$36,000
$25,176

Knee-Jerk Reactions: Alive And Well

Knee-jerk, thoughtless reactions to healthy life extension are still alive and well, as illustrated by this latest from Tech Central Station: "On longevity, Bailey discusses how techniques such as manipulation of telomeres (the tips of chromosomes, which seem to play an important role in aging) may add decades to human life spans. Wouldn't that be a good thing? Not according to bioethicist Daniel Callahan, who contends that longer lives, besides bankrupting Social Security and Medicare, would be squandered on golf games." Well obviously, we must immediately move to ensure that everyone suffers, sickens and dies on time. Heaven forbid that actual changes might occur in government programs, or that people will be alive and in good health to do the things they like. Why don't we all go out today and do something that Callahan disapproves of, how does that sound?

Link: http://www.techcentralstation.com/080105A.html

Follow The Money

PLoS Biology serves up an interesting look at the politics of embryonic stem cell research (which is to say the ongoing restrictions, blocks and threats that hold back medical progress in this field). You'll find a lot of nonsense on the supposed efficacy of monolithic government programs over more distributed or private research, but overall the article provides a good overview of the current state of play: "German embryonic stem cell scientist Oliver Brustle faces major challenges in his lab on a daily basis that have little to do with science. His country's policy on human embryonic stem cells (hESCs) is among the most restrictive in Europe. ... Despite the positive activity in many places, researchers like Gearhart and Weissman admit that it's only the best of a bad situation."

Link: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030234

Some Comments On "Should Humans Be Allowed To Live Forever?"

Nothing gets me bristling quite like questions about healthy life extension that involve words such as "allowed," "permitted" and so forth. Whatever happened to the presumption of freedom? A commenter on a post about the SENS Challenge proffers an interesting exchange for consideration:

Both Nuland and the Editor of Technology Review, Jason Pontin, made clear that they believe extending the human lifespan is a terrible thing which could adversely and irrevocably effect our species by transforming our nature in dangerous ways.

...

I therefore thought it would be timely for me to publish an exchange of letters I had with Jason Pontin. (There did not appear to be anything in Jason Pontin's letter which suggested he would want it kept private or which would be embarrassing to him.)

It certainly seems that Pontin comes to view healthy life extension in a manner similar to Leon Kass when it comes down to it. There is the presumption of central authority making decisions for us - controlling our future access to healthy life extension technologies - and the sense that "something could be done" to prevent people from extending their healthy life spans. As I've pointed out in past posts, that something is called murder, no matter how you might go about organizing or whitewashing it. See this comment from Pontin, for example:

That said, you raise the issue of personal freedom. Does personal freedom--including the freedom to life--trump all other interests? Societies traditionally limit personal freedom, even the freedom to live, for any number of reasons. I am not saying this is a good thing--but I don't think the argument of "choice" can decide whether or not Immortality is a Good Thing.

Stem Cell Mobilization

myDNA notes that "scientists have discovered how blood-regenerating stem cells move from bone marrow into the blood stream. The finding has led to the development of a new chemical compound that can accelerate this process (called stem cell mobilization) in mice - which could eventually lead to more efficient stem cell harvesting for human use." One reason researchers are searching for other sources of multipotent stem cells is that bone marrow extraction is an unpleasant, expensive procedure. Making bone marrow stem cells come out for convenient collection from blood is an intriguing alternative to attempting to use skin or fat stem cells, for example.

Link: http://www.mydna.com/genes/genetics/news/resources/news/200507/news_20050727_stem.html

Thoughts On Chronic Pain, Aging, Degeneration

Some thoughts on whether and how chronic pain and the process of degenerative aging tie together from Randall Parker at FuturePundit:

Do the various pains have a common cause? Does chronic pain indicate a generally faster rate of aging?

I'd like to see a follow-up of this study with people over the age of 50 where stem cells get extracted from knees and other regions of pain and also from the blood. The goal would be to measure telomere lengths and compare them between people with and without pain to see if people with more pain are biologically older than age equivalent people who suffer less pain. Telomeres are caps on the ends of chromosomes and their lengths provide an indication of how many times a cell has divided. The more times a cell divides the shorter the telomeres get. I bet that the people with more chronic pains have shorter telomere lengths. Also, I bet that people with shorter telomere lengths will have lower life expectancies on average.

A study that looks for correlations between stem cell age and extent of aches and pains would provide evidence for whether development of stem cell treatments should gain priority in treatment of arthritis and other diseases that cause pain with age. Advocates for Strategies for Engineered Negligible Senescence (SENS) such as Aubrey de Grey argue that it would be more productive to develop rejuvenation therapies than to try to develop treatments for every disease of old age. If aches and pains are the result of cellular aging and of a lack of young stem cells to supply replacements for repair then more rapid development of rejuvenating stem cell therapies would provide better solutions for the pains of old age than surgery, anti-inflammatory drugs, anti-pain medication, and other current approaches.

From an engineering, reliability theory point of view, it seems like a sensible proposition and certainly worthy of further investigation. Do older people who are suffering chronic pain have, on average, bodies that are more worn - more damaged - by the processes of aging?

Der Spiegel On Aubrey De Grey

Der Spiegel takes a few low shots at both biomedical gerontologist Aubrey de Grey and the concepts of radical life extension in this article. The journalist may not want to live healthily for a long time, but at least notes the important points: "The list of attendees at the world's second major gerontology conference in Cambridge, which de Grey is currently organizing, also serves as testimony to just how seriously the scientific world takes his theories. ... Most medical research nowadays is devoted to cancer, cardiovascular diseases and diabetes. We have powerful lobbies for diseases, but not for aging. ... in theory, a human being would live only 14 years longer if medical science could eliminate these leading causes of death. But bio-gerontologists believe that if one could prevent aging itself, people wouldn't fall ill in the first place - or at least not until much later in life."

Link: http://service.spiegel.de/cache/international/spiegel/0,1518,druck-367285,00.html

Aubrey de Grey on the SENS Challenge

A spirited discussion has been taking place on the Gerontology Research Group list with respect to the $20,000 SENS Challenge issued by the MIT Technology Review yesterday. Some folks in favor of the whole venture, some against, but here are biomedical gerontologist Aubrey de Grey's thoughts in response to other comments and an anecdote from biochemist Steven Spindler regarding the perniciousness of journalists:

Steve Spindler has summed it up best -- and I can add to his story by telling you that he did so good a job of refusing to ridicule me that the broadcaster (NBC) never aired the segment. The challenge has been brought into existence as a joint enterprise by Technology Review and the Methuselah Foundation. The reason from TR's point of view is that they have done themselves a lot of harm by doing a hatchet job on me without being able to back it up with authoritative names and they're keen to remedy that. (Jason Pontin is actually very ambivalent on the desirability issue -- one should not interpret Sherwin Nuland's views as representing Jason.) The reason from my (and [the Methuselah Foundation]'s) point of view is much more charitable: I know that most of my colleagues are inclined to be less conscientious than Steve when asked to opine on me, and I also know why, namely (a) that my conclusion in terms of potential life expectancy is very extreme and thus politically unpredictable, and (b) that the particular approach I advocate, the piecemeal engineering approach, is antithetical to mainstream thinking and thus tends to threaten funding for work that is currently in favour. The fact that I have no experimental training is an easy hook upon which to hang a curt dismissal of anything uncomfortable that I might have to say. I am therefore doing my colleagues a big favour with this: I am letting their silence help me rather than hurt me, They mostly know that I'm not an idiot and that they are unequipped to critique my proposals in detail, but they don't like to say so. Now, they don't need to say so -- I'll gain credibility, and more with every day that passes, just from their silence.

Just so.

More Progress On Creating Brain Cells

The Australian reports on more progress - to go with the gene therapy advance reported recently - in developing replacement brain cells for those lost to neurodegenerative conditions: "Neurosurgeons withdrew the stem cells from the brains of adults during routine surgery ... As long as an agent was present to induce cell division, the extracted stem cells created new and working brain cells. ... So far we have managed to produce several millions of new cells from the original stem cells. About 25 percent of them are (active) neurons. ... Researchers have long attempted to find ways of replacing dead brain cells with healthy ones in order to reverse the tragic effects of such diseases as Alzheimer's, Parkinson's and multiple sclerosis, in which the brain slowly dies."

Link: http://www.theaustralian.news.com.au/printpage/0,5942,16074134,00.html

New Eggs From Bone Marrow

The Times reports on a fascinating discovery: "Scientists have discovered that bone marrow produces primitive cells that can be summoned by the ovaries to replenish their egg supplies, challenging the theory that women are born with their life's supply of eggs. A study using female mice indicated that it may be possible to exploit this natural process in women who are infertile because of their age or cancer treatment. ... We may be ushering in a new era in the clinical management of female infertility and menopause. This could lead to new treatment approaches, based not on drugs but on regenerative medicine through adult stem cells."

Link: http://www.timesonline.co.uk/article/0,,2-1712652,00.html

Technology Review Announces SENS Challenge

The frustration of Jason Pontin, editor of the MIT Technology Review, over the inexplicable reluctance of A-list bioscientists to deliver a good scientific critique of Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS) has born fruit. From Pontin's latest post, we have the announcement of the SENS Challenge:

The most widely read story in Technology Review in 2005 was "Do You Want to Live Forever?," a profile of Dr. Aubrey de Grey, a British theoretical biologist and computer scientist at the University of Cambridge's Department of Genetics.

De Grey believes that aging, like a disease, can in principle be treated and defeated. He proposes approaching aging as a problem in engineering through something he calls "Strategies for Engineered Negligible Senescence." SENS claims to identify the 7 causes of human aging and describes how each cause might be circumvented. De Grey is also the guiding genius behind The Methuselah Foundation, an organization which offers monetary awards to biologists who make significant advances towards reversing aging in mice.

...

In my reply to our readers, whilst conceding nothing, I promised to find a working biogerontologist who would take on de Grey's ideas. But while a number of biologists have criticized SENS to me privately, none have been willing to do so in public.

This silence is puzzling (de Grey, less charitably, calls it "catatonia"). If de Grey is so wrong, why won't any biogerontologists say why he is wrong? If he is totally nuts, it shouldn't be so hard to explain the faults in his science, surely?

One possible explanation for the silence of biogerontologists is that criticizing SENS would require time and effort - and that working scientists are too busy to waste time on something so silly. Another explanation (one obviously preferred by de Grey) is that biogerontologists reject SENS out of hand without examining its details.

Technology Review thinks it would be useful to determine which of the two explanations is correct. If SENS has some validity, then we should take it seriously. Because if we can significantly extend healthy life, we will have to ask - should we?

Regardless of which explanation is correct, biogerontologists apparently need an incentive to consider SENS. To that end, Technology Review is announcing a prize for any molecular biologist working in the field of aging who is willing to take up the challenge: submit an intellectually serious argument that SENS is so wrong that it is unworthy of learned debate, and you will be paid $20,000 if it convinces independent referees. In the case that even $20,000 is insufficient to motivate the relevant experts, we also invite contributions to the fund; anyone wishing to pledge should contact me.

Pontin is not pro-life-extension, needless to say - and, sadly, still appears to be willing to describe Aubrey de Grey as "nuts." I don't agree with a number of his opinions on the workings and nature of science, even if he clearly understands where he should be going with respect to the circulation of his magazine. However, if the Technology Review staff pull this off, or even generate significant additional publicity for serious attempts to greatly extend the healthy human life span, I might just be willing to forgive some of their past transgressions.

Go and read the full post for the terms of the SENS Challenge. You might also find Aubrey de Grey's "The Curious Case of the Catatonic Biogerontologists" to be well worth reading in the present context.

More Than Just SIR2

Understanding the genetic and biochemical mechanisms of metabolism is much akin to organising a nest of paper clips - find a loose one and keep tugging to see what it's attached to. From Newswise, the latest on research into the roots of calorie restriction and its effects on longevity: "Mice, rats, worms, flies, and yeast all live longer on a low-calorie diet, which also seems to protect mammals against cancer and other aging-related diseases. A gene called SIR2 is thought to control this process. ... Triggered by low salt, heat, or extreme calorie restriction, a yeast 'master longevity regulator' called PNC1 stimulated SIR2 activity. This new work [demonstrates] that PNC1 regulates the whole SIR2 family of genes, suggesting that a human PNC1 gene might protect against diseases of aging such as cancer, heart disease and diabetes."

Link: http://www.newswise.com/articles/view/513457/

New Thoughts On Alzheimer's

Medical News Today reports on new research into the mechanisms by which Alzheimer's causes damage. Scientists "have shown that 'the plaques' which form in the brain of patients are linked to damage to nearby blood vessels. Leakage appears to occur between the blood vessels and the brain, as a result of which the plaques develop and the disease manifests itself. ... Under normal circumstances, the blood vessels transport the excess amyloid protein away from the brain. However, the protein has a harmful effect on blood vessel walls. This effect is perhaps strengthened as a result of ageing, which causes the protein to be removed less efficiently. The blood vessel loses strength and in its immediate vicinity the accumulation of the amyloid increases and plaques develop."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=28218

Comments From Aging Researchers

A nice set of comments on current aging research are lined up at ScienceWeek for your reading pleasure. Richard Miller's points are interesting:

Is it safe to conclude that oxygen molecules are the true culprits in causing aging? Can we now turn our attention to the secondary questions of how they cause physiological decline in the superannuated? There are still some grounds for skepticism. The search for antioxidant drugs that slow aging and extend life span in mammals has produced much frustration and an absence of authentic anti-aging pills.

...

Mice can live reasonably long and healthy lives despite unusually high levels of oxidative damage ... Mutations that extend worm longevity also typically lead to, and perhaps act through, increased resistance to multiple forms of stress. Thus, it seems plausible that many age-retarding mutations may work by inducing cellular signaling pathways, still poorly defined, that augment defenses against a multitude of insults, including the oxidative ones.

While it's true that scientists would seem to have nailed down all the major root causes of age-related damage, there is a way to go yet in understanding how genetic and biochemical changes influence aging. Yet our lack of knowledge regarding specific mechanisms doesn't have to hold us back from developing medical technologies capable of repairing the age-related damage we understand. You don't have to be a meterologist to fix the guttering after a rainstorm - or to build a better gutter that will withstand the next storm. So less conservatism and more research into real anti-aging therapies!

The Future Of Stem Cell Medicine

What is the logical endpoint for stem cell medicine as a mature field in 2030 or 2050? This EMBO Reports paper takes a look: "Doctors thawed a frozen tube of Jon's personalized stem cells - established in 2013 from embryonic stem cells created through somatic nuclear transfer - and injected them ... Thanks to a sophisticated cocktail of growth factors, the new stem cells target the damaged area and rapidly get to work, perfectly rebuilding a youthful heart. Several weeks later, Jon is discharged in excellent health. Regenerative medicine provided him with a new kidney ten years ago, and subsequent double knee regeneration gave him renewed mobility. Now his new heart will soon have him running a six-minute mile again. Jon Sigurdsson is 100 years old."

Link: http://www.nature.com/embor/journal/v6/n1s/full/7400427.html

Bruce Ames On Tuning Metabolism

Here we have a new EMBO Reports article for those interested in supplements and optimising metabolism using presently available techniques - a topic I think garners far too much time and attention in the healthy life extension community. You can spend as much time and money as you like trying to keep up with ever-changing science, but will you ever really know if you are succeeding? This isn't like tinkering on a car engine, where the output is clearly understood and easily measured; in the absence of biomarkers for aging, you'll never know if you're getting good value for money. Take care of the health and longevity basics, but I suspect that further resources are best directed towards supporting the future of real anti-aging medicine and meaningful longevity research.

Link: http://www.nature.com/embor/journal/v6/n1s/full/7400426.html

Bone On Demand

The BBC delivers more good news on the bone regeneration front: "We have shown that we can grow predictable volumes of bone on demand. And we did so by persuading the body to do what it already knows how to do. ... The technique uses the body's own natural wound-healing response, which allows broken and fractured bones to knit together, by creating a space around the healthy bone and encouraging growth." This is a clever technique, but still unproven in humans as the article points out. Still, it is promising to see so many different tactics in present day bone regeneration research. That is a good sign for the future, especially for those suffering from the age-related bone loss of osteoporosis.

Link: http://news.bbc.co.uk/2/hi/health/4714781.stm

Nanoparticles For Gene Therapy

A step forward for gene therapy is reported at Newswise: "Using customized nanoparticles that they developed, University at Buffalo scientists have for the first time delivered genes into the brains of living mice with an efficiency that is similar to, or better than, viral vectors and with no observable toxic effect ... scientists used gene-nanoparticle complexes to activate adult brain stem/progenitor cells in vivo, demonstrating that it may be possible to 'turn on' these otherwise idle cells as effective replacements for those destroyed by neurodegenerative diseases, such as Parkinson's." A most interesting twist on current work into gene therapy and regenerative medicine through the manipulation of adult stem cells.

Link: http://www.newswise.com/articles/view/513306/

First Generation Adult Stem Cell Heart Therapies

For the past couple of years, various modes of first generation adult stem cell therapy for heart disease have been trialed - mostly outside the US prior to 2004, thanks to the heavy, unaccountable, keep-my-own-job-safe hand of the FDA. These are comparatively simple therapies; forms of transplant using either donor stem cells, usually from bone marrow, or cultured stem cells from the patient to avoid immune rejection. An update on one of the latest trials:

Two patients have already been enrolled at Hopkins in a Phase I clinical trial, which is designed to test the safety of injecting adult stem cells at varying doses in patients who have recently suffered a heart attack. In total, 48 patients will participate in this study, which is happening at several sites across the country. Results are not expected until mid-2006.

...

The researchers are using a special kind of stem cell in an early stage of development, called adult mesenchymal stem cells, to avoid potential problems with immunosuppression, in which every human's immune system might attack stem cells from sources other than itself.

This trial uses cells from sources other than the patient, and performed very well in animal studies. If regulatory matters and commercialization proceed at the normal pace for the US medical system, some form of effective stem cell therapy for heart disease should be a widely available option by 2010.

Revisiting the Other Half of the Fight Against Chronic Disease

It seems evident that much of the gain in healthy life span over the past hundred years is the result of a large reduction in chronic disease - less disease means less acculumated damage to the complex machinery of your body, which leads to a better chance at a longer life, at least according to the Reliability Theory of aging. It is also established that at least a few age-related conditions are caused by or aggravated by forms of chronic infection. The latest article from SAGE Crossroads takes a look at this topic:

Since the discovery of Alzheimer's disease (AD) a century ago, researchers have probed many possible causes for the brain-ravaging illness, from nutrient deficiencies to the aluminum in cooking pans. But if an unorthodox hypothesis proves correct, the cause of AD was right under our noses all the time - or even inside them. According to a growing band of scientists, many of old age's scourges - including atherosclerosis, AD, and some cancers - stem from infections by bacteria and viruses. The evidence so far is inconclusive, but if research confirms the contention, doctors might be able to use the arsenal of antimicrobial weapons to prevent or even treat some of the most dreaded illnesses of old age.

Calls for greater government intervention aside (no surprise considering the source), it's clear that much more work needs to be done to conclusively link common age-related conditions to infectious agents. It is an attractive idea, as identifying a problem species of bacteria or virus would open the door to new and effective prevention strategies. The attraction doesn't mean these theories are necessarily right in the cases we'd like them to be, however. More research would seem to be justified, but bear in mind my earlier comments:

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

Fishing For Longevity Genes

From PLoS Genetics, the results of a search for more genes affecting longevity in nematode worms. Researchers have "identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. ... Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias." This study should contribute to the scientific understanding of calorie restriction and other metabolic tweaks that can extend healthy life span. While unlikely to lead to radical life extension, increasing longevity by improving metabolism is plausible for the near future of medical science.

Link: http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pgen.0010017

Development Causes Aging?

From the desk of aging researcher Joao Pedro de Magalhaes: "The idea that development is linked to aging has been frowned upon by scientists for decades, but new evidence demonstrates the two are not only linked but that aging and development are regulated by the same genetic mechanisms. ... Even in mammals there is growing evidence that aging is a consequence of developmental mechanisms. For instance, the pace of development influences the pace of aging, suggesting that the timing of developmental mechanisms determines the timing of aging in mammals. ... While the same genes drive development and aging, the researchers do not
consider that aging is an intentional product of evolution like development."

Link: http://genomics.senescence.info/news/072505.html

Stress Response And Life Span

AScribe reports on results from one of the first experiments making use of automated methods of sorting and analysing large numbers of nematode worms. "University of Colorado at Boulder scientists have used a fluorescent marker to predict the individual life spans of identical worms that were genetically engineered to illuminate stress levels, implying living organisms have 'hidden physiological states' that dictate their ability to deal with the rigors of life. ... We have shown it's possible to predict the life span in an organism on the first day of adult life based on how it responds to stress. ... Carried out using about 100,000 popular laboratory nematodes known as C. elegans, the study indicated the brightness level triggered by the reporter protein could predict up to a four-fold variation in the life expectancy of a worm."

Link: http://newswire.ascribe.org/cgi-bin/behold.pl?ascribeid=20050722.084254

ACT On SCNT-Based Therapies

(From the Life Extension Foundation News). Advanced Cell Technology (ACT) is back to work on therapeutic cloning (also known as somatic cell nuclear transfer, or SCNT) to repair age-damaged immune systems: "These cloned stem cells appear to have a powerful regenerative capacity ... The ability to regenerate an aged or defective immune system without the need for drugs, tissue matching, or the risk of graft-versus-host disease would have important implications for medicine. We hope to use this technology in the future to treat patients with diverse diseases such as marrow failure disorders, various genetic diseases and malignancies, as well as debilitating autoimmune diseases, including MS, arthritis, diabetes, and lupus."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2487

Head Out of Shell, Aware, Moving, But Not in the Right Direction Yet

If you want to take the long term view, articles like this one from the BBC are at least modestly promising. People are slowly opening their eyes and talking about aging in a more positive way, as something that can be changed and improved upon. Recognizing that there is an issue - that degenerative aging is extremely unpleasant for everyone who suffers and eventually dies from it - and that sufficient investment in science can make a difference is the first step.

Rising life expectancy could mean older people having to endure more years of ill health at the end of their lives, say peers. A House of Lords Science and Technology Committee report says more must be done to make older people healthier and to improve their quality of life. It calls on the government to apply scientific resources to improve health in old age.

We advocates must continue in our work to promote serious, scientific anti-aging research to those who have finally come to the conclusion that aging is not immutable, and that scientific research to ameliorate age-related suffering and ill-health is a good idea.

(I'll pragmatically refrain from commenting on the knee-jerk British reaction to address matters, especially matters medical, through horribly inefficient and unaccountable government programs).

Which Individuals of Great Personal Wealth To Pitch?

The healthy life extension community has certainly grown and become more mainstream over the past five years. This is all to the good, especially when the concepts of radical life extension and the prospects for research to achieve it are becoming more widely understood, both inside and beyond the scientific community. As Gandhi famously said, "First they ignore you, then they laugh at you, then they fight you, then you win." On this scale, we're doing pretty well - scientifically literate folks aren't laughing any more, and the laughter fades from other segments of the population as media coverage spreads. Instead, we see a battle of ideas between those opposed to the very idea of healthy life extension, scientists arguing over timescales, funding and possibilities, and advocates for longer, healthier lives telling them to get on with it.

One common form of advocacy movement can be thought of as a pyramid; a large number of supporters and hard workers support a few people who are deliberately placed to catch and focus media and public attention. We humans have brains designed for village life - we like to relate to individuals rather than organizations or causes, and organizations providing individuals for that purpose tend to outperform. The apex of one of the pyramids I am involved in is biomedical gerontologist Aubrey de Grey, author of the Strategies for Engineered Negligible Senescence (which I'm sure comes as no surprise to regular readers). By acting as a focal point for a portion of the healthy life extension community, Aubrey finds doors are opened that would otherwise be shut. Media coverage, organizational support and a network of supportive contacts are required in order to generate more of the same - in much the same way that the easiest way to make money is to start with a pile of money. It's a positive feedback look - growth and success inspires more growth and success. Every avalanche starts with a pebble, but it's a great deal of hard work to get the first few hundred pebbles to see it your way. After that, the options become more interesting.

Aubrey de Grey, and by extension the rest of us, are seeing new opportunities on the horizon. Invitations to self-important global conferences beyond the scientific community (such as TED) are a currency that can be grown and eventually bartered into relationships with wealthy philanthropists ... and thus funding. Give it a couple of years at the present rate of growth (of the Mprize for anti-aging research, of media coverage of SENS, of the supporting community, of connections to the wealthy and influential) and Aubrey will be pitching billionaires.

Which billionaires should Aubrey de Grey be pitching for funding for his proposed Insitute of Biomedical Gerontology, or for a series of research prizes focused of repairing the biomolecular damage caused by aging? Or rather, at this stage, which billionaires should Aubrey and his supporters be considering for cultivation? We know that John Sperling and Larry Ellison have a strong interest in aging and longevity research, and have already devoted large sums of money to the cause. Does this make them better or worse candidates? The executive director of the Ellison Foundation is a skeptic when it comes to SENS, for example. While it would no doubt be possible to pitch Ellison directly in years ahead, it may not be as fruitful as pitching another billionaire who has not spent years forming an existing set of opinions on the topic.

Have thoughts on the matter? Comment away...

What The Politicians Are Up To, Part II

For those keeping tabs on US federal stem cell politics, an update from the New York Times: "A measure to expand federal financing for human embryonic stem cell research, passed by the House and once considered a shoo-in for adoption by the Senate, is tangled up in a procedural dispute that will probably delay a vote until fall - and could wind up killing the bill." Some pointers on how to have your say in this matter can be found here at the Longevity Meme. To my mind, research would be moving much more rapidly in a world without governments able to interfere in every aspect of life - sadly, we do not live in that world. Thus we are beset with endless battles and resources wasted in struggles over power and control.

Link: http://www.nytimes.com/2005/07/23/politics/23stem.html

FuturePundit On Mitochondrial Research

Randall Parker offers his thoughts on recent research into mitochondria and aging over at FuturePundit. He notes that "Prolla thinks an obvious next step would be to genetically engineer mice to have a lower rate of accumulation of mitochondrial DNA mutation." This is good - showing that increased damage reduces life span is only half the battle. There are plenty of line items that can reduce life span but have no real connection to aging; the conclusive proof would be to demonstrate that lower mutation rates increase life span. Then, "we can begin to think about pharmaceutical interventions to retard aging by preserving mitochondrial function. ... Hopefully Prolla's report will be seen by the scientific community as a reason to do the work necessary to genetically engineer mitochondrial genes to move them into the nucleus."

Link: http://www.futurepundit.com/archives/002910.html

One For the Actuaries in the Audience

From aging researcher Leonid Gavrilov, a pointer to a collection of articles on aging and longevity from the perspective of the Society of Actuaries. As a few minutes browsing will lead you to note, the present day process of determining mortality rates and statistics of aging is anything but easy or cut and dried. You might find the following PDF-format papers from the collection interesting:

The Great Debate on the Outlook for Human Longevity:

Several leading gerontologists are engaged in a spirited and even vituperous debate regarding the prospects for human longevity. The issue is what life expectancy will be just after mid-century in the industrialized countries, and, more particularly, in the United States in 2060. The debate on the future of life expectancy is closely linked to such issues as the possibilities for extending average recorded human life span, the existence of limits to human life span and life expectancy, the form of the trajectory of age-specific mortality rates at the highest ages of life and the utility of developing projections of mortality on the basis of causes of death

Search for Predictors of Exceptional Human Longevity:

Centenarians (people living to 100 and beyond) represent the fastest growing age group of the American population, with obvious implications for actuarial science and practice. Yet, factors predicting exceptional longevity and its time trends remain to be fully understood.

Actuarial circles seem fairly conservative with respect to healthy life extension, rather like a large portion of the gerontology community. If this selection of articles is any guide, most actuaries regard it as somewhat radical to suggest that current trends in human longevity may continue, never mind greatly accelerate due to funding of serious anti-aging medicine.

Fishing For Alzheimer's Drugs

While scientists use the tools of modern biotechnology to uncover the mechanisms of Alzheimer's disease, another path forward lies in low-cost mass analysis of potential drugs. Bioinformatics and new tools have made the process of screening potential compounds comparatively cheap - and the cost is still falling. Here, EurekAlert reports that a "team of scientists has discovered three molecules - from a search of 58,000 compounds - that appear to inhibit a key perpetrator of Alzheimer's disease.
Each of the three molecules protects the protein called 'tau,' which becomes hopelessly tangled in the brains of patients with Alzheimer's. The finding is promising news for the development of drugs for the disease." You may recall recent promising work on tau and neurofibrillary tangles in Alzheimer's.

Link: http://www.eurekalert.org/pub_releases/2005-07/uoc--sdt072005.php

Searching For Heart Stem Cells

From EurekAlert, a good example of investigative work by scientists seeking to understand the basis of healing and regeneration. Researcher Steven Houser "is sold on the idea that the heart - like the skin - contains its own stem cells: cells that are self-renewing and can be differentiated into different types of heart tissue. It's a controversial subject in cardiovascular circles, but for Houser, who spent thirty years studying the molecular biology of heart cells, the stakes are worth it when it comes to combating congestive heart failure (CHF). Although stem cells have been found in many other organs in the body, including the brain, many researchers remain unconvinced that the heart contains stem cells. Houser respectfully disagrees."

Link: http://www.eurekalert.org/pub_releases/2005-07/tu-alf071505.php

On Those Stem Cell "Alternatives"

Chemical & Engineering News looks at the various proposed "alternatives" to embryonic stem cell research. While the scientists at work are usually sincere in their exploration of stem cell biology, the politicians and groups pushing this research are invariably opposed to embryonic research on all the usual grounds - same old story, different day. "These so-called 'alternatives' are not true alternatives, as they currently represent only speculative proposals for research that might yield new stem cell lines and are fraught with their own ethical problems ... a bill that supports these alternatives instead of an expanded federal policy is 'a vote to delay biomedical research.'" Embryonic stem cell research is a necessary, important part of modern medical science - and freedom of research is vital.

Link: http://pubs.acs.org/cen/news/83/i30/8330earlygov2.html

Thinking About A Fifty-Year Cycle

From Genetic Engineering News, thoughts on the nature of fifty-year business cycles and where biotech is heading: "Combining the rapid advances currently being made in cell biology with genomics, proteomics, and nanotechnology, it may be possible, over the next decade, that scientists will be able to create and engineer artificial cells for generating new tissues, limbs, and organs. It may also be conceivable by 2030, when the biotechnology revolution reaches the end of its 50-year cycle, that the average life span of humans will reach 125 years, which would translate into todays 35-year-old adults being the equivalent of tomorrows 70-year-old adults. It may be a fact or just plain science fiction. Only time will tell."

Link: http://www.genengnews.com/current/article.aspx?cat=Wall%20$treet%20BioBeat&id=69

GDNF in the News

An interesting press release via the GRG list discusses a new way of producing glial-derived neurotrophic factor, or GDNF:

GDNF has been shown to protect dopaminergic brain cells, neurons that produce dopamine that becomes depleted in Parkinson's patients. GDNF has also been shown to have a beneficial role in protecting neurons in animal models of Amyotrophic Lateral Sclerosis (ALS) and Spinal Cord Injury (SCI).

Most of the current treatment of neurodegenerative diseases provide limited benefit to patients. Drugs for Parkinson's disease, which focus on dopamine supplementation, often cause prohibitive side effects. To overcome these problems, researchers around the world are intensively exploring novel cell- and gene-based therapies for replacement and augmentation of the lost neurons. Prominent among these novel therapies are attempts to deliver GDNF to the site of neuronal regeneration.

In the current BrainStorm-sponsored study at Tel Aviv University, biochemical and immunological methodology showed that human bone marrow mesenchymal stem cells may be uniquely differentiated into cells that resemble astrocytes, express astrocytic markers and produce significant levels of GDNF.

...

"Neurologists have long thought that GDNF can be used to preserve and maintain the integrity of dopaminergic neurons in Parkinson's disease. However, delivery to the appropriate location is a major challenge. Direct delivery of the protein has failed and there are current ongoing attempts at gene therapy. We believe that our approach, based on neural transplantation of stem cell derived GDNF producing cells, without any genetic manipulation, is preferable," said Prof. Eldad Melamed, Chairman of the Scientific Advisory Board.

In addition, "The use of a patient's own bone marrow stem cells to generate neural cells for replacement and support of a patient's damaged dopaminergic cells is a strategy that will avoid problems of immunological rejection," said Dr. Daniel Offen, Chief Scientist.

Make of that what you will; the good news I take away is that a variety of methods for attacking this class of neurodegenerative disease are currently under investigation. Diversity of study is always promising in the long term, and any progress towards curing or preventing neurodegeneration is a good thing. In the near future, probably within 10 years, you'll be able to replace failing organs with engineered tissue should your personal worst case medical scenario come to pass - but age-related damage to the brain has to be repaired in situ. Hence those of us interested in healthy life extension should also be interested in neuroregenerative work.

Merck, Geron To Collaborate

In business news today from SFGate, Merck and Geron announced their collaboration on research into telomerase-based cancer therapies. Telomere science, like stem cell science, is a field in which any progress lends aid to aging and serious anti-aging research - these fields all overlap in their examination of cellular mechanisms, genetics and biochemistry. So prominent private funding deals are a welcome sight - they indicate that more progress is happening out of sight, and that funding organizations believe this work to be significant. "The partners plan to try both Merck's and Geron's vaccine-making methods in cancer therapies aimed at telomerase. Each will profit from whatever version works best."

Link: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2005/07/19/BUG3LDPTVQ1.DTL

Ronald Bailey On Liberation Biology

ScienceBlog is running an interview with Ronald Bailey on his latest book, Liberation Biology. "The benefits of biotechnology are well known -- the cure of diseases and disabilities for millions of sufferers; the production of more nutritious food with less damage to the natural environment; the enhancement of human physical and intellectual capacities. All of these benefits can be easily foreseen. It is the alleged dangers of biotechnology that are, in fact, ill-defined, and nebulous." The advance of biotechnology is indeed a liberation - a liberation first from sickness, then from degenerative aging, and finally from involuntary death. We are a thousand times better off than our ancestors for just the progress of the past century - and this is merely the beginning of a long, fascinating path of discovery and growth.

Link: http://www.scienceblog.com/cms/node/8480

Aubrey de Grey at TED Global

For a splashy, high-power conference on the future of technology, TED Global 2005 has certainly left very little imprint in the media. Biomedical gerontologist Aubrey de Grey was one of the speakers this year, there to talk about the Strategies for Engineered Negligible Senescence and the future of healthy life extension research. You can find a non-Macromedia program of speakers elsewhere online - Peter Diamandis, Craig Venter, Kari Stefansson and Richard Dawkins are some of the other noteworthy folks.

One can hope that Aubrey spent his time turning his considerable charisma to forging potential relationships and cultivating donors. As opposed to, say, punting, that is ... as that post notes:

The attendees, while too engrossed to write, were still able to snap away? Including this one of extropian anti-aging beard-king Aubrey De Grey on a punt!

So come on people - there have to be some attendees out there in the wider blogosphere up to writing first hand reports of the bioscience topics to go with all those photographs.

SIRT1 Further Examined

You may recall that SIRT1 is a major player in the mechanisms by which calorie restriction extends healthy life span. However, as reported at EurekAlert, "we showed that, unlike in yeast, mouse SIRT1 can function to suppress cellular longevity rather than to promote it. That has been a big surprise to the field since it does not fit with preconceived notions of the role of SIRT1 ... SIRT1 affects a particular response pathway to DNA-damaging oxidation. They found that SIRT1-deficient cells, in contrast to normal cells, continued to divide when treated chronically with low-level doses of oxidation-inducing hydrogen peroxide. However, the SIRT1-deficient cells had a normal senescence response when exposed to high-level oxidation or the activated cancer gene, Ras. Together, these results indicate that SIRT1 has a specific role in the response to chronic oxidative damage." More research is called for.

Link: http://www.eurekalert.org/pub_releases/2005-07/hhmi-rig071905.php

Kurzweil Charity Auction Raises $8000

(Via KurzweilAI). The Mprize charity auction for lunch with futurist and healthy life extension advocate Ray Kurzweil ended on a high note last week: "Doug Arends of Ottawa, Ontario, Canada, bidding for a group of Mprize (Methuselah Mouse Prize) supporters, placed the winning bid in an eBay auction for lunch with Dr. Ray Kurzweil, author of the best-seller Fantastic Voyage: Live Long Enough to Live Forever. The winning bid came in at US $4,050.00. Dr. Kurzweil himself surprised Mprize supporters by offering a $4000 matching grant, nearly doubling the winning bid and bringing the Mprize fund up to over $1,460,000." The larger the fund, the more it will encourage scientists to work towards technologies of healthy life extension.

Link: http://www.kurzweilai.net/news/frame.html?main=/news/news_single.html?id%3D4672

Evolution And Aging

The latest SAGE Crossroads article examines the evolution of evolutionary theories of aging: "The leading evolutionary explanation for aging has reached its silver years. Born in the late 1940s, the theory matured in the 1960s and flourished in the following decades, as researchers amassed evidence supporting its predictions. But like many of its contemporaries, the theory now needs to have a little work done. Evolution experts don't envision a makeover, merely a few nips and tucks to explain some vexing results from field studies and mathematical models." Evolutionary theories of aging help to direct research into the biochemical and genetic mechanisms of aging; like the Reliability Theory of aging, they provide a framework and testbed for more detail-oriented theories and examinations.

Link: http://www.sagecrossroads.net/Default.aspx?TabID=28&newsType=ArticleView&articleId=124

From Mitochondria to Orange Juice

A great example of the need for caution and careful reading when following science in even the more reputable mainstream media can be found at the BBC. You might recall the buzz over recent work on mitochondria and aging that implies free radical damage is not as important a mechanism of aging as thought. The folks on the Gerontology Research Group list have suggested a wait and see approach - much the same as the line taken by Aubrey de Grey in this piece:

Dr Aubrey de Grey, an expert in ageing research at the University of Cambridge, said: "This is an important study, building on similar work by a couple of other groups over the past few years.

"It would be premature to say that these studies are conclusive with regard to the role of mitochondrial mutations in ageing, but they certainly imply that cell death, especially of stem cells, can make a big difference to the rate of ageing."

He said it was important to be cautious because it was impossible to be sure that something which shortens life if you accelerate it is also lifespan-limiting when it proceeds at its natural rate.

"Ideally, we would develop mice that had better mitochondrial DNA repair and maintenance and lived longer as a result, but we don't have that result yet."

The attention-grabbing header of the article - involving large quantities of orange juice, antioxidants and the dispelling of dearly held theories - is somewhat sensationalist, even if it may not appear as such to the casual reader.

Tom Kirkwood On Aging

Another EMBO Reports paper for your reading pleasure today: "One of the greatest scientific mysteries, which has puzzled scientists for thousands of years, is what controls the length of life. At a time when human lifespan is increasing to previously unforeseen lengths, it is urgent that this ancient question is answered. Fortunately, recent progress suggests that the answers will soon be at hand. ... demographic trends over the past 2-3 decades have shown that, instead of reaching a plateau as most forecasters had predicted, human life expectancy has continued to increase and shows no sign of slowing. This has taken everyone by surprise, because the conventional view of ageing is that maximum life expectancy is somehow 'fixed'."

Link: http://www.nature.com/embor/journal/v6/n1s/full/7400419.html

The Front Lines Of Cancer Research

The cutting edge of cancer research today looks very different from the work performed a decade ago. Scientists strive to understand the biochemistry and genetics of the cellular life cycle, as cancer results from failures in these mechanisms. It is an added bonus that this research will greatly benefit attempts to halt or reverse the aging process. From Medical News Today: "This is one of the few genes that has been discovered that directly controls two pathways, cell proliferation and cell apoptosis, or cell death. Sustained growth of cancer cells requires activation of the cell proliferation machinery and suppression of a system called the apoptotic failsafe mechanism. The combination of suppressed cell death and deregulated cell production is likely a key element in cancer."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=27541

Kurzweil Auction Wrapup

The dust has settled from the Methuselah Foundation charity auction for lunch with futurist and healthy life extension advocate Ray Kurzweil; congratulations to the lucky winner. I think that we can call it a win all round despite the uphill battle on the publicity side ... and we won't talk about just how long it took the combined technical genius of the Mprize volunteer crew, myself included, to figure out the details of how to run charity auctions on eBay through MissionFish. A humbling experience indeed. From Jay Fox:

The first main area of success was, of course, the money. The winning bid was $4,050.00, and when combined with Ray Kurzweil's generous offer to match up to $4,000.00, the total cash benefit to the prize was $8,050.00. When added to the cash already collected for the prizes, this would bring the total cash collected to nearly $160,000.00.

The second main area of success was public awareness and outreach. This multi-faceted area of success includes a doubling or more of the number of pages that link to the MPrize, a spike in traffic to the website, and at least one new membership to The Three Hundred, a group of dedicated individuals and organizations which pledge $1,000 a year for 25 years. These $25,000 commitments will help fund the first skirmishes in the coming War on Aging.

Please take a moment to recognize that a great deal of hard work goes into these fundraising events - the ongoing growth and success of the Mprize for anti-aging research is due to the commitment and dedication of volunteers and donors alike.

You can show your support for the fight to cure aging by donating to the Mprize fund. The amount doesn't matter; it is more important that you stand up and make a statement about your desire for the future - to enter a world of longer, healthier lives and working longevity medicine.

Update On Myostatin And Mighty Mice

(From Medical News Today). You may recall that scientists demonstrated impressive muscle growth in genetically engineered mice that lacked the growth regulator myostatin. The same team has now shown that "it's possible to get the same effect by blocking the gene for myostatin, rather than entirely knocking it out. ... Until now, it's been purely theoretical that we could block the gene and obtain the same muscle-building effect as deleting the gene." This makes therapies for age-related muscle loss and wasting diseases much more plausible in the years ahead, although "for human applications, this research is just the beginning."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=27544

Banish This Phrase

Medical News Today notes that the gerontological powers that be have decided that yet another age-related degeneration from good health is not "a normal part of aging." Personally, I think that we should banish this phrase from our lexicon, and the sooner the better. Why accept any form of age-related degeneration as inevitable or "normal"? We live in an age of dynamic science, at the very beginning of an increasingly rapid revolution in medicine and biotechnology. If you don't want to lose your health as you age, then speak up! Scientific research will ultimately allow us to sever the present connection between age and ill health, but only if large scale funding and widespread public support starts now.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=27445

How Old Are Your Cells?

The replacement rate of cells in our body varies greatly between different types of cell, but up until now scientists couldn't make precise estimates. Nature reports the latest results: "Samples taken from the visual cortex, the region of the brain responsible for processing sight, were as old as the subjects themselves, supporting the idea that these cells do not regenerate. ... Other brain cells are more short-lived ... In an average person of some 30 years of age, intestinal cells are about a decade old and skeletal cells a bit older than that. Cells that endure a great deal of physical stress, such as red blood cells, are known to turn over every few months. The research team believes that dating cells using carbon-14 will shed light on the role of cell death in cognitive disorders."

Link: http://www.nature.com/news/2005/050711/full/050711-12.html

Talking to Bruce Ames of Juvenon

ScienceDaily has a two part interview with Bruce Ames (part one, part two) of Juvenon - another portion of the wider healthy life extension community that sells old school products while discussing new school science. (A skeptic would say "hyping supplement sales with talk of mitochondria"). I would lump them into the same category as A4M or the Life Extension Foundation; heart in the right place, but basically health concerns rather than longevity concerns in all but rhetoric.

I have nothing against supplements: I use them, they're demonstrably good for your health in both the short and long term, but they are not the future of healthy life extension. Taking care of your health today is of course something you should do, but a focus on supplements to the exclusion of supporting research into developing working rejuvenation medicine is the path to aging and death - see some of my previous comments on this matter for a sense of where I stand on it all. Sadly, all too many people don't realize that there is anything beyond the very large, very vocal "anti-aging" marketplace as it stands today.

If you're big on mitochondria, selling vitamin supplements is not the way to support the future of healthy life extension. There are more than enough people out there selling vitamins; many of them are even responsible and do a good job. Protofection research and work on understanding the modes of mitochondrial damage and its cause and effect - now that's the way to go.

Science & Theology News Peers at Liberation Biology

Liberation Biology by Ronald Bailey is of course worthy of note, but I thought I'd point out this review from Science & Theology News:

Bailey addresses major issues in biotechnology: longevity, disease control, stem cell research, cloning, designer babies, agricultural biotechnology and mind improvement drugs.

Bailey openly dismisses bioconservative arguments, saying their "fears are vastly exaggerated; their ethical objections to biotechnological progress are largely misconceived; and the biotech revolution rather than diminishing human dignity and liberty will instead enhance and enlarge them." He takes leading bioconservatives to task, writing that the "future toward which the biotech revolution is taking humanity is in fact almost the exact opposite of the Brave New World."

The advance of biotechnology is indeed a liberation - a liberation first from sickness, then from degenerative aging, and finally from involuntary death. We are a thousand times better off than our ancestors for just the progress of the past century - and this is merely the beginning of a long, fascinating path of discovery and growth. More and better is to come, and those who oppose better medicine and longer, healthier lives should be denounced for the selfish fools they are.

News From Suspended Animation

It's been a while since we've heard anything from cryonics company Suspended Animation. From the Tallahassee Democrat, in an otherwise unsympathetic article: "Suspended Animation expects to open in August. The facility was approved 4-1 by Boynton Beach commissioners in March, after being repeatedly rejected by Boca Raton officials. ... The South Florida lab will primarily act as a processing facility to freeze dead bodies, Platt said. It will not store bodies. Alcor is negotiating with Suspended Animation to receive bodies. The companies share a board member, Saul Kent [of the Life Extension Foundation], also with South Florida ties." Learn more about the science and practice of cryonics here at the Longevity Meme or at the excellent Alcor website.

Link: http://www.tallahassee.com/mld/tallahassee/news/breaking_news/12141320.htm

Mitochondria, Aging Research Again

(From EurekAlert). Mitochondria are a hot topic in aging research these days. "Growing old, according to the new study, occurs, in part, as mutations build up in the DNA of energy-generating mitochondria, triggering the death of critical cells that lead to such things as hair and weight loss, hearing and vision impairment, loss of muscle mass, weakened bones and fewer circulating red blood cells. ... We think that the key to what is happening in aging is that as (genetic) mutations or DNA damage accumulates, critical cells die. These experiments favor a major role for programmed cell death in aging." Keep an eye on mitochondrial research - it offers intriguing possibilities for healthy life extension medicine over the next decade.

Link: http://www.eurekalert.org/pub_releases/2005-07/uow-emy071105.php

Alzheimer's: Tau, Tangles or What?

Researchers see Alzheimer's as a two-protein disease: amyloid plaque - target of attempts to produce an Alzheimer's vaccine - on the one hand and neurofibrillary tangles on the other, both somehow related to or responsible for neurodegeneration. One particularly interesting thread of Alzheimer's research involves exploring the theory that these neurofibrillary tangles are not in fact a root cause of mental degeneration associated with the disease. You can find a high level overview of the basics over at Nature:

The brains of people with Alzheimer's and some 50 other forms of dementia are known to have certain characteristic features, including messy bundles of fibres in nerve cells called neurofibrillary tangles. But no one has been sure whether the tangles are a cause or symptom of dementia.

Mice engineered to massively overproduce a protein called tau tend to grow more of the tangles and display the same problems with memory and learning as humans with dementia. Researchers think that it is a certain version of the tau protein, rather than a simple over-abundance, that leads to the tangles.

It has been speculated that these tau proteins, rather than the tangles, kill nerve cells.

...

They trained mice to navigate a maze partly submerged in water, and watched for signs of memory loss. By the age of three months, mice genetically engineered to express 13 times too much tau protein couldn't remember the route to dry land, and had developed tangles in their brains.

But surprisingly, when the researchers turned off the switch promoting tau expression, the mice began to gain back some lost memory.

Most promising. Progress towards understanding and defeating the most common neurodegenerative diseases is a vital part of healthy life extension science. After all, the worst case scenario for the future of your heart and other organs is that they will have to be replaced wholesale with new, healthy tissue grown from your own cells. This isn't an option for the brain - so we had better develop very effective means of in situ repair.

More Mitochondria, Aging Research

EurekAlert reports on the work of Prolla and Kujoth, who find "that accumulation of mitochondrial mutations that promote apoptosis, or programmed cell death, may be a central mechanism driving aging and may be unrelated to the release of free radicals, previously thought to cause aging. ... By breeding mice with the inability to detect and repair mistakes in the DNA replication process, researchers discovered there was no increase in oxidative stress despite an increased mutational load. However, there was a significant increase in apoptosis. ... The finding disproves the previously believed mitochondrial 'vicious cycle' theory of aging, which states that increases in mitochondrial mutations increase oxidative damage, which is one cause of aging."

Link: http://www.eurekalert.org/pub_releases/2005-07/uof-usf071405.php

Last Day of Auction, Kurzweil To Match Bids

If you and your friends would like to meet inventor, entrepreneur and healthy life extension advocate Ray Kurzweil, today is the last day of bidding on the Mprize celebrity lunch auction. All proceeds will go to encourage scientists to develop working rejuvenation therapies, and Ray Kurzweil has generously offered to match up to $4,000 of the winning bid. "The MPrize - in the spirit of the fabulously successful X Prize - is a powerful vehicle for mobilizing the scientific community to eliminate the degeneration associated with aging. In addition to my earlier donation, this is a fun way to support a cause I believe in - helping people live longer, healthier lives. I look forward to sharing an afternoon of food and conversation with others who are similarly committed."

Link: http://www.forbes.com/businesswire/feeds/businesswire/2005/07/14/businesswire20050714005473r1.html

Stem Cells Suppress Inflammation?

The results of more speculative stem cell studies are starting to show up these days - one sign of increasing funding. This is an interesting one, reported at the National MS Society: "[adult mouse neural stem cells] injected into the blood of mice with MS-like disease were able to suppress the immune attacks that damage the brain and spinal cord tissues. ... These surprising findings, if confirmed, suggest that neural stem cells that reside in the adult brain may not only serve as replacement cells for tissue repair, but in some circumstances may also protect the brain from inflammation. Further research is needed to confirm these results and to address multiple issues involved in translating such experiments into finding ways to fight the immune attack and protect and repair brain tissues."

Link: http://www.nationalmssociety.org/Research-2005July13.asp

On Death As An Unnatural Process

Kevin Perrott of HealthExtension.net annotes bioethicist Arthur Caplan's article in the latest EMBO Reports. "Why are the physiological changes and deteriorations that are associated with ageing considered to be unremarkable natural processes whereas similar debilitative changes are deemed critical diseases when they occur in younger people? Progeria - rapid ageing in a child - is considered a horrible disease, whereas the same changes occurring 80 years later are considered normal and unworthy of medical interest. ... This applies even to young adults who if they had the blood sugar response of a 'normal' 65 year old would normally be classified as diabetic. By any dictionary definition, aging qualifies as a disease with multiple pathological symptoms so why is medicine so reluctant to treat aging as a proper disease target?"

Link: http://www.healthextension.net/archives/2005/07/death_as_an_unn.html

Jay Fox on the Daily Show Tonight (Updated: ... Or Not)

I have it on good authority that Jay Fox will be - briefly - on tonight's edition of the Daily Show in a segment on "The Fountain of Youth." So respect the sacrifice in pride he is making for the wider cause of healthy life extension advocacy and tune in.

Don't forget to watch the Daily Show with John Stewart, tonight (Wed., July 13) at 11 PM EDT on Comedy Central. I've been told I will be on for about 30-45 seconds. No idea if my plug for the MPrize made it to the final cut. Anyway, have a good laugh at my expense.

We shall see if all publicity is good publicity...but join the discussion at the Immortality Institute forum and have your say on the matter.

UPDATE: Ah, the vagaries of media scheduling.

The segment on "The Fountain of Youth", in which I will appear, and which was originally scheduled to air tonight, has been rescheduled. It is tentatively scheduled for Monday, July 18th. Tentatively.

Why Embryonic Stem Cell Research?

With all the spume and nonsense online and in the media regarding embryonic stem cell research, it's actually quite hard to find a sane, well-written, scientific article that explains just why embryonic stem cell research is important. The staff over at blog.bioethics.net seem have found a good example, even if it is rather diluted by discussion of funding and politics:

My laboratory is studying embryonic stem cells in hopes of making blood stem cell transplants safer and more widely applicable. A critical part of the strategy is using somatic cell nuclear transfer to generate stem cells that are customized to the specific patients I mentioned earlier, kids with leukemia, immune deficiency, and sickle cell anemia. We hope to correct the genetic defects in these patient-specific cells, direct their differentiation into blood, and transplant kids with these genetically matched autologous cells. This strategy is already working in mice, and we are eager to translate this work into humans. The current Federal funding policies have held us back.

Although it is true that no one has to date been treated with cellular therapies based on human embryonic stem cells, I can assure you that mouse embryonic stem cells have had a major impact on medical research. Over the past 25 years, mouse embryonic stem cells have been used to create models for scores of human diseases, including cancer, heart disease, obesity, and Alzheimer's. Research discoveries based on these models has led to new drug development and therefore touched countless lives. As for the criticism that no one has been cured with embryonic stem cells, the field of human embryonic stem cell research is a mere 7 years old, so it is premature to expect successful cell therapies to have already been delivered to patients. I believe it is only a matter of time before human embryonic stem cells are used in drug development research and become the basis for important new cell therapies.

As further evidence of how human embryonic stem cells enable unique opportunities to study disease, consider research on Fanconi's anemia. Kids with Fanconi's anemia suffer bone marrow failure, and often develop leukemia. Scientists have tried to model this disease in mice, but the mice do not develop bone marrow failure, and the adult blood stem cells from Fanconi's patients cannot be maintained in culture. Recently, a team from the Reproductive Genetics Institute of Chicago isolated a human embryonic stem cell line that carries a Fanconi's gene mutation. This cell line could enable us to study the uniquely human aspects of Fanconi's anemia.

Read the whole thing - there's a lot more.

Enhancing Aging Muscle Regeneration

Medical News Today delivers the latest on understanding and enhancing muscle regeneration: Plasminogen activator inhibitor-1 (PAI-1) "levels appear to increase with aging, and may explain, in part, the loss of repair capacity as we age. [Scientists] plans to see whether manipulating PAI-1 levels can restore muscle repair in old muscles. ... PAI-1 levels also appear to be higher in muscle diseases [in which] muscle repair processes can't keep up with the degeneration caused by the disease. ... The plasminogen system likely has multiple roles in muscle repair. Understanding how the plasminogen system works in skeletal muscle may give some clues to improving repair of different tissues, especially heart, which is similar in many ways to skeletal muscle."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=27304

What The Politicians Are Up To

(From Wired). The US Senate is debating embryonic stem cell research again. While various politicians are in the limelight, it is well worth remembering that this same group of people are those responsible for restrictive anti-research legislation and scaring away private funding - years of blocking progress towards cures for the millions who continue to suffer and die. "Bald and gravelly-voiced from cancer treatments, Specter said the debate itself makes him angry. 'Yeah, well I am, as a matter of fact,' Specter said. 'Try a few chemotherapy treatments and see how you feel' watching others debate medical research funding. 'The potential for stem cells has been held in abeyance much too long.'"

Link: http://www.wired.com/news/medtech/0,1286,68170,00.html?tw=wn_tophead_2

Awakening The Elder Stem Cells

SAGE Crossroads takes a look at our current understanding of what happens to stem cells with age - and what could be done to rejuvenate their capability to heal. "Stem cells are still there in old age; they just seem to be quiescent ... [this is] the next huge area in stem cell research." Scientists have demonstrated that they "can manipulate the stem cell environment to improve the function of its residents. ... After researchers delineate the orchestra of signals that guide stem cells, perhaps we'll no longer have to cover our gray. We'll be able to use stem cells to put the bounce and shine back into tissues in addition to our hair." The prospect of using biochemical cues to reactivate aging stem cells is intriguing, to say the least.

Link: http://www.sagecrossroads.net/Default.aspx?TabID=28&newsType=ArticleView&articleId=123

Viewing The Future Of Bioengineering

It is interesting to step back and assess just where biotech is taking us, how fast science is moving, and where we may be a decade from now. "The ability to sequence an individual's genome for less than $1,000 is a major goal of genome scientists, and nanopore technology has the potential to make personal genome sequencing available for as little as $100 ... we can discover the genetic basis for variation in health among humans ... advances in regenerative medicine, where manufactured tissues infused with cells, developmental nutrients, and growth stimulants can help regenerate nerves or restore tissues." In summary, "this is the 21st century. We expect that we are going to be able to do something about disease."

Link: http://currents.ucsc.edu/05-06/07-11/symposium.asp

Why Programmed Aging is an Attractive Idea

I noticed a post yesterday discussing a comparatively recent theory of programmed aging (which you may recall was mentioned here last year). The author, I think, hits on one reason why the prospect of aging as a genetic program - rather than a complex, messy process of decay - is attractive to those of us thinking about healthy life extension:

It seems easier to tweak the programming in a computer than to try to replace part after part in an old car that is steadily collapsing.

Sadly for would-be genetic tinkerers, the Reliability Theory of Aging and messy, complex, unprogrammed decay looks to be a much more likely model for degenerative aging in mammals.

Understanding A Tumor Suppression Gene

It should be fairly clear from the past decade of research that understanding the underlying biochemistry of disease leads to targeted, effective therapies. From EurekAlert: "A critical event in the development of melanoma and other human cancers is the inactivation of a gene known as 'p16.' Normally, p16 keeps cells from growing rapidly, a condition that sometimes leads to tumor formation. ... The p16 gene works by producing a protein that attaches to [key growth-promotion enzymes], preventing them from performing their function. When the researchers added the p16 protein to colonies of cancer cells in culture, it diminished the size of many colonies, wiping out some of them. It also decreased the total number of cancer cells."

Link: http://www.eurekalert.org/pub_releases/2005-07/uom-rdh070705.php

Nonsense Spreads, Silver Lining Sought

The less helpful side (i.e. most of) the "anti-aging" marketplace is growing, and growing rapidly. From this study, we see the projection that "America's obsession with youth will continue to drive demand for formulated anti-aging products, which will rise 8.7 percent per year to $30.7 billion in 2009." A world in which marketing of useless cosmetics and uncertain practices so greatly outweigh the scientific search for real anti-aging therapies is a world in which we will all age, suffer and die, having spent our irreplaceable resources and time on things that do not work. What is the silver lining? That the light and noise of the anti-aging marketplace demonstrates real desire for longer, healthier lives - desire that could be redirected to support a better way forward than that provided by the frauds, quacks and opportunists.

Link: http://www.marketwire.com/mw/release_html_b1?release_id=90340

Slightly Insider Info: Mitochondrial Protofection Works

From Rafal Smigrodzki - via the Extropy chat list - excellent news on progress made by the research group he works with:

Today our team confirmed our previous preliminary data showing that we can achieve robust mitochondrial transfection and protein expression in mitochondria of live rats, after an injection of genetically engineered mitochondrial DNA complexed with our protofection transfection agent. A significant fraction of cells in the brain is transfected with this single injection even though we so far did not optimize the dose.

This achievement has important implications for medicine: protofection technology works in vivo, and should be capable of replacing damaged mitochondrial genomes.

For those new to mitochondrial research and its relationship with aging and rejuvenation science, you can find more on Rafal's work here at Fight Aging! and details on the importance of repairing mitochondrial DNA damage at Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS) website. In short, this merits celebration! We're going be hearing much more about the repair of damaged mitochondria in the years ahead, firstly to cure specific age-related disease, and then to tackle general age-related damage to the mitochondrial genome.

"More Great Reasons To Be Dead"

Author Damien Broderick pointed to an almost Kassian article on healthy life extension recently. After some economic commentary and sweeping misjudgements of human nature, we hit the punchline:

It is, I suppose, just conceivable that Broderick may be right about the theoretical possibility of indefinitely prolonged life. However, human nature is less malleable than human physiology and ill-adapted to immortality's challenges. I also have my doubts about whether, if offered the everlasting option, all that many of us would take it.

After all, well-adjusted people tend to develop a serene acceptance of finitude. Then again, the sense of an ending is all that makes some lives, especially very long ones, bearable in the meantime.

One would hope that it goes without saying that this is rank and outright nonsense, just like the screeds put out by the likes of Leon Kass. I have nothing against people who want to age and die - but I suspect that they haven't really thought through or otherwise correctly grasped just how much suffering and pain is involved. We humans aren't really all that good at empathy or looking ahead; if we were, you can be sure that we would be far further ahead in medical research.

People eager to inflict death and suffering on others are a different kettle of fish, however. By the standards of this writer, everyone who seeks to cure disease or relieve suffering in the world is maladjusted. I don't really have any comment to make on that - I think it stands on its own as a shining example of foolishness. I have to say that I am continually surprised by the pro-death-and-suffering contingent. It's human nature, I suppose; any set of terrible ongoing circumstances, no matter how ugly and horrific, will give rise to people who attempt to accept and justify it.

EMBO Reports On Aging Research

The latest issue of EMBO Reports includes a fair number of papers on aging, anti-aging and longevity research - very readable for non-scientists, too. Just click on the "Full Text" link beside each article in the table of contents. Promising science and can-do attitude is on display (alongside a few less exemplary papers - but life is a mixed bag); good reading material for the weekend ahead for those of us who support and advocate efforts to greatly extend the healthy human life span. From Arthur Caplan: "Those who want to make the case against treating ageing as a disease must show why human beings are not capable of solving the challenges that a longer life expectancy would create. There is no intrinsic ethical reason why we should not try to extend our lives."

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

On The Free Radical Theory Of Aging

From ScienCentral, more on recent research into free radicals and aging: "Rabinovitch's group genetically engineered mice to produce a natural antioxidant enzyme called catalase. The mice lived 20 percent longer than normal mice - on average they lived five and a half months longer than the control animals, whose average life span was about two years. ... It means that an individual who lives to age 70, now, with the benefits that we achieved in the mice if these could be carried forth to humans, they might live instead to 84 years old. What we have achieved is the best documentation yet that increasing the level of antioxidants in a general fashion can enhance the health and the lifespan of mice."

Link: http://www.sciencentral.com/articles/view.php3?type=article&article_id=218392588

Considering a Bid For Lunch With Ray Kurzweil

As you may know, the Methuselah Foundation - home of the Mprize for rejuvenation and longevity research - is currently auctioning a celebrity lunch with Ray Kurzweil, to be held at a mutually convenient time and location. The auction has been running for a few days now, with healthy bidding between the Immortality Institute full members group and a number of other folks.

Kurzweil is a fascinating individual - a great example of what you can accomplish if you put your mind to it. He has been doing a fair amount of heavy lifting for the popularization of healthy life extension in the wake of his book Fantastic Voyage, co-written with Terry Grossman. Whatever I may think about supplements boosterism and topics such as the timescale of technology progress, Kurzweil's efforts have benefited the wider community of healthy life extension advocates. A world in which more respected, influential people are talking seriously about greatly extending the healthy human life span is a world in which actually achieving this end becomes easier. I would certainly put in a bid for lunch myself were I not involved in some of the volunteer work related to the auction.

The celebrity lunch auction will run through to the end of the Thursday 14th - if you are considering a bid, you have the weekend to think about it and get together five like-minded friends. Lunch with Ray Kurzweil would certainly be something to talk about for a while, and the proceeds are going to the best of causes.

Carbon Nanotubes For Bone Growth

Carbon nanotubes have a way of showing up in every field of science and engineering - regenerative medicine is no exception, as we learn from this EurekAlert report. "The success of a bone graft depends on the ability of the scaffold to assist the natural healing process. Artificial bone scaffolds have been made from a wide variety of materials, such as polymers or peptide fibers, but they have a number of drawbacks, including low strength and the potential for rejection in the body. ... Bone tissue is a natural composite of collagen fibers and hydroxyapatite crystals. Haddon and his coworkers have demonstrated for the first time that nanotubes can mimic the role of collagen as the scaffold for growth of hydroxyapatite in bone." Any improvement in bone regeneration is likely to prove useful for the millions who suffer from osteoporosis.

Link: http://www.eurekalert.org/pub_releases/2005-07/acs-nin070705.php

From Correlation to Mechanism

People expend a great deal of energy attempting to obtain health benefits based on studies demonstrating correlations between aspects of diet, lifestyle and health. Determining underlying biochemical mechanisms is a step beyond, however - it brings precise therapies and explanations for variations in effectiveness of the old strategies. Here, EurekAlert reports on new understanding of some cancer-protective compounds: "Compounds like sulforaphane in broccoli and resveratrol in wine have been shown to prevent cancer. They do that by signaling our bodies to ramp up the production of proteins capable of preventing damage to our DNA. We now have a good idea how that signal works."

Link: http://www.eurekalert.org/pub_releases/2005-07/uoia-urs070805.php

Taking One For the Team

I'm pleased to note that Jay Fox managed to wrangle his way into an interview on the Daily Show, probably to air sometime in the week beginning July 11th. This brave endeavor was accomplished under the theory that there is no such thing as bad publicity, and a certain loss of pride and posture for Jay is worth the attention it will bring to the Immortality Institute and healthy life extension in general. As he notes:

Even if only 1 out of 100,000 viewers of the show becomes interested enough in what we do to become Full Members at some point in the coming weeks or months, then that could mean dozens of new Full Members of ImmInst, representing $2,500 a year in membership dues to help us do projects like the books or the documentary or the conference. As embarrassed as I am to be made the butt of multiple jokes on national television, I'm very optimistic about how this will benefit ImmInst in the short term, and enough short term successes can lead to long term victory in the scientific conquest of death.

By the sound of things, the interview will be par for the course for the Daily Show, so we shall see how it all turns out - and congratulations to Jay for pulling this off.

Back To Social Changes And Longevity

WorldChanging discusses the social and cultural changes likely to develop from the technologies of healthy life extension. It seems self-evident that things will change as healthy life span increases - and equally self-evident that any such change is for the better ... unless you think death and suffering on a massive scale is a positive thing, as Leon Kass seems to. So it puzzles me to see the degree of hand-wringing over "problems" caused by increasing longevity. These "problems" invariably turn out to be caused by damaging, restrictive and downright repressive laws and government programs - enforced retirement being up there near the top of this list of Bad Ideas.

Link: http://www.worldchanging.com/archives/003058.html

Large Brazilian Stem Cell Trial

Following on from more modest trials of first generation stem cell therapies for heart disease, a 1200-member trial is to begin in Brazil. "As for the patients, they will certainly have better quality of life with less need to use medications and fewer hospital visits. And it is also estimated that the new treatment could save as many as 200,000 lives over a three year period." Accumulated damage to heart tissue kills many, many people - approximately 2000 each and every day in the US alone. The heart is a good place to start on regenerative medicine. It is a comparatively unsophisticated organ, requiring less tailored, complex therapies - and any effective therapy will bring health benefits and additional years of healthy life to large numbers of people.

Link: http://internacional.radiobras.gov.br/ingles/materia_i_2004.php?materia=231503

Looking a Little Further Ahead

Via the Gerontology Research Group mailing list, an early reminder of the Eighth International Symposium on Neurobiology and Neuroendocrinology of Aging in July 2006 - in Austria, so an event for those with a travel budget. The list of confirmed presentations and speakers is interesting even at this early date, including as it does "Genetic control of longevity in C.elegans" and "Mitochondrial DNA and aging."

Investing In Embryonic Stem Cell Research

Wired reports, as have others, that private investment in embryonic stem cell research is picking up. From Robert Lanza of Advanced Cell Technology: "With the passage of Proposition 71 there's been an influx of interest in stem cells. We're in a whole new world. We're flush with cash, and just months ago we were struggling as a private company to even make payroll and to keep the phones on." The article notes that "will soon announce an $8 million investment from private and venture investors, with more on the way" and that "the company has nearly tripled in size." Capital investment is the engine of progress - good to see more of it in a field that will produce cures for age-related disease.

Link: http://www.wired.com/news/print/0,1294,68075,00.html

Aging Is Getting Old

(From Tech Central Station). Glenn Reynolds adds his voice to those discussing Aubrey de Grey's latest paper on the state of biogerontology and a cure for degenerative aging. "[Aging] takes healthy vigorous people who can take care of themselves, and it turns them into frail weaklings who require lots of (expensive) supportive care until they expire from some condition to which it has made them more susceptible. ... I've been spending a lot of time in nursing homes lately, and it's quite obvious that the people there have something wrong with them; to suggest otherwise is, I think, little more than a species of denial. Aging is a disease, a disorder, a killer. We should be doing something about it."

Link: http://techcentralstation.com/070605B.html

Predictions, Predictions

We all have our thoughts on - and hopes for - the timeline for healthy life extension (and radical life extension). Here are some from Stephen Gordon at the Speculist:

Last year I speculated that a simple form of life extension therapy would be available within a decade. With less than nine years left to go, I stand by this prediction.

Aging is a very complicated problem. But age therapy is coming soon because the beginning of the answer to aging will be much simpler than a more complete solution that addresses all seven of Aubrey de Grey's age problems.

As Aubrey de Grey has repeatedly pointed out, we don't have to have a complete solution to benefit. In fact, we might live to see a complete solution to the age problem if we live to see the first true therapy for aging. This "bootstrapping" idea means that the time we gain from the first age therapies might help us live to benefit from second-generation therapies, second-generation therapies bootstrap us to the third generation, etc.

I think this is overly aggressive as a timeline for widespread availability of therapies, given the problems caused by regulation and increasing socialism within medicine. I do expect to see some very impressive lab work taking place in 2014 - especially if we research advocates do our job.

No Shame In Seeking Rejuvenation

Randall Parker comments on Aubrey de Grey's latest paper over at FuturePundit. "Aubrey thinks many biogerontologists entered the field when there was little hope of ever stopping or reversing aging. Therefore most entered to satisfy their curiosity rather than to achieve goals which have practical uses. ... But we no longer live in that era when rejuvenation was absolutely out of the question. ... [new technologies] allow increasingly precise and cheap manipulation of biological systems down at the scale of cells and molecules. Computers allow automation and scaling of processes which required enormous quantities of manual labor in past decades. ... Many scientists are already attempting to develop treatments that effectively reverse some processes of aging."

Link: http://www.futurepundit.com/archives/002874.html

Ray Kurzweil Luncheon Auction Underway

The charity auction of a luncheon engagement with inventor, entrepreneur and healthy life extension advocate Ray Kurzweil - author of Fantastic Voyage: Life Long Enough to Live Forever, amongst other books - is now underway at eBay. The luncheon will be held at a time convenient to the winners and Kurzweil, and all proceeds will go to the Mprize for rejuvenation and longevity research. The Mprize, brainchild of biomedical gerontologist Aubrey de Grey and entrepreneur Dave Gobel, aims to encourage scientists to develop real, working medicine capable of repairing and reversing age-related degeneration. As Aubrey de Grey points out, the scientific community is close enough to this goal that every day counts.

Link: http://cgi.ebay.com/ws/eBayISAPI.dll?ViewItem&item=5592464719

More Good News For Parkinson's Research

From EurekAlert: "Analysis of the brain of a patient suffering from Parkinson's disease has shown for the first time that an experimental treatment can reverse the loss of nerve fibres.
Analysis of the brain of a patient suffering from Parkinson's Disease has shown that the experimental treatment he received caused regrowth of the nerve fibres that are lost in this disease. ... This is the first neuropathological evidence that infusion of GDNF in humans causes sprouting of dopamine fibres, in association with a reduction in the severity of Parkinson's Disease. ... GDNF, which stands for glial cell line-derived neurotrophic factor, is a natural growth agent needed by brain cells to produce dopamine." Any progress towards therapies for neurodegenerative diseases is good news for the future of healthy life extension.

Link: http://www.eurekalert.org/pub_releases/2005-07/uob-rhf063005.php

DNA Damage And The Immune System

Interesting research into the mechanisms by which the immune system responds to DNA damage is reported at EurekAlert. "Our study is the first to show that there are mechanisms in place for the immune system to identify cancer cells. It reveals how natural killer [NK] cells distinguish something they're supposed to get rid of versus something they're supposed to keep. ... What's new about our study is that we found that cells with damaged DNA can also involve other cells in the fight, triggering a mechanism that signals other cells - specifically NK cells - to attack. It could be another ingenious trick that the body uses to ward off cancerous cells." Understanding existing mechanisms for removing cells with damaged DNA is a step on the path towards SENS technologies to repair the causes of aging.

Link: http://www.eurekalert.org/pub_releases/2005-07/uoc--nsf070105.php

From Michael Rae

Michael Rae is Aubrey de Grey's research assistant and a man who writes a mean post (and a great article) once he gets going. Here is a good example on the Mprize, aging research and other related topics, made in response to Matt Piles on the Calorie Restriction Society mailing list. I'll let him take it from here:

Matt Piles wrote:
> Michael wrote:

>> Solution: don't get biologically old ;). Keep your
>> Calories low; speculatively, also keep your long-chain PUFA and
>> dietary cholesterol intakes low; and be a luddite
>> in the engines of aging by giving till it
>> hurts to the MPrize .
>
> Actually in my view this would be a huge waste of
> money. Especially if it hurts...... Aubrey de Grey
> grossly misunderstands what motivates biology
> researchers. The analogy with the Ansari X-Prize for
> example is false. In contrast to aerospace engineers,
> gerontologists can easily get *tons* of money from the
> government.

That depends on which "gerontologists," and what exactly they want to do with the money. The NIA curretnly has a budget of just over US$1 bn. Of this, more than half now goes into Alzheimer's disease (plus the amount invested separately by NIMH, NB); much of the rest of its budget goes into other specific diseases; and a large chunk also goes to geriatric (ultimately, palliative) medicine and to "social gerontology" (ie, how to set up social structures to support the frail elderly).

Richard Miller has pegged the total NIA budget actually allocated to the biology of aging at "somewhere between six and ten million dollars a year" [1] -- a blip that would hardly be missed in the US biomedical research budget.

Even this gives an overoptimistic picture of the funds available for INTERVENTION, because almost all gov't-funded biogerontology expenditure is going into curiosity-driven descriptive studies -- trying to tease out the metabolic origins of aging -- and not into intervention-oriented work. Even most CR work, after the failure of the (relatively) massive Biomarkers of Aging study's flop, is oriented toward its impact on specific diseases, or toward testing theories of aging causes, or trying to figure out its human extrapolability, and not into actually doing something about aging as a disease in need of biomedical solution.

I actually asked Huber Warner, the outgoing director of the NIA, why the NIA wouldn't put more money into intervention-oriented work at the last AGE conference. After first either greatly misunderstanding, or trying to politely duck, this question by talking about the difficulties of so-called "accelerated aging" models, he ultimately gave a response that made Aubrey smile in the way that a police officer who's just extracted a confession of a horrible crime must smile. Because Warner's response appeared to confirm key elements of the nasty "vicious circle" that Aubrey has long held to be holding back serious work on anti-aging biomedicine. He said that they receive very few applications for such work, and that the NIA's internal "peer" review process tends to shoot most such proposals down. As I have written in my previous, major post on the MPrize:

Also, gov't funded researchers are not exactly at liberty to pursue whatever they want. They have to write up proposals to explain exactly what they want to do, and exactly why. And here, a nasty vicious circle gets started. Because the people doing the funding decisioins, while they are scientists, are (in their capacity as funding allocators) first and foremost bureaucrats, with political masters. Crazy-sounding (to politicians, or to their electorate) schemes to "engineer negligible senescence" are deadly to a political or bureaucrataic career. Ironically, because of its less cut-and-dried nature, similar bureaucracies in the arts (eg. the NEA in the 'States) are actually more insulated from their political masters, because they can defend the allocation of funds to (say) an exhibition of crucifixes smeared with an assortment of bodily exudae on freedom of expression grounds, and because art is by its nature in the eye of the beholder; neither defense clearly applies for scientific work.

So scientists continue to pursure relatively modest, uninspiring projects, and to couch their work in modest, uninspiring terms. "We're not looking for a cure for aging. We'd just like to learn how to delay some of the diseases of aging so that Granny can be more comfortable in her old age."

This reinforces the impression, in the mind of the electorate, of a scientific consensus that real intervention in the aging process is impossible at this time. This reinforces the pressure on politicians not to have government funding 'wasted' on such work. Which reinforces scientists playing it safe. And 'round and 'round ...

So how do we break out of these self-perpetuating systems?

In the post in question, I say: the Prize.

Despite his rivalry with de Grey, Richard Miller (unsurprisingly) agreees about the basic structure of the logjam:

"Scientists and their patrons -- even those who have legitimate research interests in interventional gerontology -- do not wish to be seen hanging out with [purveyors of useless nostrums]. Perhaps for these reasons, discussions of research on life span extension are carefully skirted in political discourse at the [NIH] and among similar custodians of public funding. One can sometimes get away with cautious circumlocutions ("we do research on the causes of late-life illnesses"), but to be safe, it is clearly better to focus on how to "add life to years" and how "to learn the secrets contributing to a healthy old age." A president who publicly committed the government's resources to research on extending peoples' life span would be deemed certifiable." (2)

He also lists several less important reasons. Having had a lot more close interaction with the biogerontology establishment in the couple of years since the first SENS conference (reminder: SENS 2 is coming this September -- yeah!!), and especially since early this year when I began formally working as Aubrey's research assistant -- I must now, depressingly, add one more factor: most biogerontologists really aren't actually INHERENTLY interested in their field of study. They are simply intelligent people with enormous curiosity and the skills to do science, who like to exercise their brains and beakers, and who will pursue whatever project that they can get funded that allows them to do so. They got into biogerontology because, as grad students, someone had a grant doing aging-related work, and they just kept pursuing the resulting trajectory -- or, they repackaged their existing work as being in some sense or another "aging research" because the field has recently become somewhat sexier, and perhaps their old niche was not (or was too crowded).

But most biogerontologists would be just as happy to be working in almost any other field of biology: they feel no particular existential urgency about their own aging, nor about the grey holocaust that surrounds them, and would be completely satisfied to simply spend their days teasing apart metabolic pathways and playing with the latest visualization tools for the rest of their careers (which are, of course, doomed to be cut short by the ongoing, progressive, intrinsic degeneration of their bodies and brains -- oops, don't think about that ... focus on your gels ...). They feel no particular urge to damn well DO SOMETHING ABOUT the molecular rot whose progression they so painstakingly document.

This isn't all of them, of course: Richard Miller, Mark Lane, and many of the people who have actually done lifespan calorie restriction (CR) studies (a vanishing breed, alas) are much more conscious of the horrors of biological aging -- and optimistic that something can be done about it -- than their peers. I think, unfortunatley, that the work that most of these folks either are doing, or WOULD be doing if they could somehow beg the farthings, is devoted to a very poor strategy for developing genuine anti-aging biomedicine: the development of CR mimetics and other methods of perturbing the metabolic processes that CAUSE aging damage, instead of work to UNDO the damage itself.

By comparison, the Nationall Cancer Inst gets US$4.7 bn per annum, and almost all of the research dollars (ie, what isn't gobbled up by bureaucracy, outreach, etc) go into work that the researchers have successfully argued will plausibly ultimately result in cures. And it's much more likely that these researchers recognize the seriousness of their work: many of them have watched someone they love suffer and/or die of cancer, and while eveyone has relatives that have suffered and/or died of aging (and everyone has the disease themselves), the nigh-universal state of false consciousness and quietism about the aging plague extends to most biogerontologists as well.

We need to create an independent incentive system, and/or a pump-priming supplement to the existing one, and/or to mobilize the public to demand that the government put money into interventive biogerontology research on a scale proportional to its actual impact on morbidity and mortality -- ie, a scale far exceeding that awarded to the NCI. (As a ballpark: per 1985 figures, the average 50-yr-old woman would gain 2.7 years of life from the utter ERADICATION of cancer from human experience; an effective CR mimetic that could be administered in childhood would gain her over 30 yrs, or more than ELEVEN TIMES as much (2) -- including by greatly reducing the incidence of cancer. Yet it's cancer that gets most of the money: as another ballpark, something like 470 times as much per annum).

The MPrize goes a long way toward addressing all of this.

> And The Methuselah Foundation is viewed
> with suspicion in some circles and even as a bit of a
> joke. Look at Spindler's Web site.
> He doesn't mention that he won one of the Methuselah
> Foundation's prizes.

Well, first, in a real sense he HASN'T won one of the prizes. He was given the inaugural award -- the baseline, against which the first Rejuvenation Prize winners will be judged. This came with no funding at all.

Second, Spindler himself does appear to think that the MMP is a good strategy:

While he concedes that the fruits of his research - in the form of drugs and other biological interventions that could slow aging in the human population - are not likely to appear for several years, Spindler sees tremendous promise in the burgeoning field of anti-aging research. Ventures like the Methuselah Mouse Prize and the research it spurs will help turn skeptics into believers, erasing the public perception that his line of work involves a hopelessly quixotic search for some bogus fountain of youth.

Third, and most important: the impact of the Prize on actual research agendas can't be expected to be much as yet, nor a winner in the near future to trumpet hir results too much, for the simple reason that the Prize is as yet too small. The total pledged pot is now ~US$1.3 million, but most of this is in pledges such as the "300" commitment http://www.mprize.org/index.php?pagename=thethreehundred ; the prize amounts actually available for dispersement are:

Longevity Amount 60,065.84
Rejuvenation Amount 90,329.68

... of which only a percentage will actually accrue on winning, since one only gets a fraction of the prize money available for the Prize in which one is entered, depending on the magnitude by which one exceeds the existing record (see http://www.mprize.org/index.php?pagename=structure ). Even the full $150K would not cover a single mouse lifespan study; a mere slice of said jackpot clearly is not a significant incentive.

To determine if something is a good bet or investment, you take the value of the anticipated reward, subtract the cost of the wager/investment, and multiply by the odds of its occurrence, and compare the result with a similar analysis of all the other things one might do with the wager (including sticking it in one's pocket). The course of action with the greatest result is the rational course of action. If the reward is, as in this case, LESS than the investment risked, and the odds are not overwhelmingly favorable, it's a bad bet.

So as yet, no one is actually gambling. The contestants to date are signed up either for ideological reasons (Bartke) or for publicity (Sinclair) or because Aubrey is just so gosh-darned congenial (Weindruch; probably Leeuwenburgh). When the Prize jumps up by an order of magnitude or two, we can expect a genuine horse race, both because it will actually begin to be a good bet, & becaue the horse race itself will be good enough publicity to make being in the competition valuable to private companies.

> Ergo De Grey's charts about how motivation can be
> altered with the prestige of the prize may be based on
> an utterly false assumption about the prestige of the
> prize.

First, I'm not sure to what chart you refer: the only attempt to estimate the impact of the Prize that I've seen has actual *dollars*, and not prestige, on the X-axis:

http://www.mprize.org/index.php?pagename=lifeline

(Note that I don't take the specific dollar values terribly seriously: it's PAINFULLY back-of-the-envelope. But it does give an accurate impression of HOW it's likely to work based on the history of research prizes).

Prestige as such is not the major reason why the Prize will ultimately succeed. Rather, the Prize will help create radically long-lived mice (and through them, humans) because it will have an award that is actually large enough to (a) keep an academic lab or biotech startup going, and (b) generate excitement and publicity on a scale that (i) is of use to such ventures -- as advertising for private firms (note the enrollment of both Sirtris' Sinclair and Elixir's Guarente), and as a grant magnet for academics -- and that (ii) will rouse the public's anticipation of progress, break their quietism, & spur them to make political and economic demand for a real cure for aging. From a sheer publicity POV, the Prize has been doing very well of late -- but the real effect on the research agenda will come when there really are millions on the table.

And indeed, to the extent that prestige IS a factor, the prestige of a prize is itself in large part a function of its cash value: think about prizes in science or literature, and how much attention tracks dollar value (often explicitly in the media: the XYZ Prize is "the richest prize for Canadian short story writers," "the largest award for an English-language novel," etc. Furthermore, for the political reasons mentioned above, many biogerontologists will shy away from being associated with any efforts to actually intervene -- *now* -- in aging, until the previously-described loggerhead is broken, and the Prize is just too small a juggernaut, as yet, to smash thru'.

To again quote Miller: after listing numerous other political and institutional obstacles to work on genuine anti-aging interventions (the length of time needed to do lifespan studies; the profitability of existing -- yet ineffective and/or unproven -- "anti-aging" "treatments;" active opposition to interventive biogerontology by the Kass gang; etc -- he concludes that "the obstacles blocking the development of the hypothetical discipline of applied gerontology are at this point about 85% political and 15% scientific, and *they will not be overcome by biologists alone*."

I doubt that Miller would publicly endorse the Prize, mostly because of the ongoing feud between him and Aubrey about the proper strategy through which to pursue anti-aging interventions (rather than about the moral imperative to do so -- a subject on which they are in vigorous agreement). However, I suspect that in the secrecy of his own heart he thinks it's a great idea. The MPrize is exactly in a position to deal with this latter side of the equation -- & once it becomes big enough, with the side that is dependent on the scientists and their institutions (academic and capitalist) as well.

> The best thing to do is invest in the right private
> sector research companies,

First, as explained in the previously-linked post and elsewhere, there is a perverse set of anti-incentives keeping VC from seriously pursuing interventive biogerontology. And indeed, thus far, companies originally set up to do so (most prominently, Geron, Elixir, and Sirtris) have all eventually gone into panicked retreat at the behest of impatient financiers, redirecting the intellectual property and reserve of knowledge and skills built up during the initial pursuit of real anti-aging therapies into the development of drugs for specific diseases. Investment in such firms won't work unless $ are specifically tied to doing real anti-aging research. The Prize addresses this because its structure ensures that it only pays for actual life-extending therapies -- and only *successful* therapies, at that.

And second, the problem here is where to put that money even when such companies are available as investment options. Bakcing a losing horse does not help the other horses win a race of this kind. If one is Bill Gates, one can afford to invest in a hell of a lot of horses in hopes of getting just one across the finishing line, but for the rest of us, splitting our investment dollars across several firms with promising-sounding ideas isn't likely to actually push forward the date of their success, even if they actually do turn out to have a viable therapy in the making (tho' if one were right one would at least make oneself a tidy sum). The Prize uses a structure which has historically mobilized private investments in the goal valued at at least ten times the size of the prize itself -- and again, the money only goes out when someone actually pulls off the stunt.

> and to write to the NIA.

Yes, please do! Indeed, there are many ways that one can push forward the day when humans will receive the first radically life-extending biomedical therapies; many of them are here:

http://www.gen.cam.ac.uk/sens/how.htm

... and here:

http://www.longevitymeme.org/projects/

The question is how to get a much wider public doing all of this -- how to extend the political agitation and serious market for genuine, radical anti-aging biomedicine by turning the goldfishbowl of committed life extension fanatics into a big tent of soccer moms who become increasingly unwilling to just go about their (brief) lives watching their parents (and increasingly, their peers and themselves) slowly slide further and further into the yet-implacable maw of biological aging -- physical and mental decay, loss of function, suffering, and ultimately, death -- with every turn of the planet's axis.

Donating to the MPrize is, IMO, the most effective way for any individual who isn't obscenely wealthy to waken the sleeping masses, and to leverage hir very limited dollars directly into the incentive systems governing academics and venture capitalists alike.

REFERENCES

1. http://www.sagecrossroads.org/Default.aspx?tabid=57

2. Miller RA. Extending life: scientific prospects and political obstacles. Milbank Q. 2002;80(1):155-74. PMID: 11933792 [PubMed - indexed for MEDLINE]

Linking Aging, Metabolic Disorders

From EurekAlert, signs that the exploration of the biochemical and genetic mechanisms of metabolism is paying dividends: "During the last decade researchers have made a number of important discoveries about the molecular mechanisms regulating aging. This research has suggested the exciting prospect that the rate of aging can be manipulated and slowed, leading to longer human lifespan. A major peer-reviewed [article] describes the intimate links between these pathways of aging and those of metabolic disease, such as type 2 diabetes and obesity. The authors describe how these insights open the door to novel classes of drugs which can be developed to not only treat diabetes and obesity, but also effectively slow the aging process and extend lifespan." It makes for an interesting read, even while being boosterism for the current crop of for-profit ventures focusing on this area of science.

Link: http://www.eurekalert.org/pub_releases/2005-07/bm-npr062905.php

Exciting Times at the Mprize

As Jay Fox notes, the Mprize for anti-aging medicine is making great progress. The prize exists to promote scientific research in the field of rejuvenation and longevity medicine - scientists are close to being able to make large gains in both mouse and human healthy life span, but this can only happen with much greater levels of funding and public support.

The first item of news, which happened to little fanfare so far, unfortunately, is that the Mprize recently celebrated its 50th member of The Three Hundred. In fact, as of now, there are 52 members of the 300, representing 1.3 million dollars in long-term commitments towards the prize. It doesn't sound like much, but when I first became aware of the Mprize, about 13 months ago, there were only 13 members, one fourth of the number today, representing only $325,000 in long-term commitments. So the prize has grown very rapidly in the last 13 months.

More importantly, 13 months ago the Mprize had only collected about $60,000 in cash so far, give or take. Thanks to a roughly $3,000 donation by a very special person, the Mprize just broke the $150,000 mark in cash collected.

Amongst these donors are famous names and organizations, such as Ray Kurzweil, William Haseltine of Human Genome Sciences, the X Prize Foundation, the Foresight Foundation, and others - but the important contributions come from everyday folks like you and I, demonstrating that there is broad support for progress towards healthy life extension medicine.

As you may know if you've been reading the Longevity Meme daily news, the next Mprize event kicks off this coming Tuesday 5th - an auction for a celebrity lunch with Ray Kurzweil, all the proceeds going to the Mprize fund. Round up six friends, pool your money and make a bid when the auction goes live!

How Much Can Human Life Span Be Extended?

Science Magazine recently put together a list of "125 big questions that face scientific inquiry over the next quarter-century" with an article for each question. Coming in the top 25 is our favorite: "How Much Can Human Life Span Be Extended?" As the article notes, "Just 2 or 3 decades ago, research on aging was a backwater. But when molecular biologists began hunting for ways to prolong life, they found that life span was remarkably pliable. ... Can these strategies help humans live longer? And how do we determine whether they will? Unlike drugs for cancer or heart disease, the benefits of antiaging treatments are fuzzier, making studies difficult to set up and to interpret." The more these concepts are discussed, the more funding we will see for further, better healthy life extension research.

Link: http://www.sciencemag.org/cgi/content/full/309/5731/83

Future Of Korean Stem Cell Research

Medical researchers should be given a great deal more respect and freedom from interference than most get - after all, they are working hard to make our lives longer, healthier and better. In this article, BusinessWeek looks at the work of Hwang Woo Suk and the surrounding government-organized publicity. The planned schedule for future work is on the table: "Hopes of giving new life and joy to those suffering from incurable diseases makes me renew my determination ... Hwang's goal is to use laboratory-engineered stem cells to treat rats, dogs, and possibly monkeys for ailments such as damaged spinal cords. If the animal trials go well, in two to three years he'll apply for permission to conduct human trials in Korea and the U.S."

Link: http://www.businessweek.com/magazine/content/05_28/b3942424.htm

CIRM To Begin Funding?

I wouldn't hold your breath, but it looks like the California Institute of Regenerative Medicine may be starting on the disbursement of research funds. This has been held up as groups opposed to embryonic stem cell research have been filing lawsuits left, right and center - expensive legal battles are one consequence of a public funding mechanism, alongside many other forms of waste and inefficiency. From SFGate: "Officials leading the California Institute for Regenerative Medicine say they have reached 'essential agreement' with legislative foes to settle disputes about conflicts of interest and open meetings. Other contentious issues involving intellectual property and patent rights have yet to be settled. But even some staunch critics of the stem cell institute say the biggest fight seems to be winding down."

Link: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2005/07/02/BAGO4DI5N71.DTL

Aubrey de Grey on Resistance to Debate

In an excellent piece published at EMBO Reports, biomedical gerontologist Aubrey de Grey expands on past comments on the lack of scientific and public debate over a cure for aging.

A perennial complaint in biogerontology, and one whose legitimacy I would be the last to dispute, is that public funding for ageing research is far lower than it should be. Such funding has roughly kept pace with biomedical research spending as a whole, but much more is warranted because postponement of ageing would have a far greater impact on public health and healthcare spending than postponement of any or all of the major age-related diseases. Here, I discuss whether our obstinately modest funding is due, as most of my biogerontologist colleagues evidently feel, to a failure on our part to communicate the scientific and biomedical realities to our political paymasters, and is therefore best rectified by continuing to repeat the arguments we have used for decades until they sink in. I argue that it is instead because those arguments are genuinely weak. I then discuss whether our neglect of more effective justifications for greater investment in biogerontology research is because we overlook key components of the trade-offs that determine funding policy, or whether the problem is the failure of most biogerontologists to maintain an open mind concerning the scientific options. I conclude that it is for both those reasons. Thus, our field is passing up the opportunity to elevate itself to its rightful level of public appreciation and investment, with the result that much longer healthy lives are being denied those who will die before 'real anti-ageing medicine' arrives unless we start working harder towards it now.

As usual, Aubrey de Grey goes on to make detailed points and suggestions - many of which will be familiar to those who have read his past thoughts on the topic. He has made a convincing scientific case that - with adequate funding, public support and directed research programs - the research community knows enough to get started and is within decades of technologies that can greatly extend the healthy human life span. New medicine to address the root causes of degenerative aging would greatly reduce the staggering ongoing toll of suffering, disease and death that claims tens of millions each year.

The scientific path ahead towards healthy life extension technologies is as clear as the future of science ever gets. The problems all lie in matters of funding, scientific and public support and understanding. This is why activism, advocacy and education are vitally important, both within and without the scientific community.

For Auction: Lunch With Ray Kurzweil

Via the GRG mailing list: Ray Kurzweil - scientist, inventor, life-extension visionary - has volunteered to donate his time for a celebrity lunch auction, all of the proceeds to go straight into the Mprize for rejuvenation and longevity research! The auction will open on eBay on Tuesday, July 5. Bidders can join together in groups of up to 6 to win the luncheon with Kurzweil, but groups should select one person to do the actual bidding on eBay on behalf of the group. The auction will be arranged at a time convenient to the winners and Dr. Kurzweil. Lunch will be provided by Mprize volunteers according to the dietary guidelines set forth in Dr. Kurzweil's most recent book, Fantastic Voyage: Live Long Enough to Live Forever.

Link: http://www.mprize.org/auction/

Yet More Thoughts on Weight Loss, Obesity, Life Expectancy

A long post from Randall Parker will no doubt be of interest to those who were following the back and forth over weight and life span not so long ago.

Brace yourselves for a study which produced results which are, to say the least, counterintuitive. A group of Finnish researchers found in an epidemiological study on twins that those overweight people who intended to lose weight who lost weight were most at risk of dying over the study period. (the higher the hazard ratio the greater the risk of dying).

...

But don't rush to conclusions. Epidemiologist Meir Stampfer of the Harvard School for Public Health says epidemiology studies of the effect of weight on mortality need to correct for a number of problems.

I take all of this to indicate that not becoming overweight in the first place is a good thing - but then you knew that already, right?

Gene Therapy To Repair DNA Damage

Repair of damaged DNA is of interest for advocates of healthy life extension; accumulated DNA damage is one root cause of age-related degeneration. It's likely to be a long haul to the introduction of technologies that can patch up varied wear and tear on DNA, but scientists can currently use gene therapies to repair specific classes of damage. As ScienceDaily reports, "Harnessing the strength of a natural process that repairs damage to the human genome, a researcher from UT Southwestern Medical Center has helped establish a method of gene therapy that can accurately and permanently correct mutations in disease-causing genes." This is useful in and of itself - many diseases have a basis in malformed genes - and we should see much more investment in this area in the years ahead.

Link: http://www.sciencedaily.com/releases/2005/06/050630062352.htm