think it will make medicine less costly, infinitely more efficient. I think within 20 to 25 years, we'll be living productively 10 to 20 years longer."

Link: http://seattlepi.nwsource.com/business/237750_hoodqa24.html

Speculist Posts You Should Read
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I don't link to the Speculist as often as I should - falling down on the job, I'm afraid. So without more ado, here is a selection of recent posts from the Speculist on healthy life extension and related medical advances:

They Went So Young:

Ultimately, it's families, loved ones, and friends who will drive the acceptance of life extension technologies. ... Throughout all the generations of humanity, people have watched their loved ones age and die, and deep down wished they could do something about it. When options are available, people will use them. Of course they will.

Future Healing:

It's 2020. You're a doctor presented with a patient suffering from an advanced, untreated neurodegenerative disease. What do you do? Several recent scientific developments give us some idea.

Covering the Spread:

if radical life extension really will be with us soon, people might want to start thinking about very long term investments. I envision bonds with maturation periods in the centuries.

Good News On Stem Cells:

the notion that stem cells will play a major role in soon-to-come life extension efforts is gaining broad acceptance among researchers ... in order to realize this kind of scenario, we have to make substantial progress in our understanding of and ability to manipulate both adult and embryonic stem cells.

Take the time to read; I think you'll find it rewarding.

Exercise Capacity, Life Expectancy
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The Life Extension Foundation News notes that "One of the best studies to date on why we should exercise was reported in the New England Journal of Medicine on Aug. 4. Yet the terminology and data were so complex that the significance may have gone unnoticed. ... In previous studies, exercise capacity had been shown to be a strong predictor of mortality in women. But this study was even more definitive. Women whose exercise capacity was less than 85 percent of the formula-predicted value were twice as likely to die within eight years. The study offers a powerful reason to pay attention to our own fitness level. A mere 15 percent deficiency can do more than promote weight gain. It can have a profound and serious impact on life expectancy."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2622&Section=AGING

Embryonic Stem Cells To Lung Cells
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ScienceBlog reports on yet another advance in our ability to control stem cell differentiation: "Scientists have successfully converted human embryonic stem cells into lung cells ... This is a very exciting development, and could be a huge step towards being able to build human lungs for transplantation or to repair lungs severely damaged by incurable diseases such as cancer. ... Following further laboratory tests, the researchers plan to use their findings to treat problems such as acute respiratory distress syndrome (ARDS), a condition which causes the lining of the cells to fall off, and which currently kills many intensive care patients. By injecting stem cells that will become lung cells, they hope to be able to repopulate the lung lining."

Link: http://www.scienceblog.com/cms/node/8749

Thoughts on Funding Prevention Versus Repair
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Prevention is cheap, repair is costly. Yet we have a medical establishment that is shackled - by regulation, by its own choice, by other factors - to developing after-the-fact emergency damage repair strategies for age-related disease rather than means of prevention. It is an approach doomed to failure in every way but generating profit - and it won't even be much good at that if socialism and collectivism in the US medical system continue their steady advance. Randall Parker has some thoughts on the matter:

Think of it this way: If potholes in the roads were causing damages to vehicles that far exceeded the cost of fixing the potholes then the political cry would go out to fix the potholes. Well, the cost of diseases and aging - both for expensive treatments and for the costs of disability - run into the trillions of dollars per year. So why do the US National Institutes of Health get less than $30 billion dollars per year while US federal, state, and local governments spend somewhere in the neighborhood of $700 to $800 billion per year for medical care and nursing care? Why does the private sector spend even more while the government also spends money to provide income to old folks who are too aged to work?

While we can not allocate money to repair and rejuvenate bodies as quickly as potholes can get repaired we can allocate money to achieve repairability of human bodies within the lifetimes of most of us.

...

In 2003 health care spending made up 15.3% of the US economy and is projected to rise to 18.4% by 2013 with further increases beyond 2013. Currently US federal biomedical research spending (almost $29 billion out of an almost $11 trillion economy) amounts to less than a third of a percent of GDP. Why spend over 30 dollars delivering care with today's lousy treatments for every dollar spent on research to develop newer, better, and more cost effective treatments? Imagine we spent $30 dollars on car repairs for potholes for every dollar we spent fixing potholes. Our current policies are about that dumb. Effective treatments will be cheaper treatments. Also, effective treatments will boost productivity and economic output by boosting the level of function of the labor force and by allowing people to work more years. Biomedical research will pay back many times over.

I'm not a fan of any sort of government or centrally controlled wealth redistribution, for research or otherwise, but the above suggestion is an iota less terrible than continually funding a failed coping strategy.

This all seems to me like more of the cricket and ant, writ large, tens of millions of people spending vast sums of money in failed attempts to save themselves - often other people's money, through the wonders of coercive wealth transfer - because they failed to invest in medical research for a better future. Because they failed to decentralize the medical establishment, failed to abolish the regulations that increase costs and force most funding and research down less productive paths. Every dollar that is diverted away from healthy life extension research today will lead to many, many dollars in medical costs in the years ahead.

Stem Cell Heart Therapies Spreading
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(From the Cape Times). Trials and studies of first generation stem cell therapies for damaged hearts are spreading. This latest is from South Africa: "A number of South Africans are said to be the first guinea pigs in the medical trial aimed at creating an alternative to the heart transplant. It has been conducted over the past eight months, although it has not yet been peer-reviewed." The patients are reported to have "showed marked improvement over the past few months. Stem cells were reportedly harvested from tissue in the adult patients' thigh muscles, grown in a laboratory and injected into their damaged heart muscles." As always, remember that "one must be careful not to sensationalise research that hasn't been peer-reviewed yet."

Link: http://www.capetimes.co.za/index.php?fSectionId=271&fArticleId=2846116

The Cold, Hard Facts
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The Chicago Tribune looks into cryonics, an experimental set of technologies that remain the only shot at a longer, healthier life - at some future date - for people too old to wait for working healthy life extension medicine: "There are now at least five cryonics facilities in the United States, of which Alcor claims to be the largest. The oldest one, the American Cryonics Society ("Freezing people for more than three decades") was founded in 1969 in Cupertino, Calif. The newest company, Suspended Animation, recently received zoning permission to open a facility in Boynton Beach, Fla., which puts it at the heart of a burgeoning retiree market that presumably has the most urgent need of such services." If you want more details on cryonics, heading over to the Alcor website is a better bet than reading the article - important details have a way of getting lost in translation.

Link: http://www.chicagotribune.com/news/nationworld/chi-0508220106aug22,1,3166363.story

Reprogramming Cells, Yet More Progress
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The Washington Post reports that "scientists for the first time have turned ordinary skin cells into what appear to be embryonic stem cells ... The technique uses laboratory-grown human embryonic stem cells [to] "reprogram" the genes in a person's skin cell, turning that skin cell into an embryonic stem cell itself." Cells are just finite state machines, albeit very complex ones, and a great many doors in medicine open as researchers understand how to manipulate cellular states and programming. This is a promising advance, but is still just a proof of concept; the manipulated cells contain "the DNA of the person who donated the skin cell and also the DNA that was in the initial embryonic stem cell." That extra DNA must be removed, which is a "substantial technical barrier."


Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/08/21/AR2005082101180.html

Beginner's Guide To Searching For Medical Information Online
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You can never have too many beginner's guides; everyone needs one at some point in time. I just noticed an introductory guide to searching for medical information online published at PLoS Medicine earlier this month:

Yet, as many a doctor will point out, the bigger problem with medical knowledge today is not its paucity, but the difficulty of navigating what there is. Finding the right answer quickly for a patient is difficult, and perhaps nothing will replace a good medical librarian in finding that information.

The rise of the search engine Google (www.google.com), along with other freely available search engines, has made it easier to find information, although the clinical uses of Google have not been as well documented as those of PubMed [1]. Google will not point to the answer to every question, and often the articles it finds in response to your question are not freely available. But for many clinical scenarios, Google and other search engines can provide, quickly enough, an answer that is good enough. This article aims to provide tips that will help with these clinical scenarios, saving time that can be used with a medical librarian to answer more difficult problems.

I will be adding this to my list of useful references to point out to those folks who turn up at my virtual doorstep bearing questions.

On Double-Strand Breaks In DNA
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From details of the recent Fanconi anemia research and insight into DNA repair, it is interesting to note that "We have known for decades that patients with Fanconi anemia have chromosomes that break easily ... we can now suggest that DNA double-strand breaks are the lesions that underlie the pathology of this disease." Digging into past material at Fight Aging!, we find "DNA double strand breaks are regarded as one of the primary causes of cancer." If you're of a scientific mindset, you should find the first and second parts of a conversation on aging theories between Robert Bradbury, Aubrey de Grey and Joao Magalhaes to be relevant and interesting: "DNA double strand breaks are bad."

Link: http://www.eurekalert.org/pub_releases/2005-08/nioa-gds081805.php

Shedding Light On DNA Repair
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If we fully understand how our cells repair damaged DNA, then we should be able to find ways to improve on the process in order to prevent age-related degeneration caused by accumulated DNA damage. Here, EurekAlert reports on another step forward towards this understanding: "researchers have discovered a new gene, FANCM, which sheds light on an important pathway involved in the repair of damaged DNA. Specifically, mutation in this gene is responsible for one of the forms of Fanconi anemia (FA) ... understanding this gene's role in the development of FA provides insights into other medical problems - in this case, age-related conditions ... We believe that this new gene, FANCM, may be a potent cog in the DNA repair machinery. It is possible that we could learn how to promote the function of DNA repair complexes and thereby prevent the age-related accumulation of DNA damage."

Link: http://www.eurekalert.org/pub_releases/2005-08/nioa-gds081805.php

Tom Kirkwood Reviews Fantastic Voyage
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My attention was drawn, via John Hawks, to a review of Ray Kurzweil's Fantastic Voyage by aging researcher Tom Kirkwood that is available - for paying subscribers only, sadly - at Nature. To get an idea of Kirkwood's background and thoughts on the matter of healthy life extension, you might want to read one of his recent EMBO Reports papers. John Hawks, who is more the Nature subscriber than I, notes:

The review is basically supportive of the actual content of the books, but at the same time critical of the hype.

...

We know, for example, that, in model organisms, boosting some of the mechanisms for cellular maintenance and repair can indeed extend life-span. This does not mean that the same techniques will necessarily work in humans, because we know from comparative studies that humans are already endowed, for good evolutionary reasons, with much better maintenance systems than shorter-lived species. By analogy, a design modification that boosts the performance of my own modest car will not necessarily make a Maserati go faster, as the Maserati is engineered for peak performance already. But we can try.

I don't think that the current brace of funded work looking at manipulating our metabolic biochemistry for enhanced health and longevity - largely spreading out from research into the mechanisms of calorie restriction - is a bad thing. But it is a different and most likely less fruitful field of science than any form of directly tackling repair and prevention of age-related damage. It's tuning the engine rather than coming up with a better design for longer-lasting components or better tools for repair.

Read Up On SENS This Weekend
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Make some time this weekend to read up on biomedical gerontologist Aubrey de Grey's Strategies for Engineered Negligible Senescence - proposals for a practical approach to developing real anti-aging medicine. If you would like a more gentle introduction, start with the introduction to SENS here at the Longevity Meme, but I think you owe it to yourself to find out more about what the future of healthy life extension could look like. If the science can be discussed in this level of detail, then we are certainly close enough to begin funding research and development - that funding depends on widespread public support. When it comes down to it, we are responsible for building the future we would like to see, and that includes speaking out in favor of real anti-aging medicine and longer, healthier lives.

Link: http://www.sens.org

"...and here is something you can buy."
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As this press release promoting one of the A4M conferences demonstrates, many in the "anti-aging" marketplace are quite hip to the latest science. They read, they stay abreast, they even advocate - the problem is that this is a post-hoc process that always leads to "and here is something you can buy today that will help slow the aging process." This is either a lie or - at the most generous - willful self-delusion. Even calorie restriction is not proven to extend healthy life span in humans - it's just very likely to do so based on the vast weight of evidence to date acquired over decades of scientific inquiry. This weight of evidence is sorely lacking for every product or methology touted by the "anti-aging" marketeers. To prove a slowing (or reversal) of age-related damage we would need either working biomarkers of aging (which we don't have) or wait until people keel over and count the years (which we don't have the luxury of time to do, since we'd be the ones keeling over).

There are plenty of products, techniques and lifestyle choices out there that can fight or help prevent specific - or even multiple or whole classes of - age-related disease. Selling these things for those purposes is in no way unhelpful or unethical. Do any of them "slow the aging process?" What does that phrase even mean in these days of far greater understanding of age-related damage at the genetic and biomolecular level?

Beyond this, all the definitions get nebulous once you start splitting hairs to put together a good marketing campaign based on this "anti-aging" brand. Can you use the Reliability Theory of aging to justify any healthcare or preventative medicine as "anti-aging?" Which averaged-out gains in individual life span count? Fixing heart disease? Better nursing care for the elderly? At some point it all becomes meaningless - especially if your goal is to sell something you happen to have in stock and that cannot be proven effective.

For the consumers reading this: there aren't any silver bullets out there, and you do yourself a disservice by chasing around looking for one. If you want to live a longer, healthier life, then take care of the health basics (exercise, modest supplementation, weight), practice calorie restriction and support medical research into working anti-aging medicine. Especially the latter. It isn't rocket science, it isn't any different from patient advocacy for other medical conditions - we just aren't there yet, and the only we'll see rejuvenation technologies and greatly extended healthy life spans in our lifetime is through advocacy, public support and major research funding.

Is It Harsh To Say The Past Generation Failed?
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Here is an interesting post from the sci.life-extension group, late of usenet and now hosted by Google. The gist of it:

An enourmous problem with the life extension movement is that very little movement is taking place! I have read since the days of Durk Pearson and Sandy Shaw the cliche that we are doubling our knowledge every year and that in a few short years we will be so knowledgable that aging will be a thing of the past.

The reality is that in the almost 20 years that I have been involved in the research and practical application of life-extenstion technologies I have seen very slow progress. With the exception of caloric restriction, we have gained few interventions that might (and that is a painfully truthful word) do us some good.

...

As for the readers of this message, if your in your 20's your have hope, if your in your 40's caloric restriction might save you, if your in you 60's and beyond maybe ALCOR will saw off your head and freeze it if your lucky.

This is not a good situation and one that doesn't speak to the doubling of knowledge to brush aside the simple problem of aging.

This is a view from the old school, yet one that accepts that we are close to working anti-aging medicine and radical life extension by steps and advances - and so a critical question is whether we as individuals can live long enough in good health to benefit. Can we beat the curve with the poor tools we have to hand and what looks to be available in the next few years? These are vital, important questions for all of us - and I don't think we can spend our resources any better than by supporting the future of medical research to the hilt. Chasing solutions in the now - being a cricket rather than an ant - isn't going to build the future we would like to see.

It it harsh to say that the past generation of healthy life extension advocacy movements failed? Could they have achieved greater progress, steered greater investment towards meaningful longevity research? Over the same or shorter periods of time, cancer, AIDS, Alzheimer's and diabetes patient advocates and researchers have built empires - vast and diverse research communities poised and funded to drive technological progress and take advantage of new medical technologies as they become available. Over the same period of time, first generation healthy life extension advocates failed to overcome the very same barriers we face today in our attempts to guide funding towards meaningful anti-aging research.

Why did they fail? Why is it that we have the multi-billion dollar old school supplement industry and the dubious "anti-aging" marketplace rather than a funding network - private, public or both - and responsible, directed research into a cure for aging to match cancer institutes dollar for dollar? What can we learn from the history of our distributed advocacy movement and apply to our efforts in the years ahead?

A New Class Of Stem Cell
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A number of research groups have been working on extracting and using stem cells from the umbilical cord. As Medical News Today reports, scientists are making progress: "They have been using [bioreactors enabling] them to produce stem cells sharing many of the same characteristics as cells found in embryos. Research has so far relied on so-called adult cells found in blood and bone marrow from birth onwards or cells grown from embryos. The new type detected by the team harnesses the benefits of both. 'We have found a unique group of cells that bring together the essential qualities of both types of stem cells for the first time' ... The team has taken its first steps towards proving its claims by growing defined liver tissue using the new cell type."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=29324

More On Fetal Stem Cells
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In light of recent work demonstrating the capacity of fetal stem cells to induce healing, it's worth revisiting some of the other research that has been taking place in this area. From the New Scientist: "Stray stem cells from a growing fetus can colonise the brains of mothers during pregnancy, at least in mice. If the finding is repeated in humans, the medical implications could be profound. Initial results suggest that the fetal cells are summoned to repair damage to the mother's brain. If this is confirmed, it could open up new, safer avenues of treatment for brain damage caused by strokes and Alzheimer's disease, for example. This is a long way off, but there are good reasons for thinking that fetal stem cells could one day act as a bespoke brain repair kit." It may even turn out that we don't need the cells - we just need to replicate the signals they produce.

Link: http://www.newscientist.com/article.ns?id=mg18725134.300

Fetal Stem Cells Promote Regeneration
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First generation stem cell therapies trialed and tested around the world over the past few years - really advances in transplant technology that build on new tools and knowledge - are the results of smart educated guesses and trying things out to see if they work. Progress is being made in understanding how stem cell transplants cause regeneration: if it is in fact the case that transplants work because the transplanted stem cells are issuing biochemical commands to the local environment - a task that existing stem cells fail to carry out due to age-related damage or other problems - then refined versions of these regenerative therapies may proceed without the use of stem cells at all, issuing the necessary signals directly. For the moment we use cells as proxies to accomplish what we cannot; a sign that we don't yet have the knowledge and tools to completely control the inner workings of cells and manage complexity in healing.

Prompting this line of thought is a Nature report on the effectiveness of fetal stem cells in burn regeneration:

Patrick Hohlfeld of the University Hospital in Lausanne, Switzerland, and his team decided to explore the potential of fetal skin cells in grafts. Fetuses have long been known to have remarkable regenerative abilities. Hohlfeld says he expected the skin cells to act as a graft. But the cells seemed to confer restorative powers to the burnt skin, allowing the damaged tissue to heal itself.

The team doesn't know exactly how the skin cells had this effect. But Hohlfeld thinks the technique could work for adult burns, as well as other wounds.

...

Other forms of treating similar burns frequently take up to six times as long. The remarkable flexibility of the skin mended with the fetal cells meant that the patients recovered full movement of their hands and fingers, the authors add.

The result not only gave the patients nearly perfect skin, but also spared them the trauma of having a graft taken from elsewhere on their body, Hohlfeld adds.

As for the present lines of research using adult stem cells, we should expect scientists to make rapid progress towards understanding why this therapy is so effective. Are the fetal stem cells simply manipulating the local environment in a way that transplanted adult stem cells cannot, or are different mechanisms in play? Regardless of the answer, seeking out the mechanisms of regeneration will lead to better answers to all forms of injury and degeneration.

Mitochondrial Decline And Diabetes
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The age-related decline of mitochondria due to an accumulation of mutations in their DNA is thought to be one primary cause of aging. Here, Medical News Today reports on a better understanding of the link between mitochondrial decline and the onset of type 2 (age-related) diabetes: "A detectable decline in energy production by mitochondria - the organelles that are the cell's furnace for energy production - seems to be a key problem leading to insulin resistance, and thus to type 2 diabetes ... a decreased ability to burn sugars and fats efficiently is an early and central part of the diabetes problem. Their new data also suggest the basic defect lies within the mitochondria." Efforts to develop the tools required to repair or replace damaged mitochondria are currently underway.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=29194

Activating Stem Cells For Regeneration?
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SFGate reports on telomerase, stem cells and long-haired mice: "a key component of the enzyme, known as telomerase, can switch on stem cells resting in mouse hair follicles. The otherwise ordinary-looking mice promptly became as shaggy as '70s rock stars. ... In ancient Egypt, men smeared their pates with hippopotamus fat in a desperate bid to stave off baldness. Is telomerase the new hippopotamus fat? Probably not ... Stem cells, found in virtually all organs of the body, are the wellsprings of tissue regeneration. Specialized stem cells in the hair follicles cycle between a quiescent and active state. The timing of these cycles helps to regulate hair growth. In the mouse studies, researchers found that [one component of telomerase known as telomerase reverse transcriptase] 'can kick these resting stem cells into action.'"

Link: http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2005/08/18/STEMCELL.TMP&type=science

Kurzweil's Predictions, Complexity Management and the Future of Healthy Life Extension
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Over at the Longevity Meme, I recently pointed to very good commentary on the implications of Ray Kurzweil's predictions for our life spans - how close are we to agelessness attained through advanced technology? With regard to the varied predictions, economist Arnold Kling seems to be on much the same page as I am; his recent piece at Tech Central Station reminded me of arguments I've made in the dim and distant past on the pace of development. He says:

In comparing the predictions that turned out to be conservative with the predictions that turned out to be optimistic, I detect a clear pattern. Generally speaking, the more open-ended the problem and the more adaptive that the machine needs to be to provide a solution, the less far along we are in arriving at a technological solution. One way to put this is that we can construct tools, but we cannot construct agents.

In other words, progress towards general (and/or strong) artificial intelligence - a grail for many transhumanists and other futurists - has been slower than we'd like. The level of difficulty has been consistently underestimated in the past, and I see this as one part of a larger underestimation of any form of complexity management. You may recall seeing this idea put forward in a variety of 1990s writing on the topic of nanotechnology; the production of millions of nanorobots wasn't thought to be as hard as the process of controlling and managing those nanorobots in a useful fashion - strategies for information processing are as much the key to future medical technologies as nanoscale and molecular manufacturing. Complexity is hard, both to manage and estimate in advance.

Now replace "nanorobot" with "human cell" and that's where we are today with biotechnology. Biological systems - such as your body, or even just a small piece of it - are immensely complex. The reason researchers can make meaningful progress today with medical technology such as gene therapies and stem cell research is that they are, effectively, tweaking settings on existing machinery that largely handles the complexity management itself. Our grasp of how things work - based on our ability to process information and build the tools required to gather information and effect change - is now adequate for this task, just as it is almost adequate to guide existing biological machinery to build replacement tissue and organs in a useful, controlled manner. But it seems to me to be a very large leap - in terms of managing complexity - to go from where we are today to reach the point of, for example, replacing biochemically complex systems within the body with artificial substitutes. Or reverse-engineering the brain, that sort of thing.

People are working on making this future a reality, the technologies of information processing are advancing by leap and bound, and science will get there eventually. The bigger question to my mind - being a first things first sort of person - is whether the first generation and intermediary technologies of healthy life extension, each better than the last, prove to be effective stepping stones. Will early SENS or regenerative medicine therapies enable us to live healthily for long enough to see a Kurzweilesque tomorrow? Or live healthily for long enough to to use the next, nore effective therapy that will take us into Kurzweil territory? Will these working anti-aging medical technologies be developed at all? That is, as I have often said, up to us.

Looking More Closely At Sirt1
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Scientists are making progress in understanding connections between the Sirt1 protein, metabolic regulation and life span: "Sirt1 is referred to as Sir2 in lower organisms where it has previously proven to be a key to aging and longevity: Increasing the amount of Sir2 dramatically extends life spans in experimental yeast, worms and flies. ... In mammals, scientists have shown that restricting calories can extend life span and also leads to an increase in Sirt1, the mammalian version of Sir2. ... Sirt1 is probably a very important regulator that integrates cellular response to different types of nutrients, such as glucose, amino acids, and fatty acids." We can hope that a full understanding of the mechanisms of calorie restriction will lead to therapies that can improve on gains in healthy life span obtained via this method.

Link: http://mednews.wustl.edu/news/page/normal/5577.html

Another New Aging Gene
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EurekAlert reports on another gene newly connected to the aging process: "Researchers have discovered that the loss of a gene called p63 accelerates aging in mice. ... Aging and cancer are two sides of the same coin. In one case, cells stop dividing and in the other, they can't stop dividing. We suspect that having the right amount of the p63 protein in the right cells at the right time creates a balance that enables organisms to live relatively cancer-free for a reasonably long time." A lack of p63 accelerates aging in tissue - but then so do a large number of other things. There's no such thing as useless information in the biochemistry and genetics of aging, but it remains to be seen how important this new discovery turns out to be.

Link: http://www.eurekalert.org/pub_releases/2005-08/cshl-gla081505.php

More Use It Or Lose It
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While I was in the "use it or lose it" frame of mind, the latest SAGE Crossroads article caught my eye:

The age-related atrophy of muscle tissue originates within muscle cells themselves. The bundles of contractile fibers that give muscles their stretch begin to vanish. And the fibers that remain start to shrivel and don't produce the power they did in their youth.

But what drives this decline remains a matter of some debate. Biochemist Ewa Prochniewicz of the University of Minnesota, Minneapolis, pins part of the blame on accumulated damage to actin and myosin, the proteins that drive muscle contraction.

...

Another theory for why muscles fizzle with age builds on the "use it or lose it" hypothesis. Muscles contract only after they've received the go-ahead from embedded nerves - nerves that don't fire as vigorously in older adults. Thus, aging muscles receive fewer nerve signals and eventually die from disuse.

Another interesting passage:

But injured muscles can repair themselves by building new fibers, at least in younger people, and some scientists are testing whether aging muscles weaken because they lose this regenerative capacity. Neurogerontologists Jan-Erik Edstrom and Brun Ulfhake of the Karolinska Institute in Stockholm, Sweden, categorized a group of aging rats as either "well-preserved" or "severely affected" based on their performance on standard tests of strength and balance. Surprisingly, they found that the leg muscles from the gimpier rats appeared to have tried harder to mend themselves: They contained larger quantities of proteins that jump-start muscle development than did the better preserved muscles. Why muscles poop out in spite of their apparent potential for restoration remains unclear, Edstrom says.

It is possible that this has something to do with the age-related decline of muscle stem cells; you may recall recent work showing that these aged stem cells can be jolted back into operation with the right biochemical cues, giving old muscle a youthful capacity for regeneration. Given that age-related decline in strength and muscle capacity is a downward spiral - the more you lose, the less able you are to slow further losses with exercise - this sort of research can only be a good thing.

While scientists are pinning down causes, I don't see anybody arguing that exercise is a bad thing or that it doesn't help to slow age-related degeneration. Given the choice between full-speed or slower degeneration while we wait for medical technologies capable of repairing age-related damage, I think I know which option I'll be taking. Here is a final thought from the article:

There's no one drug that could purport to have all the behavioral, psychosocial, and physiological effects of exercise and physical activity.

Yet. But exercise while you're daydreaming about not having to. It'd be a shame to miss out on the benefits of future medical technology because you let things slide today.

A Reminder About Fat
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The PakTribune reports that researchers "found that the more people weigh, the older their cells appear on a molecular level, with obesity adding the equivalent of nearly nine years of age to a person's body. The findings suggest that many health problems associated with being overweight - heart disease, cancer, diabetes, arthritis - may result from fat cells hastening the natural aging process." Correlation is not causation, but "the results are consistent with recent findings that, contrary to the long-held belief that fat cells are inert blobs, they churn out a host of substances that can be toxic to the body ... So it may be the body has to repair itself much faster and that accelerates the aging process." Poor diet and lack of exercise that accompany obesity could also be to blame - it's clearly a good idea to maintain a healthy lifestyle and keep the weight off.


Link: http://paktribune.com/news/index.php?id=115782

Nerve Stem Cells Made
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The BBC reports on progress in control of embryonic stem cell differentiation: "The world's first pure nerve stem cells made from human embryonic stem cells have been created ... "This is incredibly exciting in terms of curing disease. We may be able to create the disease in a dish. If we do that, we'll be able to better understand the disease and also to test drugs. ... the long-term aim of the Edinburgh research is for cells to be used to build replacement neural tissue for Alzheimer's and Parkinson's sufferers. But he said the more immediate use for the artificially-created cells is to test out the effectiveness of new drugs. ... Hopefully that will come to pass within two to three years. In terms of the possibility of using the cells for transplantation, that's a much more difficult and longer term thing and I think there we're talking more of the five to ten year range."

Link: http://news.bbc.co.uk/2/hi/science/nature/4155016.stm

It's a Strange Old World
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I've recently been exploring Alexa's traffic rankings once more after a long hiatus. It seems odd, to me at least, that both SAGE Crossroads (754,181) and InfoAging (565,333) trail the Longevity Meme (346,233) and Fight Aging! (246,681) by a fair amount. Both are good resources, and I would have expected them to see more use, even though they don't go in for daily updates. Still, this would seem to be the upside-down world we see online these days; reference sites get little traffic, while sites that reference get much more. The Longevity Meme tries to be both, but it's clear from the logs that people come for the buffet rather than the library. The library is a large part of the purpose for which the Longevity Meme was built - but if the popularity of the buffet leads more people to find the library next door, then all is well in the world.

The "also visit" lists on the Alexa pages linked above are interesting in and of themselves, implying that there isn't a great deal of overlap between Fight Aging! readers and Longevity Meme readers. Or maybe there is - it's hard to tell when the silent majority remains silent. One of the great joys of running any sort of website is that you live in a sea of reporting and content, but truly have no clue as to what is actually going on.

On a related, happy note, the Mprize for longevity research (645,985) is currently where the Longevity Meme was a year ago or so - and may that growth in visitors continue. The more people who are exposed to the Mprize message, the better: degenerative aging could be cured in our lifetimes, and here is a way, today, for you to help and encourage the necessary research.

How Adult Stem Cell Therapies Work
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An adult stem cell therapy for acute renal failure (ARF) provides insight into how these first generation therapies work. EurekAlert reports that transplanted stem cells are only present briefly, but administer a swift, positive kick to the local environment: "Administered stem cells don't stay in the kidney that has ARF long enough to differentiate into kidney cells, but rather appear to alter the course of ARF by a number of identifiable and some still unexplored paracrine mechanisms. The former include the induction of organ-protective and repair-supporting genes in surviving renal cells, robust suppression of proinflammatory cytokines in the ARF kidney and upregulation of anti-inflammatory genes, as well as the delivery and release at the site of injury of organ-protective and other beneficial gene products by the stem cells."

Link: http://www.eurekalert.org/pub_releases/2005-08/aps-scb081105.php

A Path To Technological Immortality
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A Tech Central Station author provides a good overview of the prospects for forms of physical immortality in 2050 that have much more to do with nanotechnology and computational science than with medical biotechnology - a merging of man and his machines that produces immortality almost as a side-effect along the way to far greater things. Good, well-studied predictions of the technological singularity to come have at least a decade-long history, and it is hard to argue against the fact that progress in core convergent technologies and sciences is accelerating rapidly. Still, for most of us, standard old-fashioned human-sourced hard work on first-generation healthy life extension medicines will be needed if we are to be healthy and alive in 2050. First things first.

Link: http://www.techcentralstation.com/081505C.html

"Use It Or Lose It" For The Brain
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(From the Washington Post). Here is another of my infequent reminders about exercise - a vital part of maintaining good health so as to live long enough to benefit from future medical technologies. This applies just as much to the brain as the body; if you don't make use of its varied capabilities, the brain will degenerate more rapidly across your life span. "Some people might have brain networks that are more efficient and so have a greater capacity to compensate for disease ... You have to be cautious. We don't want to create false hopes that you can prevent Alzheimer's ... One of the most striking findings was how it affected function in the area of the brain that creates everyday working memory. We may not have conclusive proof. But the evidence is strong. And these are all healthy choices for other reasons."

Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/08/13/AR2005081300855.html

Revisiting Fiscal Nonsense
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As Kevin Perrot recently pointed out, any suggestions that longer, healthier lives for all would somehow lead to financial problems are an indication that present day government-imposed wealth transfer systems (such as for healthcare and social security) are wrong-headed and broken - and always were. The Mature Market here presents another report that looks at the unfolding regulatory situation in the context of ever-lengthening healthy life spans. While you read, think about the basics - if you are active and healthy for more years, you can work and save for more years. You can change careers to keep things interesting. Retirement will fade to be replaced with very lengthy holidays for those who want a rest between vocations. Above all, you'll be alive and healthy to enjoy life! How could this not be an improvement?

Link: http://www.thematuremarket.co.uk/uk/dossier.php?numtxt=5302&idrb=7

The Purpose of Conferences?
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Jordan Ginsberg wasn't overly impressed with the recent World Transhumanist Association (WTA) conference:

The best way I can think of to describe this year's TransVision conference is likening it to a tattoo convention where the only things on display are bottles of ink, needles, and transparent paper. Technically, yes, those are some of the base elements involved in the craft - but on their own, they tell you absolutely nothing about the subject. More than that, even for beginners, they're a useless starting point.

What is the purpose of conferences for distributed, loosely organized advocacy groups - be they futurist, healthy life extension, or other? Clearly only a fraction of those associated with the group attend, and even the phrase "associated with the group" describes a continuum of shades of involvement and sympathy. Pro-technology futurists, like transhumanists and healthy life extension advocates - or actual scientists performing actual work - are largely self-organizing. Conferences are a high-profile manifestation of this process of organization, just as they always have been. Whether conferences are aimed at deepening the shade of involvement of periphery associates, cementing ties between core activists and advocates, recruiting the uninvolved, or even necessary at all is largely a function of the group involved. I'm not sure what the intended purpose of the WTA conference was, but Ginsberg was expecting something different.

Transhumanism has bled into the mainstream in any number of ways over the past two decades, in much the same way as the culture of science fiction, but has somehow managed to retain true minority status. To a certain degree, I believe this is because founding transhumanist advocates and thinkers of the present day movement have already succeeded in their goals. Ideas - such as radical life extension - that were once firmly fringe are now seriously discussed and considered far and wide. People have picked up the ball and are running with it. More traditional means of advocacy, education and funding to make the future real are now the name of the game, and developing the technologies of healthy life extension has become no different in practice than working to cure disease.

The 21st century is here - all change, all the time. But we wouldn't be in this presently favorable position for the future of healthy life extension without the advocacy of transhumanist groups over the past few decades.

Aubrey de Grey at the Eris Society 2005 Meeting
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It seems worth noting that biomedical gerontologist Aubrey de Grey recently gave a well-received presentation at the 2005 meeting of the Eris Society. For those not in the know, these get-togethers can best be described as a social meet and greet for a certain type of A-list person; libertarians, pro-science futurists, healthy life extension advocates, and representatives from some of the odd, strange and wonderful subcultures that prosper in the gaps in between. Donations to the Mprize for longevity research and a few new memberships of The Three Hundred were forthcoming from attendees who strongly agreed that the time - and state of biomedical science - is right for directed research into a cure for aging. Welcome aboard!

Xenotransplantation, Neurodegeneration
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The field of xenotransplantation has been somewhat eclipsed in the popular view by the advance of stem cell based regenerative medicine, but work continues - such as that reported here by the New Scientist. "Pig brain cells could be implanted into human brains by the start of next year if trials of a pioneering treatment for Huntington's disease are approved in the US. Similar tests on primates have proved 'astonishingly successful' in treating the degenerative brain disease." The pig cells do not replace human neurons; instead they repair damage to the cellular environment caused by progressive neurodegeneration. Huntington's is not an age-related condition per se, but this general strategy looks promising for other, much more common neurodegenerative diseases.


Link: http://www.newscientist.com/article.ns?id=mg18725124.400

Why Naked Mole-Rat Longevity?
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Naked mole-rats (NMRs) pose a opportunity for study in the field of aging science. Why do they live eight times longer than similarly-sized rodents? For that matter, what are the mechanisms whereby some other species of animal manage to live far longer than their peers? In the case of mole-rats, it appears not to be related to antioxidants and the free radical theory of aging: "The present study tested if NMRs possess superior antioxidant defenses compared to mice and if age-related interspecies changes in antioxidants were evident. ... It is nonetheless unlikely that antioxidant defenses are responsible for the eight-fold longevity difference between these two species. Maintenance of constant antioxidant defenses with age in NMRs concurs with previous physiological data, suggesting delayed aging in this species."

Link: http://dx.doi.org/10.1016/j.mad.2005.06.009

Tissue Engineering Progress Continues
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The recent venture funding for Tengion would seem to be why Dr. Anthony Atala's work on tissue engineering is getting press placement of late. Such is the way the world works, but it doesn't make the level of scientific progress any less interesting: "Atala said his research with engineering organs is still at the preclinical stage, which means it has not been tested in humans. However, when he transplanted these artificial bladders into dogs that lacked functional bladders, the organs developed and functioned normally after a month. Atala has helped develop [urethras] which have successfully been implanted in humans. He has created blood vessels, muscle, wombs and vaginas, which have been successfully tested in animals and are close to being ready to test in humans."

Link: http://www.knoxstudio.com/shns/story.cfm?pk=ORGANS-RECIPE-08-12-05&cat=AN

Reprogramming Stem Cells
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(From MSNBC). Stem cell research will lead - we hope - to a complete understanding of cellular machinery, an essential first step towards all the most futuristic visions of medical science. The mechanisms of differentiation are a good early target in this research: "Imagine being able to reprogram the cells of your own body to produce fresh heart cells, regenerated nerve cells to heal spinal cord injuries, pancreatic cells to stop diabetes - or any other type of tissue to cure what ails you. ... Our group, and I know at least two or three others, are playing with different techniques, and it's very clear that something is going on here. We're definitely getting reprogramming." Sadly, anti-research groups use this sort of news to try and denigrate embryonic stem cell research, a field that is vital to achieving near- and long-term research goals in the fight to cure age-related illness.

Link: http://www.msnbc.msn.com/id/8805408/

Stem Cells Essential to Rejuvenation and Healthy Life Extension
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You'll find some good commentary on recent EMBO Reports research papers ("Youthful prospects for human stem-cell therapy" and "Stem cells and aging") from Randall Parker over at FuturePundit. Go and read it all, but here are some highlights:

The problem with stem cells in older bodies does not appear to be so much diminished numbers as diminished abilities in those stem cells which remain.

...

As we age we all would benefit from infusions of youthful stem cells carefully selected to have few DNA mutations. We'd gain stronger immune systems, less risk of anemia, and probably stronger bones as well. More generally, the development of genetically sound and youthful stem cells for all the stem cell reservoirs of the body would partially reverse aging and substantially increase life expectancies.

It may just be that the results of stem cell science over the next twenty years will give us more than a few extra years of healthy life to wait out the development of the other necessary components of Aubrey de Grey's Strategies for Engineered Negligible Senescence.

The Growing Mprize For Longevity Research
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Jay Fox notes that the total of cash and pledges for the Mprize for longevity research is growing rapidly thanks to many generous donors: "At the current rate of growth, the Mprize should easily reach two million dollars by year's end. But let's not settle for that. Let's continue to advocate and advertise, and try to help accelerate the growth of the Mprize fund, and hence accelerate the power the prize has to inspire research, or even to create controversy and publicity, which can be leveraged to raise further funding and inspire research. Let's help accelerate the intentional search for the cure for aging, and help save hundreds of millions of lives, perhaps billions of lives." If you support the future of healthy life extension, then make a pledge to the Mprize, or better still join the ranks of the 300!

Link: http://www.longevityfirst.org/archives/2005/08/mprize_breaks_1.html

Revitalizing The Immune System
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EurekAlert reports on positive early results in efforts to repair aging and failing immune systems. Researchers "have revitalised the thymus which produces the T cells required to fight infection ... the immune system deteriorated severely with age, and was further destroyed by severe viral infection and common cancer treatments ... inhibiting sex steroids improved the production of haemopoietic stem cells in bone marrow. These cells provide 'fuel' for the bone marrow and thymus to produce blood cells. ... Because the scientists have been able to manipulate the way the thymus grows back, they believe they should be able to rebuild the immune system of patients who are receiving [organ and stem cell] transplants so donor material is not rejected."


Link: http://www.eurekalert.org/pub_releases/2005-08/ra-isd080905.php

Two Entry Points to the Sad Second Path
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Following on from yesterday's post, I see two main entry points to the sad second path for the future of healthy life extension - the path that sees us all suffering and dying from age-related degeneration because the technologies to save us from this fate arrive too late.

The first: that the distributed global advocacy community for longevity and life-extending research never attains critical mass, never manages to sufficiently educate the public to tell the difference between junk science and real anti-aging research, never starts the research funding avalanche. Our models for success are AIDS advocacy since the 80s, or patient advocacy for cancer across the past three decades. It's up to us to make this movement just as successful - all our lives are at stake.

The second entry point to a future in which medicines capable of extending our healthy life spans arrive too late is one in which the monsters of regulation, nationalization and socialism in medicine (and no end to socialism in medicine, sadly) impede research and progress. Government investment is, by its very nature, enormously inefficient when it comes to producing results. Demonstrably so - the incentive structure is counterproductive, as decision makers have no meaningful reward for success nor penalty for failure. Even worse is government investment coupled with protectionism, making it the only game in town. Competition is the alchemy by which selfish human nature produces greater good - just look at what happened to the space program in government-enforced absence of any meaningful competition. Billions upon billions spent for very little gain; there is nothing to say that this couldn't happen to medicine in these times of ever bigger government and ever greater attempted social control. The worst case scenario would be for the present trends in socialism in medicine in the US and Europe to continue and spread in Asia as well; it would cripple the research communities and our chances of longer, healthier lives.

Two Paths to the Future
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There are two paths to the future of healthy life extension. In the first path, the technologies we can see clearly ahead of us today are heralded, funded, developed and deployed - the seven modes of aging damage are either validated or extended as a good model for the defeat of aging, and repair and prevention strategies are created for all of them. We'll be able to look back to this time of hectic biotechnological development, and forward to a future that is as long as we care to make it.

The second path is one in which future development of working healthy life extension technologies is assumed but not acclaimed, is treated with only moderate interest, is mismanaged or centralized under government control. If this happens, we'll only be able to look back on what could have been, for we won't have a future - our time will have run out.

For an example of the first path in action, look back at the past thirty years of history of the computer industry, enabler of modern bioinformatics. For the second path, look no further than the past thirty years of the space industry or deep sea exploration. The future is not a given - just because something is possible is no guarantee that it will happen. The difference between the first path and the second path in technological development is in our hands.

DNA Repair Mechanisms And Longevity
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Here is a worthwhile article from The Scientist earlier this month. "Understanding the mechanisms that underlie aging remains a bedeviling problem, but not because of a lack of answers. If anything, there seem to be too many answers - or at least enticing clues - each leading in different directions. Thus, researchers are bound to get excited when a single molecule appears to play roles in several perceived longevity pathways, raising hopes that one could weave a coherent theory. Several strands of evidence have linked PolyADP-ribose polymerase-1 (PARP-1) to potential aging-associated processes such as DNA-repair, telomere maintenance, and apoptosis. But many still question PARP's role in longevity." For a good introduction to one small part of the aging puzzle, read on.

Link: http://www.the-scientist.com/2005/8/1/22/1

Aiming At Cells Made To Order
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The latest SAGE Crossroads article takes a broad look at the aims of stem cell research and regenerative medicine, with a focus on the work of Woo Suk Hwang's group. "They and their colleagues generated the world's first customized human embryonic stem (ES) cell lines, each line tailored to genetically match one of nine patients who suffer from a variety of maladies, including spinal cord injury, diabetes, and an inherited blood disorder. ES cells are believed to be pluripotent, able to develop into any cell type in the body. Thus, they could potentially supply spare parts: lab-grown tissues that would repair ailing hearts, spinal cords, or even brains. And using genetically matched cells like the ones Hwang and Moon produced could keep patients from rejecting such transplants."

Link: http://www.sagecrossroads.net/Default.aspx?TabID=28&newsType=ArticleView&articleId=127

The Best Embryonic Stem Cell Research
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(From EurekAlert). Promising signs of a movement of funds into what I consider to be the best of present day embryonic stem cell research - work aimed at uncovering the biochemical and genetic mechanisms of these cells. "If we are to realize the tremendous potential of stem cells, we urgently need more fundamental knowledge about their basic biology and more scientists trained to work with them. ... Each center will establish a core facility to support and train scientists and to define the growth conditions and molecular characteristics required for maintaining human embryonic stem cells in an undifferentiated state. Scientists at the centers also will work on specific pilot projects to advance fundamental knowledge of human embryonic stem cell properties and functions." This sort of work is key to more rapid advances in regenerative medicine.

Link: http://www.eurekalert.org/pub_releases/2005-08/niog-nfn080905.php

Gene Expression and Brain Rejuvenation
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We should all be rightly concerned about the future of brain rejuvenation - whatever the technologies used, repairing (or even identifying and understanding) age-related damage to the brain looks to be a lot harder than anything else we have on our plate. It's also a great deal more crucial. After all, the worst case scenario for, say, a liver or heart is that we hook it out and replace it with a new one grown from our own tissue. That won't be science fiction a decade from now, and nor will more subtle methods of dealing with age-damaged organs using stem cell based regenerative medicine. We may even solve the problem of growing new organs from our aged cells that are youthful in aspect within the next decade or two - undamaged mitochondria, long telomeres, repaired DNA. But we are our brains, and the brain is a good deal more complex than the rest of the body - so the hardest repair job is also the one that has to be done in situ with no wholesale replacement of parts.

Randall Parker discussed these issues in connection with a recent study of changing gene expression in the brain with age. It's well worth reading:

I see the brain as by far the toughest challenge for the development of rejuvenation therapies. For many parts of the body the simplest approach to rejuvenation will be parts replacement. Once tissue engineering and stem cell research advance far enough we'll be able to replace bad parts just as mechanics do with old cars. Got old failing kidneys dodgy lungs ruined by emphysema? Grow new ones. Is your liver shot? If you don't want to get a whole new liver then send in stem cells that programmed to gradually replace the existing cells with new ones. Got liver scar tissue that doesn't want to go away? Send in cells programmed to eat it up to make room for new liver cells made from stem cells. But the brain's three dimensional network of neural connections defines who you are. Put a new brain in place of your own and that body will no longer be you for most practical purposes.

To rejuvenate the brain each cell in the brain must be repaired. But the scope of such a repair job is enormous. While estimates on the number of neurons in a human brain vary the range goes from 10 billion to 100 billion or 100 billion to 200 billion with the number of neuroglial support cells ranging from 5 to 10 times the number of neurons or perhaps 50 to 100 time sthe number of neurons. So we might have a half trillion or even a trillion cells in our brains, all aging and accumulating DNA mutations, intracellular lysosomal junk, and other damage. To develop methods repair all those cells right in the brain is an enormous scientific and engineering challenge.

While stem cell therapy gets a great deal of press (and deservedly so) and while stem cell therapy does have a crucial role to play in brain rejuvenation stem cells can not do most of the brain repair job. Much of brain rejuvenation probably requires highly advanced gene therapy delivery methods and basically DNA programs to send into cells to carry out repair tasks. Future advances in nanotechnology will eventually produce nanobots that can carry out many brain repair tasks. But to repair DNA we need gene therapy to send in corrective sequences to replace mutated sequences and deleted sequences.

If you treasure your ability to think and your mental identity then support a rapid increase in the rate of development of gene therapies and other therapies aimed at brain rejuvenation.

It's a big task - recall that Paul Allen is putting a hundred million dollars into simply understanding the genetics of the brain. That's a start, but it is only a start. There is much more to come.

On Investing In Healthy Life Extension
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Wired concludes that investing in healthy life extension ventures is much like investing in the rest of biotechnology - a risky proposition. "Plowing cash into companies pursuing remedies for the ravages of age isn't the safest prescription for investors' financial well being. Biotechnology, the industry that promises the broadest potential for life-extending breakthroughs, is a notoriously risky investment play ... Still, investors [have time] to be patient. If it all works out, and we really do live forever, that should provide plenty of time for a portfolio of biotechnology stocks to turn a profit." It seems to me that biotech stocks over the past decade or so look much like early computer industry stocks - all very much a roll of the dice. It stopped being that way, you may recall, as the industry matured.

Link: http://www.wired.com/news/print/0,1294,68073,00.html

Relying on the Wider Community to Keep Me on the Straight and Narrow
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It has to be said that, despite a scientific background and four years of increasingly closely watching aging research news, I'm seeing an upturn in items in the past year that I just can't clearly call as useful or useless, excellent progress or utter nonsense. I'm fairly sure that I've managed to refrain from posting links to anything outrightly silly or useless - and hopefully from writing anything outrightly silly or useless - but it does bring home that it takes a community to process what's going on in modern bioscience. It's up to you lot to keep me on the straight and narrow, so keep the comments coming.

For that matter, this sort of experience underscores the need for gentle introductions to various topics within the realm of healthy life extension and related medical research. Drop a library on a man and you won't have an advocate or enthusiastic community member - you'll have someone flattened under a library. The workable approach is to provide a good introductory book, the catalogue and key to the reading room and let the recipient take it from there.

More On Worms, Telomeres And Aging
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ScienceDaily has a better piece on recent research into telomere length and aging in nematode worms: "For successful aging you have to control both, aging in your dividing cells, which hinges on telomere maintenance, but also aging in your non-dividing cells. We thought that telomeres might play a role in the latter but that's clearly not the case. What is probably playing a role in the other half of aging is the insulin signaling pathway, proper mitochondrial function and dietary restriction ... To prevent accelerated aging in an organism, you need to have both proper telomere maintenance and those other genetic pathways intact. If you wanted to develop a drug to combat aging it wouldn't be enough to target telomeres, you would also have to target these other genetic pathways."

Link: http://www.sciencedaily.com/releases/2005/08/050805175722.htm

Hows And Whys Of Brain Aging
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Betterhumans reports on one small step forward in understanding how the capabilities of the human brain decline with age: "Aging brains have been found to produce diminished amounts of critical growth factors that spur the birth of new neurons in the brain's learning and memory center. ... We determined that there is no major, fundamental defect in how newly born cells behave in the aging hippocampus. There is simply less of the growth factors that drive stem cells to produce new neurons. This is encouraging news because it means we can employ strategies to increase the levels of these growth factors and see whether an increased production of new neurons can be sustained in the aging hippocampus." So comparatively simple medical technologies may be able to repair age-related decline in learning and memory abilities.

Link: http://www.betterhumans.com/News/1064/Default.aspx

Search Terms Prompt Thought About the Cricket and the Ant
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If you had access to the Fight Aging! application log, you'd see - in between reams of blocked spam comments - a vast array of commonplace search terms from the loud, nonsense-infested "anti-aging" marketplace. All sorts of supplements and hormones, this, that and the other; if it doesn't work and someone, somewhere is trying to sell it as a way to retain some aspect of your youth ... there it is, in the Fight Aging! search log of requests entered by folk passing through or doing their research online.

Part of the reason that Fight Aging! and the Longevity Meme exist is to try to educate the folks perfoming these sorts of searches, to show them that they are expending their energy in the wrong direction. We are close to real, working anti-aging medicine, after all - with the right level of public support and investment in research. It all brings to mind nothing quite so much as the fable of the lazy cricket and the industrious ant - although this may be somewhat unfair on the crickets in this case. My point is this: if you find yourself playing the role of the cricket, looking for necessities at the last minute in any aspect of life, then you are likely out of luck. Nothing in this world happens without preparation, hard work and a sound recognition of what the future will bring. The winter of age-related degeneration approaches for us all - indeed, we have a very good idea as to when it will arrive. We cannot wait until aging hurts and incapacitates us to search for medicines that will repair the damage to our bodies and enable us to live longer, healthier, active lives. If we wait, if we laze rather than work to ensure that the right research is funded, then it will be too late in the decades ahead. We will suffer, become crippled, and die.

Do you save for your retirement? I'm sure you do if you're of working age. If you can look that far ahead for financial matters, why are you not also investing a similar level of resouces to ensure that you will not be crippled by age-related diseases? Be an ant. Don't be a cricket.

The State Of Stem Cell Heart Therapies
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From Voice of America, an look into the current state of first generation adult stem cell therapies for heart disease: "Three months after the injections, more than 100 patients saw significant improvement in blood flow to the heart and the heart muscle worked twice as well as before the treatment. ... You can see where the blood vessel is blocked. You can see the blood flowing and then it just stops. Now, three months later, after injection of stem cells in that area, you can see that there's a new vessel bringing the blood down. ... Researchers say when it comes to building blood vessels, using your own cells could become a common treatment within a few years - very good news for the millions of people who suffer from heart disease."

Link: http://www.voanews.com/english/2005-08-04-voa43.cfm

More From The Aging-Cancer Overlap
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There is a great deal of overlap between research into aging and cancer; both result from the same mechanisms of cellular life span. The BBC reports on the relationship between cellular senescence and certain cancers: senescence, "which is part of aging and is controlled by certain genes, results in cells - and tumours - failing to respond to normal growth signals. Men with prostate cancer lack the genes that appear to mediate this process ... [a study] in mice suggests correcting this could be a way to prevent prostate tumour growth." In the recent past, another group "found senescence kept human moles in a non-cancerous state for year, and without it they could develop into a dangerous form of skin cancer called malignant melanomas in the lab. Similarly, a team from Germany showed that cellular senescence is capable of blocking a cancer called lymphoma in mice."


Link: http://news.bbc.co.uk/1/hi/health/4729447.stm

How Much Of A Difference In Life Span?
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This LEF News reprint isn't new news, but I wanted to point it out as a reminder of the difference we can make to our healthy life spans using only the simplest of methods available today - exercise and diet. Radical life extension and working anti-aging medicine have not yet arrived, but we have a fair amount of control over whether we live to see them. "A recent study conducted by UF found that mutations in the energy center, or the mitochondria, of a cell were caused by obesity and lack of exercise, he said. These mutations can lead to apoptosis, or programmed cell death, and may be directly related to the aging process. ... People don't respect food, they abuse it. Fifty percent of the U.S. is killing themselves by not being physically active and having a poor diet. ... By respecting your life and respecting your body, you could add 30 years to your life span. It's that simple."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2534&Section=AGING

Telomeres, Longevity, Not So Simple
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Betterhumans reports on a recent PLoS Genetics paper: "Researchers are claiming to have found 'conclusive evidence' that the link between longevity and chromosome caps called telomeres is more complicated than thought. ... researchers have shown that the worms can succumb to old age despite having long telomeres and can move youthfully despite having short telomeres. ... Some long-lived species like humans have telomeres that are much shorter than the telomeres in species like mice, which live only a few years. Nobody yet knows why. But now we have conclusive evidence that telomeres alone do not dictate aging and lifespan." Nonetheless, there is a certain weight of science behind the correlation between shortened telomeres and age-related degeneration.

Link: http://www.betterhumans.com/News/1062/Default.aspx

Recent Posts You Should Read
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As the title suggests, here are some recent posts from elsewhere in the blogosphere that you should read during your stroll about the net today:

FuturePundit - New Tool Speeds Up DNA Sequencing By 100 Times:

Biotechnology is going to advance at the rate of computer technology because biotechnology is shifting toward the use of very small scale devices. The current cost of human DNA sequencing is in the tens of millions of dollars per person. But that high cost won't last for much longer.

...

The researchers see their techology following a similar pattern to the development of integrated circuits which have sped up at the rate predicted by Intel co-founder Gordon Moore with his famous Moore's Law.

FuturePundit - Harvard Group Lowers DNA Sequencing Cost Order Of Magnitude:

The commercial DNA decoding technology they are referring to is from 454 Life Sciences Corporation and you can read about it in my post "New Tool Speeds Up DNA Sequencing By 100 Times". Whether the Harvard or 454 Life Sciences approach can go further in lowering DNA sequencing costs in the long run remains to be seen. But these are not the only two efforts aimed at lowering DNA sequencing costs and another company or academic group might yet bypass both of them.

FuturePundit - Average Age Of Cells In Body May Be Below 10 Years:

Note that the vast majority of neurons have existed since childhood. The need to rejuvenate existing neural cells makes brain rejuvenation by far the hardest part of the total rejuvenation therapy development puzzle. While the researchers found that in some parts of the brain the average cell age was less than the age of the person in the visual cortex the brain was about the same age as the person.

...

The fact that on-going cellular division makes most cells chronologically young and that old cells divide less well actually presents an opportunity for the development of rejuvenation therapies. The development of technologies for producing youthful adult stem cells will provide sources of youthful and healthier stem cells cells to replace the older and less healthy cells that accumulate in our bodies as we age. Since older stem cells divide more slowly rejuvenated stem cells introduced into various parts of the body would out-compete and gradually displace the older cells.

Classical Values - Maybe this time, denial can be made to work:

It's frustrating to see that there's really no available life extension technique which actually works now, though.

...

Ray Kurzweil speaks of a 15 year wait, and says that if we can stay alive for fifteen years, there's a real chance of workable, real, life extension.

Might it just be true?

This time?

The fact is, despite my talk of replaying 1980s denial, at the time of all the useless remedies and experimental drugs, genuine workable AIDS treatments were only fifteen years away.

The advancing technology of the 21st century is very impressive; it's clear that we're moving into new and different territory in the arena of biotechnology, changes spurred by dramatic improvements in efficiencies and capabilities of the tools of the trade. We should not forget why we are doing this, however, why we support medical research into aging, age-related disease and longevity - it's to save the lives of billions who will otherwise suffer and die in the years ahead.

Neurodegeneration And Quinolinic Acid
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(From Medical News Today). Interesting news from Alzheimer's researchers: "We found that all of the brains of dementia patients showed quinolinic acid neurotoxicity. This acid kills nerve cells in the brain, leading to brain dysfunction and ultimately death. ... Quinolinic acid is part of a biochemical pathway called the kynurenine pathway. The activation of that pathway is also found in other major brain diseases including Huntington's disease, stroke, dementia and schizophrenia. ... There are several drugs which can block this pathway, which are already under investigation by our laboratory and others ... Quinolinic acid may not be the cause of Alzheimer's disease, but it plays a key role in its progression ... While we won't be able to prevent people from getting Alzheimer's disease, we may eventually, with the use of drugs, be able to slow down the progression."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=28644

Stem Cells To Overcome Aging
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From EMBO Reports, an excellent article (and some bold claims) on the prospects for stem cell research and regenerative medicine to overcome age-related degeneration: "All ageing phenomena - tissue deterioration, cancer and propensity to infections - can be interpreted as signs of ageing at the level of somatic stem cells. As the regenerative prowess of a living organism is determined by the ability and potential of its stem cells to replace damaged tissue or worn-out cells, a living organism is therefore as old as its stem cells. ... an understanding of the molecules and processes that enable stem cells to initiate self-renewal and to divide, proliferate and then differentiate to rejuvenate damaged tissue might be the key to regenerative medicine and an eventual cure for many diseases."

Link: http://www.nature.com/embor/journal/v6/n1s/full/7400436.html

Ray Kurzweil Interviewed by Charlie Rose (Video)
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It does seem to be multimedia week this week, doesn't it? For those who'd like to listen to futurist Ray Kurzweil discussing his views on radical life extension and the future of technology - as presented in his books Fantastic Voyage and The Singularity is Near - here's an Akamai link to the Windows Media Format video of his appearance with Charlie Rose. Grab it while it's still there!

Aubrey de Grey and Calorie Restriction
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It's no great secret in the healthy life extension community that biomedical gerontologist Aubrey de Grey - the driving force behind the Strategies for Engineered Negligible Senescence and half the driving force behind the Mprize for longevity research - doesn't think that calorie restriction (CR) is a practical strategy for extending life span to any significant degree in humans. Which isn't to say that he thinks calorie restriction is no good - it's quite clear from ongoing studies that the health benefits are very impressive. April Smith's recent post on the subject is worth reading. Aubrey comments:

For the avoidance of doubt: though I think that CR will probably give humans only 2-3 years of extra lifespan at most, I certainly don't disapprove of it -- the health benefits are clear, as shown in the Holloszy and Fontana work, and even 2-3 years may make a big difference to quite a lot of people. So I approve of CR.

Discussions on the efficacy of CR in extending human life span are a touchy subject in some quarters - but science is science and will keep moving forward towards a definitive answer to match what we know about CR and life span in smaller mammals. You can find Aubrey de Grey's paper explaining his view on CR at his website. As April tell us, Michael Rae - noted CR practioner and also Aubrey's research assistant these days - has penned a rebuttal to that paper that awaits publication:

MR wrote a rebuttal to Aubrey's article about weather and CR that was accepted by Gerontology, but he had to withdraw it due to page charges. Now he's resubmitted it to another journal and is waiting for approval.

I'm looking forward to seeing it; Michael writes a good paper when he sets his mind to it. You can see some of his work at the Longevity Meme and here at Fight Aging!

How Does Regeneration Work?
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Transfusions of adult stem cells have shown promise in human trials, but researchers are still searching for definitive conclusions on how these therapies work. From EurekAlert: "Adult stem cells can be found locally in various tissues and organs, and we have presumed that they are participating in the repair and maintenance of organ functions. The controversial idea is that adult stem cells have the potential for transdifferentiation; in other words, that they are able to transmutate from one type of organ cell to another. ... [Scientists] have discovered by a number of different experimental approaches that mesenchymal stem cells only show a rudimentarily developed potential for transdifferentiation processes. All cases in which functional skeletal muscle cells arose from mesenchymal stem cells were based on the fusion of stem cells with already differentiated muscle cells."


Link: http://www.eurekalert.org/pub_releases/2005-08/m-tro080405.php

The Monster In Your Mitochondria
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Medical News Today reports: "'Complex I' is the first of several protein complexes or enzymes in mitochondria and bacteria that work together in the 'respiratory chain' to produce the energy that all cells need to function ... Complex I is one of the largest iron-sulphur cluster and protein assemblies and is sometimes called the 'monster' by scientists." Researchers are making progress in understanding the monster and have discovered an unexpected cluster involved in suppressing free radical production, thought to be a source of age-related damage to your cells: "It is important now to explore, by genetic modifications, how changes to this cluster might affect the rate of oxygen radical production. This might help us to learn more about longevity and aging."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=28588

The State of Memes and Persuasion
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As I'm sure you've noticed, both this blog and its parent site the Longevity Meme aim as much at providing a guideline to newcomers to healthy life extension as catering to advocates and those in the know. If you come here often, you'll see certain themes repeat themselves - and one would hope that you'll see few items that would be challenging for a new visitor. These websites exist because there are certain collections of ideas, memes, that I think need greater play in our culture of information. Interesting and useful repetition, restatement and elaboration are the stock tools of the advocate who seeks to persuade and educate, and I certainly indulge myself.

I've long noted that the future is not a conveyor belt of ever more wonderful medicines and technology. The future is an ongoing product of all our actions - just because the futurists propose to see something on the horizon doesn't mean that it will be built. Building requires investment, and significant investment only happens in the presence of widespread support and understanding of the intended goal. If we all sit back in expectation of a conveyor belt future, we'll end up with nothing. More pertinently, we'll all end up crippled, suffering and eventually dead from age-related conditions that could have been cured if we'd just stood up in support of medical research back in the day.

What are the memes I am attempting to promote? I think that the following division of ideas and concepts is helpful:

1) Radical life extension is possible:

There is every reason to believe, based on the best available science of the present day, that the healthy human life span can be indefinitely extended - given the tools and applied technologies to do so. How long will it take to develop these technologies? That's up to us.

2) Stay healthy today in order to extend your healthy life span further with the technologies of tomorrow:

The concept of escape velocity in healthy life extension has been getting a lot of play in the past six months. We don't have to - and won't - jump to radical life extension in one go. Medical technology will improve a little at a time, giving us a year here and a year there. These years add up: each of them is another year in which scientists can come up with better, more effective life extension medicine. Eventually, the medical research community will be adding years faster than aging can take them away - escape velocity! Will we be alive and healthy to see it? That's up to us.

3) Support the medical research most likely to lead to healthy life extension:

The future is up to us. Public acclaim and desire leads to funding and investment in new technologies. If you want to live a longer, healthier life, then be an informed advocate, and informed consumer. Snub commercial "anti-aging" nonsense. Support stem cell research, tissue engineering, mitochondrial science and Strategies for Engineered Negligible Senescence. Donate to the Mprize for longevity research. Speak out, give the world your views on living a longer, healthier life - because the future of healthy life extension medicine is up to us.

4) As I may have mentioned once or twice, it's up to us:

If we all shirk and backslide, then we'll all age, degenerate, suffer and die - it's that simple. If we want a future of better medicine, cures for age-related disease and far longer, far healthier lives, then we have to stand up and do something about it. It's up to us.
More On Carbon Dating Tissue
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The New York Times has more on a recent advance in radiocarbon dating of tissue in the body. A lot of you is not as old as you might think. From the article: "But if the body remains so perpetually youthful and vigorous, and so eminently capable of renewing its tissues, why doesn't the regeneration continue forever? Some experts believe the root cause is that the DNA accumulates mutations and its information is gradually degraded. Others blame the DNA of the mitochondria, which lack the repair mechanisms available for the chromosomes. ... 'The notion that stem cells themselves age and become less capable of generating progeny is gaining increasing support,' Dr. Frisen said. He hopes to see if the rate of a tissue's regeneration slows as a person ages, which might point to the stem cells as being what one unwetted heel was to Achilles, the single impediment to immortality."

Link: http://www.nytimes.com/2005/08/02/science/02cell.html?pagewanted=print

Changing The Day You Die
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A morbid headline, but an accurate portrayal of the subject matter from the Belfast Telegraph - I have to admit that I prefer to think of healthy life extension and the search for actuarial escape velocity as a positive, continuing process of scheduling additional days of healthy life. Finality can wait. The message here: take care of your health today and increase your chances of being alive and active to benefit from the life-extending medicine of tomorrow: "We are now beginning to talk about curing old age. It really does look as though there is no fixed, non-changeable upper limit to life span. ... All the metabolic side-effects whose accumulation is eventually pathogenic are amenable to repair."

Link: http://www.belfasttelegraph.co.uk/news/features/story.jsp?story=655094

A Dose Of Common Sense
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It's somewhat refreshing to see an article on general health and aging in the mainstream press that demonstrates plain common sense. From the Washington Post: "Despite the constant promotion of products claimed to extend life and prolong vigor, nothing you can buy in a box, bottle or tube has been shown to extend anything other than your credit card balance. ... You've probably heard about promising research, in animals and to some early degree in humans, about benefits of severe caloric restriction - say, cutting daily calories by about a third. ... the results on smaller caloric-restriction studies in humans have been stunning: Cholesterol levels, blood pressure and other major risk factors for heart disease plummeted, along with risk factors for diabetes."

Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/08/01/AR2005080101244_pf.html

Kurzweil on Achieving Immortality Through Technology
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Since I'm pointing out audio interviews at the moment, here is one with Ray Kurzweil:

In the near future blood cell sized robots called nanobots will travel our bloodstreams making repairs. He sees this as one part of a larger trend of achieving immortality through technology.

Kurzweil has another new book that covers the topic - The Singularity is Near, When Humans Transcend Biology - coming out soon. This is more of a focus on the path to what he described as "Bridge Three" in Fantastic Voyage: the logical end results of applied nanotechnology and bioengineering put to work extending the healthy human life span. It'll be a good few decades before we see any of this reduced to practice, however, which is why it is important to take good care of your health now - it'd be a shame to miss the boat on actuarial escape velocity and radical life extension just because you let things go to seed.

Genetics Of The Aging Brain
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(From Medical News Today). You may recall that it wasn't all that long ago that researchers announced results from a study of changes in gene expression with age in the human kidney. Now we have more of the same, but for the aging brain. Researchers "found a pattern of age-related changes in the expression of hundreds of genes. ... One common theory of aging holds that damage is done to DNA and proteins by "free-radicals" (highly reactive molecules produced by the metabolic activity of mitochondria). It predicts that more metabolically active tissues will show greater age-related differential gene expression. The results of this study support this theory since the more metabolically active cortex shows a greater reduction in gene activity." Use it more and it tends to wear out faster.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=28451

Innovation In Nanoscale Engineering
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(From the BBC). Add a little nanoscale engineering and even old-fashioned cancer treatments can be made much more safe and effective: "The MIT team tackled the problem by creating a structure for the nanocell that resembled a balloon within a balloon. The researchers loaded the outer membrane of the nanocell with an anti-angiogenic drug and the inner balloon with chemotherapy agents. They also created a surface chemistry which allowed the nanocell to evade detection by the immune system." Very clever - imagine what the future has to offer if this is an example of the first generation in applied ingenuity and comparatively basic nanoscale work.

Link: http://news.bbc.co.uk/2/hi/health/4715739.stm

ABA Review Essay On Longevity Science
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Glenn Reynolds of Instapundit has posted an online copy of his recent review essay from the ABA's law and technology journal, entitled Live Long - And Prosper? "It seems that we have arrived at some sort of 'harmonic convergence' of scholarship on the subject of longevity and life extension - so much so that the journal Gerontology published an entire symposium issue on the subject as this Essay was in progress. That being the case, it is worth taking some time to look at longevity and life extension and to think about where we might be heading. ... There is now some reason to think that lifespans may become considerably longer in the not-too-distant future."

Link: http://www.instapundit.com/lawrev/jurimlivelong2.htm

Australian Podcast Interview With Aubrey de Grey
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We certainly live in an eclectic, ever-shrinking world; the internetless realm of my youth seems like a very long way away at times, almost a different planet. As an illustration of the way in which geographical boundaries hindering dispersed advocacy movements largely vanish in the presence of broadband, here we have an Australian podcast interview with biomedical gerontologist Aubrey de Grey on the topic of healthy life extension and his Strategies for Engineered Negligible Senescence (SENS):

My guest tonight, Dr Aubrey de Grey, biogerontologist from the Department of Genetics, University of Cambridge, UK, is the man leading the field in this incredibly exciting research. ... Out of all of the interviews I've done in the last 8 months, I have to say this is personally the most exciting. Getting to assist guys like Dr de Grey to get their message out to the wider population makes this podcasting thing worthwhile.

The direct link to the MP3 is here. See what you think.

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