Cultural norms of knowledge, belief and intent bear no necessary relationship with fact, sanity and sense. Humans are hardwired to respect the norm: any set of concepts widely held are valued highly for that fact, while new or rare ideas have a real hurdle to acceptance. One aspect of this facet of the human condition is illustrated by Russell Blackford: science is by its nature a process of generating new ideas that are not widely held by the world at large, even when those ideas have come to be generally accepted within the scientific community. Hence demonstrating truth through science is by necessity a great deal harder than it might be in a more just universe:

Bloom and Weisberg conclude that resistance to scientific thinking will continue beyond childhood into adulthood if the scientific claims are contested within the individual's society. The resistance will be epecially strong if a non-scientific alternative (1) has currency in the society, (2) is rooted in intuitive understandings, or common sense, and (3) is championed by people who appear to be reliable and trustworthy.

He goes on to talk about magical thinking - of which we see a great deal in any broader discussion of longevity and health - but let's stick with the power of the norm for today. We advocates for healthy life extension should not lose sight of the fact that we're delivering a message that is still far from the norms, and thus appears deeply strange to a great many folk - for no other reason than it is unusual in their experience, novel to them. "Deeply strange" is going to get you rejected out of hand, no matter what the merits.

Raising awareness and generating an environment of support for funding successful longevity research requires a certain amount of raising the water level so that boats can float. Steady repetition, restatement and messaging through many channels and in many different ways are the coin of the realm; this has been taking place for some years now, and the results are beginning to be apparent. Take a look at a recent article on cryonics from a popular perspective, for example; it should remind us that there's a whole world of outsiders looking in out there, but it's far less negative than similar items from past years.

"I drive by the place twice a week," said Helgeson, "and I just can't believe Ted Williams's head is hanging in there. Either someone in his family is a lunatic or has a lot more faith in science than I do."

Cryonics is eminently sensible, yet, like all ideas that are not presently the norm, it must leap the hurdle of being something new for most people. This is one example of many I could draw for those of us interested in living much longer, healthier lives. The biggest challenge we face is not the medical research and development yet to come, but convincing a sufficient number of people to support that effort - in effect to make working towards healthy life extension a norm.

Technorati tags: advocacy, life extension

Posted by Reason at 10:12 PM
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The economists of the blogosphere are pondering the nature of a post-mortal society, an activity that strikes me as thinking hard about what to do with the pits before you've planted the cherry tree. A great deal of work lies between here and there - we are barely starting on the serious effort to defeat aging through medical science.

The basic consequences of living longer are fairly straightforward, in the economic worldview at least: your time preference extends outwards. In theory that means that individuals are increasingly less likely to trash the future for the sake of the present; a long time preference looks a lot like wisdom when seen from the side. What that means for a society of like-minded and very long-lived folk is anyone's guess; no simple trend in individual averages extrapolates out to group dynamics. But it seems to me to be the case that the last factor of two increase in life expectancy produced changes in human society more remarkable for their subtlety than anything else.

Or at the very least, it's hard to pick out what is longevity versus other technological advances and wealth creation.

Would Ageless People be Libertarian?

If aging were curable, would people feel less inclined to expand government?

These days, I tend to think of the issue of the size of government as essentially a power struggle between capitalists and anti-capitalist intellectuals. I don't see how a cure for aging resolves this conflict.

...

If an ageless 150-year-old behaves like an old person, then he or she will have a goal of stability. That might mean a very non-libertarian attitude. But I am not sure that ageless people will have attitudes that are elderly or not.

Would immortals be libertarian?

If we assume monotonicity (and why shouldn't we?), we can draw inferences from societies with short life expectancies. They are extremely superstitious, willing to entertain tyranny, and hardly libertarian. Try teaching Henry Hazlitt in the Congo. More generally, pending death makes us think of honor, patriotism, and in-group solidarity.

The Risk of Immortality

Immortals would have far more to lose by dying in an accident than the average guy who kicks the bucket at before passing the century mark--particularly so, since the immortal never experiences age-related decline--which will make them far more risk averse. Risks that seem quite tolerable to normal human beings, like driving on the freeway or allowing aircraft to fly over your house, will be completely reckless (even insane) to an immortal.

Put more effort into making longevity medicine a reality, and increase your chances of being able to debate this sort of thing for as long as you care to. Not to mention living to see what a post-mortal society actually looks like. From where I stand, that's a much more interesting brand of economics as human action.

Technorati tags: economics, libertarian, life extension, politics

Posted by Reason at 10:40 PM
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Have you noticed how much slower medicine seems to move than other fields of development? It takes a decade to move from news out of the laboratory to first therapies commercially available; compare that to the hectic rush and invention of the computer hardware industry. You can lay every last day of delay and cost down to regulation; just look at the gauntlet that has to be run:

Although some people talk of an anti-aging pill, it is more likely that research will yield therapies that target specific age-related diseases - a vaccine to prevent Alzheimer’s disease, for example. In either case, the road to such a medicine is long and often fraught with wrong turns, dead ends, and detours. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), it takes 10 to 15 years and up to $1 billion to develop one new medicine from the time it is discovered to the time it is made available as an FDA-approved therapy. Why does it take so long and cost so much? Because drug discovery and development is a time- and labor-intensive process involving thousands of people, from researchers at colleges and universities, to scientists and professionals at pharmaceutical companies, to participants in clinical trials.

Drug discovery and medical research is in fact no more inherently costly or time-consuming than research into new forms of computer hardware - a field that is just as exciting at this present time. But medical research and development is made costly by the heavy boot of regulation for the sake of regulation: an institution of rules and rule-makers that has come to stand for nothing beyond its own self-propagation.

If anything is to be the death of us in this era of potential and revolution in biotechnology, it will be that regulation scared away the innovators, suppressed the discoveries that might have been, and kept disruptive, effective new technologies away from the marketplace for years past their time. When progress is made costly, progress becomes slow - but worse, an entire range of invention and endeavor simply vanishes, priced out of existence.

But most people can't see the invisible cost - the cost of things that might have been. Most people suffer a great failure of the imagination when it comes to anything the government has a hand in; they can't imagine it any other way, even when presented with thriving examples from other industries. Medicine could be as dynamic, inventive and productive as the computer hardware industry, or the fashion industry. But it is not, and so we will suffer because progress will be slow and the delivery of goods funneled through organizations so regulated that their employees and owners have no incentive to do a good job.

Technorati tags: libertarian, medicine

Posted by Reason at 11:50 PM
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The mitochondria in our cells take in food and oxygen and use it to produce ATP, a chemical used as fuel to power the rest of the cell. This is known as mitochondrial respiration, or cellular respiration. In the process, oxygen radicals - also generally known as free radicals or reactive oxygen species (ROS) - are produced. These damaging byproducts go on to wreck other molecules and cellular mechanisms in a drawn-out process that is one part of degenerative aging. This is the essence of the mitochondrial free radical theory of aging - that we are slowly slain by the accumulated toxic byproducts of essential metabolic processes. Evolution cares not, because we've long passed the test of reproductive fitness by the time our bodies are choked with metabolic pollutants.

One might think that the faster metabolism runs, the worse the situation becomes: more oxygen consumed means more ROS unleashed to cause harm. This is not in fact the case, as the relationship between the metabolic rate - the rate at which oxygen is consumed - and the rate at which ROS are created is not linear. Rather like cars, levels of fuel efficiency and average time to next breakdown for the engine vary widely depending on speed and circumstance - and cars can neither repair themselves nor change significantly to adapt to new circumstances, both of which complicate the picture for human metabolism.

For humans, most of the simple things that reduce the rate at which ROS are generated also speed metabolism. Exercise and calorie restriction with optimal nutrition, for example, raise metabolic rate and are demonstrably good for healthy longevity - better for most folk in the long term than anything yet produced by medical science. Here's a paper that provides a succinct overview of the situtation:

Various recent investigations relevant to the study of aging mechanisms have recently found that increases in longevity during dietary restriction can occur together with lack of decreases or even increases in [oxygen, or O(2)] consumption. This is frequently interpreted as contradictory with the mitochondrial free radical theory of aging. But this is based on the erroneous assumption that increasing O(2) consumption must increase the rate of mitochondrial oxygen radical generation. Here it is shown that the opposite occurs in many important situations. Strong decreases in absolute and relative (per unit of O(2) consumed) mitochondrial oxygen radical production occur during aerobic exercise bouts, chronic exercise training, and hyperthyroidism, and notably, during dietary restriction. Mitochondrial oxygen radical generation is also lower in long-lived birds than in short-lived mammals of similar body size and metabolic rate. Total rates of reactive oxygen species generation can also vary between tissues in a way not linked to their differences in oxygen consumption. All this indicates that mitochondrial reactive oxygen species (ROS) production is not a simple byproduct of mitochondrial respiration. Instead, it is regulated independently of O(2) consumption in many different physiologic situations, tissues, and animal species. Thus, the apparently paradoxical increases in O(2) consumption observed in some models of dietary restriction do not discredit the mitochondrial free radical theory of aging, and they can further strengthen it.

Technorati tags: aging, calorie restriction, metabolism

Posted by Reason at 8:12 PM
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The folk of the Calorie Restriction (CR) Society are continuing their efforts to raise funds to broaden human CR research with a fundraising event in August. As for many successful health-oriented organizations, the Society prospers through close ties with the research community - just look at any of their conferences in recent years. As Mary Robinson relates:

At last year's CR Conference, we all told Dr. Spindler that we would raise the money for him to do a human study on gene expression in CR - on us. This is a cool idea in so many ways. From all the moaning and groaning from the calorie restriction researchers at the conference, it is very clear that they are having a hard time getting funding from NIH. It's not a disease, after all - aging. Or is it? Spindler also thought it would be hard to get subjects. We all had quite a chuckle over that one. Told him that he was looking at a room full. Dr. Fontana vouched for us - and was just as amused, I think. So, we decided as a group to give him no excuse not to study us. He's too fond of rats, IMHO. It seems to me that most biologists are very fond of rats, mice, or worms or yeast.

April Smith has more details on the fundraiser:

People from all over the world will converge from Friday, August 10 through Sunday, August 12 on the village of Tarrytown, New York, near Sleepy Hollow, where Washington Irving spun his yarn of "The Headless Horseman." But this is a meeting of facts, not fiction. It is a workshop on calorie restriction, the only scientifically proven way to slow aging .

...

The workshop is a benefit for the continuation of a milestone research project on the effects of calorie restriction on humans. Initiated in cooperation with the Calorie Restriction Society by Drs. Luigi Fontana and John Holloszy, of Washington University Medical School in Saint Louis, the first two phases of the research have discovered new knowledge that allows people everywhere to better understand how to prevent disease associated with aging.

A highlight of the workshop will be presentations by Dr. Fontana and by Dr. Stephen Spindler, whose genetic analysis of calorie-restricted animals has garnered worldwide acclaim. Dr. Spindler will lead the exploration of the genetic and cell signaling patterns of human calorie restrictors in Phase Three of the research whose funding is spearheaded by the Calorie Restriction Society.

Contributions of $1,000 or more for the research project are requested for anyone wishing to register for the workshop. As a special "thank you" for this support, workshop attendees will receive a glucose control kit that includes a glucometer, testing strips, and stylus. A copy of NutriBase, the leading dietary tracking software, will be available for participants to use while they are at the workshop and to take home to try. Participants will also receive a bibliography and copies of the charts presented at the workshop.

All who are interested in slowing the ravages of aging are invited to take part in the warm, friendly immersion experience of the Calorie Restriction Workshop, where they can meet kindred spirits, exchange ideas, and make friendships that may last for a very long lifetime. Attendance is limited so that a personal experience can be provided to all attendees.

The practice of calorie restriction and exercise is most likely going to do more for your chances of avoiding many of the common age-related diseases than any drug presently in the pipeline. This isn't the future of longevity medicine - it won't take too many more years for research to actually repair age-related molecular damage rather than just slow the accumulation, a huge jump in potential effectiveness - but it is free and it is available now. Anyone can do it.

Taking better care of your body makes a real difference over the long term, and increases your chances of being alive and in good health when the real longevity medicine becomes available - some decades from now, when adding decades of rejuvenated health to the lives of those already aged will be a realistic proposition.

Technorati tags: activism, calorie restriction

Posted by Reason at 1:31 PM
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Around the time I was penning the first version of the anti-aging topic page over at the Longevity Meme, Binstock had already put out a much more eloquent paper on much the same themes. There are no unique ideas or approaches in a world full of people paying attention:

This article interprets the contemporary war on anti-aging medicine as largely an attempt by established gerontological researchers to preserve their hard-won scientific and political legitimacy, as well as to maintain and enhance funding for research on the basic biological mechanisms of aging. First, it recounts the difficult struggle of U.S. biogerontologists to join the scientific mainstream in terms of legitimization and public funding. Second, it examines how elements of a contemporary anti-aging movement seem to threaten the hard-won public legitimacy of established gerontological researchers and practitioners. Third, it looks at the "boundary work" responses of the gerontological community to the anti-aging movement. Finally, it assesses the consequences of the war on anti-aging medicine to date.

The public at large, led by a media with economic incentives to be ignorant, doesn't tend to distinguish all that well between two similar topics. Human nature at work, but that means that scientists find their funding threatened by the branding of "anti-aging" in the marketplace. Here are a couple more papers on the same topic, further illuminating the ongoing battle over understanding, support, legitimacy and funding:

Contentious terminology and complicated cartography of anti-aging medicine:

Serving as an introduction to the cultural significance of the contemporary emergence of anti-aging medicine, this article outlines some of the distinctions and controversies regarding the usage of the term "anti-aging medicine." By sketching out the complex field of researchers, practitioners, organizations, companies it is clear that "anti-aging medicine" is a highly contentious term that means different things to different groups. Thus, analysis demands a keen attention to contextualizing its usage. However, despite the critically important distinctions in how "anti-aging medicine" is used and what it connotes both to the user and the audience, the core principle of anti-aging is the notion that aging can be targeted for biomedical intervention. It is the orientation toward this explicit goal that marks anti-aging medicine. While neither advocating for/against anti-aging medicine nor excavating the large body of biological literature, this ethnographically researched article explicates the cultural use of "anti-aging medicine" and maps out its main varieties, controversies, stakes, and challenges.

Anti-aging medicine and research: a realm of conflict and profound societal implications:

Biogerontologists have recently launched a war of words on anti-aging medicine. They seek to discredit what they judge to be fraudulent and harmful products and therapies, and to distinguish their own research from what they regard as the pseudoscience of anti-aging injections, special mineral waters, and other services and products. Yet, many of these biogerontologists are themselves trying to develop interventions that will actually slow or arrest the fundamental processes of human aging and substantially extend average life expectancy and maximum life span. Achievement of these biogerontological goals would drastically alter the nature of individual and collective life, radically transforming virtually every social institution and norm. Biogerontologists who are engaged in anti-aging research need to undertake more active leadership in helping the public to understand their goals, to deliberately consider the implications of their fulfillment, and to begin thinking about ways to shape those ramifications in constructive fashions.

The paper above and the social study below cut very much to the core of it: the end goal of extended healthy life - giving more time to develop technologies to extend life even further - is profound and of greater value than any other grail of the immediate future. People who grasp and internalize that value are driven; understanding that moving along the wrong path means the difference between life and death for billions lends real weight and passion to differences of opinion.

Anti-aging medicine: a patient/practitioner movement to redefine aging:

Anti-aging medicine is a broad term that may comprise groups selling remedies over the Internet, companies touting the "anti-aging"ness of their products, practitioners who work outside of scientific medicine, and practitioners of anti-aging medicine in clinics who believe that their work is strictly scientific. This article, drawing from more than 3 years of ethnographic interviews, participant observation in clinics and conferences, and a review of the literature, considers the last group. It examines the involvement stories of anti-aging medicine practitioners in two Western United States metropolitan cities. These stories reflect the practices of anti-aging medicine practitioners and the accompanying rationale for involvement. Often originally patients themselves, practitioners frame their involvement with the anti-aging movement in three ways. First, they describe aging as it is currently experienced as a time of decline, suffering, and weakness. This anguish is not inevitable, they argue, and their work toward treating aging biomedically is situated as clearly moral. Secondly, intense frustration with the current biomedical environment has motivated practitioners to look for other ways in which to practice: anti-aging medicine is their chosen alternative. Finally, with dramatic expectations of future biotechnologies and disdain for current medical treatments of old age, anti-aging practitioners embrace a scientific revolutionary identity.

The mainstream of genontology does not publicly share whatever private enthusiasm its members have for rapid progress in developing therapies for aging, for they have - perhaps inadvertently - constructed a community in which that enthusiasm is the instant death third rail for funding. On the other side of the fence, enthusiasts and believers of the anti-aging marketplace (as opposed to the pure businessmen and frauds) are invariably taking the all too human shortcut of belief over science, and pushing things that don't work or otherwise cannot be shown to do much good.

As is so often the case, neither of the big bulls kicking up dust and butting heads is where you should be looking if you want to find the best path forward. Change must happen for either side to be the source of more rapid, sweeping progress. At the present time, attention and funds are better pointed elsewhere.

The better path I have in mind is support and growth for that presently small part of the scientific community that is interested in rapid progress in extending the healthy human life span, not afraid to talk about it, and in no danger of falling into the pit of the marketplace by jumping the gun and pushing products that don't work. Should this group succeed in gaining more influence, they will lead both the mainstream of gerontology and the anti-aging markplace into the needed changes that will produce more positive contributions to the future of healthy longevity - this much has been demonstrated from progress to date.

Technorati tags: anti-aging, life extension

Posted by Reason at 8:16 PM
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There is a small but rich vein of science fiction (or alternate history now, take your pick) set at various times in a past couple of decades that might have been - had the look and feel of the 70s continued unabated, as though the decade never ended, and the world in fact worked the way it was thought to back then. One might look at Bug Jack Barron, for example, or some of Spinrad's other works.

This was brought to mind by Alexy Olovnikov and his "chronomeres," which I stumbled over today in their glorious entirety. While I'm sure this fellow is quite serious in his endeavors, plugging away at his theory in isolation and managing to make his way into serious journals, it has all the look and feel of an alternate history of aging science taken from a world in which the 70s never ended - and in which aging actually works the way it was thought to back then. A world in which growth hormone, pineal glands and lunar cycles mesh with DNA science, aging is a programmed phenonenon regulated at the level of organs rather than cells and molecules, and the discoveries of the 1990s and 2000s never happened.

Hypothesis: Lifespan is Regulated by Chronomere DNA of the Hypothalamus

As the basis for the lifelong clock and as a primary cause of aging, a process of shortening of hypothetical perichromosomal DNA structures termed chronomeres is proposed in the [central nervous system]. The lifelong clock is regulated by the shortening of chronomere DNA in postmitotic neurons of the hypothalamus. Shortening of these DNA sequences occurs in humans on a monthly basis through a lunasensory system and is controlled by release of growth hormone discharged from the anterior pituitary directly into the hypothalamus via local blood vessels. In adults, this process is under control of the pineal gland. It is further proposed that different forms of Alzheimer's disease (AD) are caused by somatic and inherited deletions of chronomeres followed by a further abnormally accelerated decrease in their activity, resulting in failures of neurotrophic and neuroendocrinal activities and in various cellular imbalances.

Lunasensor, Infradian Rhythms, Telomeres, and the Chronomere Program of Aging

According to the redusome hypothesis, the aging of an organism is determined by the shortening of chronomeres (small perichromosomal linear DNA molecules). In this paper, a presumptive role for infradian hormonal rhythms is considered. Endogenous infradian rhythms are supposed to actively interact with those hormonal shifts which are governed by an exogenous infradian gravitational lunar rhythm. As a result of this interaction, the so-called T-rhythm is formed. Peaks of T-rhythms are used as the pacemaker signals to keep the life-long "clockwork" of the brain running. The "ticking" of this clock is realized by the periodically repeated shortening of chronomeres in postmitotic neuroendocrine cells, which occurs just at the maxima of T-rhythms. Shortening of telomeres in mitotic cells in vivo is a witness of the aging of the organism, but not the cause of aging. The primary cause of aging is shortening of chronomeres, the material carriers of a temporal program of development and aging. To recognize exogenous gravitational infradian rhythms, a special physiological system - the "lunasensor" system - evolved. It is assumed that it is a necessity to have a lunasensor as a particular variant of sensors of gravitation.

I'm rather hoping that second abstract above jumps out at you as absolutely alien to most of the aging science you've seen in the past few years. Here's an article from a few years back that's an easier read:

There are no genes of ageing, but there is a program for it

Early in the 70s of the 20th century, Russian researcher Alexy Olovnikov forecast existence of the chromosomes' end sequences - telomer, which shorten after each cell division. Aa lot of scientists believe now that telomere shortening leads to cell ageing. However, A.M. Olovnikov is convinced that telomer shortening is only the witness of ageing, and special DNA molecules - chronomeres - are responsible for ageing processes. Chronomeres are located in non-dividing cells of the cerebrum. So far, this is only a hypothesis based on the tremendous experimental material collected by Russian and foreign researches within the recent years.

It has to be said, this all triggers my crank sensors (and then some), for all that these papers appear in respected journals. Go hunt the scientific internet for signs of chronomeres and you'll meet with little but Olovnikov and the sound of crickets. A hypothetical component to the well-mapped cellular nucleus just isn't going to fly in this day and age, and the rest of it is all quite amazing - glands and hormones as giant controlling levers that can explain away aging. It seems like the aging science equivelant of building a working Babbage machine, or a computer constructed with miniaturized valve technology as it could be built today - a work of speculative art, but of little use to progress.

If you'd like to look at more modern and useful theories of aging, you might start with the Strategies for Engineered Negligible Senescence, which is built upon those theories with the best evidence and most active research communities behind them.

Technorati tags: aging, science

Posted by Reason at 8:07 PM
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We've all experienced a preview of what it's like to suffer the effects of aging, even those of us who haven't tried on the aging simulator suit. What preview is that? Well, think back to the last time you were significantly ill - home from work, in pain, feeling sorry for yourself, and struggling with the list of simple tasks that still absolutely had to be accomplished regardless. Every simple thing seems like a mountain in such miserable times, never mind the hard stuff.

Now imagine all of that stretching forward for years; unending medical costs and no real prospects for improvement. That is the present end state of degenerative aging in a nutshell. Why aren't you doing more to help avoid this fate?

We live in an age of near-unlimited potential in the advance of biotechnology and medicine, yet very little in the way of resources is directed towards repairing the damage of aging. Potential is worth nothing if few are working on it.

So help yourself out by helping to bring forward the date on which humanity defeats aging. If we miss that boat, and consequently suffer years of the ugly realities of aging, then we only have our own inaction to blame.

Technorati tags: aging, life extension

Posted by Reason at 9:31 PM
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Research prizes for medicine work, which is we're seeing more of them these days. It's very hard to institutionalize innovation, to build a conveyor belt for radical new ideas, but the contest model has traditionally worked well for this purpose. If you look back at the history of prizes for scientific and technical achievement, they draw healthy multiples of the prize purse in funding for novel lines of research, and empower worthy developers who would traditionally not have made much headway in the mainstream. The Mprize for longevity research is perhaps the most familiar initiative for readers here.

a scientific competition designed to draw attention to the ability of new technologies to slow and even reverse the damage of the aging process, preserving health and wisdom in a world that sorely needs it.

All this considered, I'm not too surprised to see research prizes launched in areas of medicine traditionally considered well-funded:

Medical researchers teamed up with hedge fund managers on Wednesday to offer a new million-dollar prize for the best new idea for cancer research in the hopes of kick-starting innovative approaches.

...

"I have seen firsthand how many ideas with incredible potential never reach fruition," Curhan said. "We will only make significant progress in cancer research by learning from each other's successes and mistakes, and by building on each other's knowledge."

People who want to make individual contributions to a particular researcher, as opposed to making a general donation to a charity, are also invited to look at the site.

Curhan stressed he does not believe the NIH is unimaginative in funding research.

"Most of the work is incremental just because of the long tradition and because people tend not to pick risks. And you tend to write grants to what you think will get funded as opposed to your most innovative idea," he said.

Technorati tags: medical research, research prize

Posted by Reason at 9:49 PM
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Via the Gerontology Research Group list, Pete Estep reports from the 2007 Harvard / Paul F. Glenn Symposium on Aging. Hyperlinks are added by my hand for general edification, as usual:

I attended the Glenn Symposium on Aging today at Harvard Medical School. The speakers in order were Elizabeth Blackburn, Doug Wallace, Marcia Haigis, Nir Barzilai, Pere Puigserver, Tom Prolla, Marc Tatar, Rick Weindruch, and David Sinclair. Overall, it was pretty good. I missed Blackburn and Wallace but I saw Blackburn talk earlier this year and her latest research on telomeres is very interesting.

Barzilai talked about their centenarian study. He is calling it the LonGenity study! I told him I let the Longenity domain expire just recently--which was grabbed immediately. He was a bit perturbed not to have gotten it but I didn't know he had started using the name. Anyway, they are doing some SNP studies which he did not report on. He talked mostly about LDL and HDL particle size, and he showed data suggesting that both centenarians and their offspring have larger LDL and HDL relative to controls. They also found some IGF1-R allelic variants in some small centenarians. He also talked a bit about some work in rats. They surgically removed the visceral fat in ad lib fed young rats which lived longer and showed increased insulin sensitivity relative to ad lib fed controls.

Prolla talked about the Polg mutant mouse and some recent results they've gotten on measuring mtDNA deletions (in addition to their recently published work on point mutations). It seems that deletions increase in Polg -/- homozygotes but not in heterozygotes, which might explain why homozygotes experience accelerated aging but hets do not.

Weindruch gave an update on the Wisconsin primate [calorie restriction] project. The ad lib fed animals and CR animal mortality curves appear to be diverging but the result is not statistically significant yet.

Dave Sinclair gave an update on his lab's work on Sir2 and small molecule sirtuin activating compounds (STACs). Both resveratrol and SIRT1 overexpression reduce intestinal and other cancers. Sirtris, the company Sinclair founded with Christoph Westphal, has several compounds that are both stable and activate Sir2 at 1000x lower concentrations compared to resveratrol. I asked David about the switch to knotweed extract from China and he said it is a real concern. He stopped taking resveratrol a while back in order to participate in a Sirtris pre-clinical trial.

Technorati tags: gerontology, medical research, science

Posted by Reason at 9:04 PM
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Researcher Jan Vijg's profile at the Buck Institute for Age Research includes a link to the first chapter of his recent book, "Aging of the Genome" in PDF format. Vijg stands in the school that believes stochastic corruption of the genome is at the root of aging:

Instability of the genome has been considered as a possible cause of aging since the late 1940's, when it was discovered that low, daily doses of radiation accelerated symptoms of normal aging in rodents. A connection between damage to the genome and aging was strongly supported by the discovery that heritable defects in genome maintenance are associated with premature aging - as shown in Werner syndrome and Hutchinson Gilford Progeroid syndrome. The defects present in those conditions, and other defects, have been engineered in mice and shown to cause premature aging in these animals as well.

In the past, my laboratory has generated a transgenic mouse model harboring plasmids containing the bacterial lacZ gene. These plasmids can be recovered from genomic DNA and subsequently transferred into E. coli to positively select for colonies representing a mutant lacZ-plasmid. The ratio of colonies of lacZ mutants over lacZ wildtypes is a measure for the mutation frequency in the mouse. In this way we demonstrated that, as predicted, the frequency of mutations increases with age in most tissues and cell types. Our present work is focused on unraveling the mechanisms through which aging-related mutations are induced and obtaining insight as to how increased genomic instability can give rise to some of the most common aging-related phenotypes.

The contribution of random mutations in nuclear DNA to aging is up for debate, however. Aubrey de Grey, amonst others, argues that the rise in mutation rates over time - effectively damage to the operating instructions of cells - does not contribute meaningfully to the progression of aging, at least not in comparison to the other forms of biochemical damage that accumulate over time. Why worry about something that will cause issues when you're 200 if any one of a dozen other processes will finish you off long before that?

Both sides can marshall a decent argument; areas like this are usually where science is at its most interesting.

I'm not completely following along with the argument that progeria and Werner syndrome support the contribution of stochastic damage to the genome as a meaningful cause of aging. Both conditions seem to have very specific causes: mutation in Lamin A for progeria and something buried in the kinases for Werner syndrome. Similar issues are seen - to a much lesser degree - in the "normal" old. Does that mean that the contribution of stochastic mutations to degenerative aging is made by how often damage hits a couple of very important genes relating to structural integrity of the cell? That seems implausible given the rate of damage, the sheer number of genes and sheer number of cells involved. But perhaps damage is more likely to happen to structural genes than in other places; maybe stochastic mutation in the nucleus is not quite so stochastic as some might think.

Research continues, and we shall see.

Technorati tags: aging, book, gerontology

Posted by Reason at 9:23 PM
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