For you serious readers, some say Dr. Leonid Gavrilov’s book, Biology of Life Span: A Quantitative Approach, has the potential to change the future of this country for the better, if its ideas reach members of Congress and other representatives of the U.S. government. Get more information at http://tinyurl.com/5x5ror

Now we’re going to wrap up our previous discussion about how we’re going to fund extreme life extension research.
How about all the private money? Where is it all going? Unfortunately, many popular investments may be ruining your health and shortening your life instead of extending it. And you may be unknowingly contributing to it. If you are invested in mutual funds, retirement funds, hedge funds, the chances are, you are invested in what I sometimes call “pro-death industries”. They include fast foods, processed foods, alcoholic and soft drinks and tobacco.
These industries make money… lots of it. That’s why savvy money managers invest in them. But they kill in two insidious ways. First, the products can shorten your life. Second, they divert sorely needed funds needed to develop life extending products, technologies and services.
Doesn’t it make sense to commit a portion of your wealth to technologies that cure diseases, promote wellness and extend healthy life?
Sure, we can wait until large funding sources finally catch up. Meanwhile though, over 100,000 lives get snuffed out every single day from aging. A five year delay equates to 185 MILLION more lost lives. Scientists tell us they can start making an impact with only a few million more dollars per year, so we simply can’t wait for nature to run its course. A delay could cost you or a loved one your life.
So I urge you to do three things:

Incorporate the 7 simple steps outlined in Life Extension Express into your life and gain 5-20 years... or more from the health steps you practice now. You will create a brighter tomorrow for yourself when you take some simple steps today.
Invest in some of these technologies or donate to Maximum Life Foundation, Methuselah Foundation, InnerSpace Foundation or Immortality Institute to support them.
Keep abreast of advances and breakthroughs that could push you over the longevity finish line.

As I see it, extreme life extension in our lifetimes will ultimately depend on several factors: (a) how much funding we can raise; (b) how soon we can raise the money; (c) how well you take care of yourself in the interim and (d) your ability to dodge accidents, warfare, terrorism, natural disasters or epidemics. Don’t wait until it’s too late – and then wish you would have spent a little time, money and effort for prevention.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

More Compelling Reasons to Exercise (August 22 2008) http://pmid.us/18716044
Here is another study to add to the huge stack of research telling us that exercise is good for healthy longevity: "We determined whether reduced insulin sensitivity, mitochondrial dysfunction and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity. Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older people but no age-effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated in endurance trained individuals. ... The results demonstrate that reduced insulin sensitivity is likely related to changes in [level of body fat] and physical inactivity rather than an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age at the level of mtDNA abundance, nuclear transcription factors, and mitochondrial protein expression. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction."

Ouroboros on Biomarkers and Telomere Length (August 22 2008) http://ouroboros.wordpress.com/2008/08/21/telomere-dysfunction-markers-as-biomarkers-of-aging/
From Ouroboros: "How old are you? At present, the best experimental approach to that question is to inspect your driver's license; we are very good at measuring chronological age, but far worse at measuring physiological age. Until we have such a tool, questions like 'how rapidly is this individual aging?' and 'is this treatment having a positive effect on the rate of aging?' will be meaningless. So, the race is on to find useful biomarkers of aging. Telomere length is a tantalizing biomarker for the aging process: it's positively correlated with life expectancy and negatively correlated with stress and disease. If telomere shortening is a biomarker of aging, then the measurable consequences of telomere shortening should also function as biomarkers, i.e., aging bodies should contain high levels of factors secreted by cells with dysfunctional or critically short telomeres. According to a recent paper by Jiang et al., this is indeed the case. The proteins identified here accumulate with age - [and] they accumulate faster in subjects who are both aged and suffering from age-related disease; in other words, in people whom we might intuitively assign to the 'more rapidly aging' category."

Weight Gain Cast as a Result of Neural Damage (August 21 2008) http://www.eurekalert.org/pub_releases/2008-08/mu-kc082108.php
Hopefully you don't need more reasons to eat a sensible diet by now, but here's another. EurekAlert! passes on a theory to account for what happens to those of us who load up the carbohydrates over the years: "key appetite control cells in the human brain degenerate over time, causing increased hunger and potentially weight-gain as we grow older. Appetite-suppressing cells are attacked by free radicals after eating and [the] degeneration is more significant following meals rich in carbohydrates and sugars. People in the age group of 25 to 50 are most at risk. The neurons that tell people in the crucial age range not to over-eat are being killed-off. When the stomach is empty, it triggers the ghrelin hormone that notifies the brain that we are hungry. When we are full, a set of neurons known as POMCs kick in.. However, free radicals created naturally in the body attack the POMC neurons. This process causes the neurons to degenerate over time, affecting our judgement as to when our hunger is satisfied .The free radicals also try to attack the hunger neurons, but these are protected by the uncoupling protein 2 (UCP2)." So eat more over the years and suffer neural damage that makes it harder not to eat more. We all have free will, but why make it harder for yourself?

Menstrual Blood as Source of Adult Stem Cells (August 20 2008) http://www.sciencedaily.com/releases/2008/08/080818220609.htm
Like heart damage, peripheral artery disease is open to comparatively simple stem cell therapies based on cell transplants. All that is needed is a low-cost source of suitable stem cells. From ScienceDaily: "Cells obtained from menstrual blood, termed 'endometrial regenerative cells' (ERCs) are capable of restoring blood flow in an animal model of advanced peripheral artery disease. A new study demonstrates that when circulation-blocked mice were treated with ERC injections, circulation and functionality were restored. [Researchers have] already performed clinical trials with adult stem cells for patients with peripheral artery disease. The advantage of ERCs is that they can be used in an 'off the shelf' manner, meaning they can be delivered to the point of care, do not require matching, and are easily injectable without the need for complex equipment." The ease with which a therapy can be implemented makes a great deal of difference to the speed with which it moves from laboratory to clinic.

Building Blood from Stem Cells (August 20 2008) http://www.timesonline.co.uk/tol/life_and_style/health/article4567387.ece
The Times has more on growing blood from stem cells: "Vials of human blood have been grown from embryonic stem cells for the first time during research that promises to provide an almost limitless supply suitable for transfusion into any patient. The achievement by scientists in the United States could lead to trials of the blood within two years, and ultimately to an alternative to donations that would transform medicine. If such blood was made from stem cells of the O negative blood type, which is compatible with every blood group but is often in short supply, it could be given safely to anybody who needs a transfusion. One of the biggest safety hurdles that must be cleared before stem-cell therapies enter clinical trials is the risk of uncontrolled cell growth causing cancer. Red blood cells, however, do not have nuclei that carry the genetic material that goes wrong in cancer, and thus should not present this danger. While a few red blood cells have been created from embryonic stem cells before, the ACT team is the first to mass-produce them on the scale required for medical use. They also showed that the red cells were capable of carrying oxygen, and that they responded to biological cues in similar fashion to the real thing."

A Profile of Robert Lanza (August 19 2008) http://discovermagazine.com/2008/sep/19-fighting-for-the-right-to-clone/article_print
Discover Magazine looks at one of the noteworthies of the stem cell research community: "The value of therapeutic cloning has long been clear to Lanza, who did his early work with South African heart transplant pioneer Christiaan Barnard. Starting from those early days, Lanza understood that the barrier to tissue transfer was rejection by the recipient. From an entire organ to a dose of embryonic stem cells, if the tissue's DNA came from anyone else, the transplant would be rejected without the aid of harsh immunosuppressive drugs. 'The treatment could be worse than the problem,' Lanza found. But embryonic clones, the source of an endless supply of stem cells imprinted with one's personal DNA, could alter the equation in favor of the patient and augur a paradigm shift in medicine on par with the changes brought about by antibiotics and vaccines. With the ability to become all of the blood cells - including your immune cells, red blood cells, all of your blood system, as well as vasculature, [hemangioblasts] have been biology's holy grail. What we discovered is that we can create literally millions or billions of these from human embryonic stem cells. We can use transient, intermediate cells like hemangioblasts as a toolbox to fix the adult so you don't have to have limbs amputated, so you may not have to go blind, to prevent heart attacks."

More DNA Damage Research, In Mice This Time (August 18 2008) http://pmid.us/18565572
What does nuclear DNA damage have to do with aging? The correlation is clearly there - older animals have more random nuclear DNA damage - but the mechanism by which increased damage might lead to some portion of degenerative aging is up for debate. A recent paper shows that the correlation extends to calorie restriction and some genetic manipulations that extend life: "Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis significantly increase life span in the mouse and reduce multiple symptoms of aging, including cancer. To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line [to] measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf. Results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR."

Funding Extreme Life Extension Research

posted on August 25, 2008

Incorporate the 7 simple steps outlined in Life Extension Express into your life and gain 5-20 years... or more from the health steps you practice now. You will create a brighter tomorrow for yourself when you take some simple steps today.
Invest in some of these technologies or donate to Maximum Life Foundation, Methuselah Foundation, InnerSpace Foundation or Immortality Institute to support them.
Keep abreast of advances and breakthroughs that could push you over the longevity finish line.

Financial Support for Aging Research

posted on August 18, 2008

Last week, we talked about the potential (optimistic) cost to reverse aging within the next couple of decades.
Historically financial support for aging research and efforts to extend the healthy lifespan has been spotty. Venture capital firms typically aim for profitable exits from their investments within two to four years. The research and product development we support typically takes longer to mature. Governments aren’t providing much funding. Pharmaceutical and biotech companies’ support of basic aging research is hindered due to the fact that there are no generally accepted biomarkers for human aging that would allow the FDA to approve a drug designed to slow the aging process. These companies are forced to develop drugs for specific diseases. And the FDA doesn’t recognize aging as a disease.
For example, The New York Times looks at Sirtris Pharmaceuticals: "The hope is that activating sirtuins in people would, like a calorically restricted diet in mice, avert degenerative diseases of aging like diabetes, heart disease, cancer and Alzheimer's.”

Dr. Christoph Westphal, the chief executive of Sirtris, said of the potential of the resveratrol based drugs they are developing, “I think that if we are right, this could extend life span by 5 or 10 percent.” He added that his goal was to develop drugs against specific diseases, with the extension of life being “almost a side effect of our medicine.”

There is no FDA category for longevity drugs, so if the company is to submit a drug for approval, it needs to be for a specific disease. However, longevity is what has motivated the researchers and what makes the drugs potentially so appealing.

There you have the most serious problem facing longevity science today. The FDA does not allow its direct application. Until this changes, no serious investment will be made in the US to bring longevity science to the clinic. This is a tragedy of astronomical proportions and is beyond belief.
Congress did supplement scarce aging research dollars by establishing the National Institute on Aging in 1974, but that money has primarily gone to disease specific research, such as Alzheimer's disease, or towards the behavioral aspects of aging.
Next week, we’ll look at the possibilities of significant private money finally joining the hunt.
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VOTE FOR "UNDERGRADS AGAINST AGE RELATED DISEASE"

I don't know if you're familiar with the American Express Members Project: It is an open vote to determine how that company will set up a philanthropic program. One of the suggested projects was put forward by a Methuselah Foundation volunteer, and we're looking for enough votes to move it into the next round of consideration:

"You can help by voting: it's free and won't take more than a few minutes. We just need you to go to the Members Projects website and nominate the "Undergrads Against Age Related Disease" project. You don't need to be an Amex card holder, but you do need to be a US resident."

You'll find the project description at the following link:

http://www.membersproject.com/project/view/BVVE2C

"A program that utilizes college undergraduates to perform research in a variety of scientific venues surrounding fighting age related diseases such as Alzheimer's, Parkinson's, Heart Disease, [Cancer, and] overall extension of healthy human life. Hiring researchers is exceedingly expensive. By outsourcing projects to undergraduate students, laboratory use and labor costs are negligible, and the students receive college credit for their work"
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LATEST HEALTHY LIFE EXTENSION HEADLINES

Towards Tissue Engineered Corneas (August 15 2008) http://www.hindustantimes.com/storypage/storypage.aspx?id=34901c8e-1148-44b8-ae83-395922ea0f64
From the Hindustan Times: "Half a dozen eye hospitals in India are collaborating with a research centre in Chennai to create the inner layer of the cornea, the vital window of the human eye. Nichi-In Centre for Regenerative Medicine (NCRM) hopes to make corneal endothelium (inside cell layer) available on a commercial scale. About 100,000 people are in need of eye transplant every year, yet only about 10,000 are able to get donated eyes. The wait for a donor can be endless for the other 90,000. Imagine what a boon it will be if an eye stem cell bank could provide these lab generated endothelial layer of the cornea. The eye has three main parts. The first is the cornea, which is a transparent film like structure that transmits light into the eye. The other two are the lens and retina. During eye transplant, only the cornea is taken from the donor, not the whole eye. Nichi-In is now growing the animal and human corneal inner layer cells on a nano-scaffolding. The research centre is hoping to begin phase I clinical trials on humans in six months."

Ouroboros on Open Science (August 15 2008) http://ouroboros.wordpress.com/2008/08/14/opening-science-how-unconferences-changed-my-life/
Open science, analogous to open source software development, is the way of the future. It greatly increases diversity and speed of work by lowering the cost of information, and thereby allowing many more people to participate in research. In a world in which information transmission is easy, it makes no sense to lock up scientific data. Publish early, publish often should be the mantra. From Ouroboros: "The world implied by these concepts is one of radical sharing, in which credit still goes where credit is due but by dramatically different mechanisms. Open science isn’t so much 'pay it forward' (though there is a bit of that) as an effort to create a (scientific) world in which no one is paying at all, a world in which there's no incentive to withhold or protect ownership of data. The science fiction writer Iain M. Banks once wrote that 'money implies poverty' - indeed, many of the current models of data ownership and publication, and their accompanying 'currencies' of proprietorship, prestige and closed-access publication, imply a world in which data is scarce and must be hoarded. But data is not scarce anymore."

Cryonics Versus Rejuvenation Medicine (August 14 2008) http://www.depressedmetabolism.com/2008/08/13/thomas-donaldson-on-cryonics-and-anti-aging/
Via Depressed Metabolism, arguments for a present focus on the development of cryonics over the development of rejuvenation medicine: "In his article 'Why Cryonics Will Probably Help You More Than Antiaging' (2004), cryonics activist Thomas Donaldson contrasts cryonics with antiaging as a means to life extension and argues that a major advantage of cryonics is that cryobiology research can move at a much faster pace than anti-aging research, especially as it pertains to humans. Not only that, but its progress almost totally lacks the problems of proving that an advance has happened. The state of a brain, or even a section of brain, after vitrification and rewarming to normal temperature, shows directly whether or not the method used improved on previous methods. Cryonic suspension is able at least to preserve our brains in a reversible form, allowing restoration of vital functions and looks likely to come much sooner [than rejuvenation medicine]." Which is all true - but problems left to other people to solve have a way of remaining unsolved. We should work on both cryonics and rejuvenation medicine, not leave the latter for future generations.

Removing the Worst Aspect of Chronic Infection (August 13 2008) http://www.eurekalert.org/pub_releases/2008-08/eu-twb_1080808.php
An important aspect of immune system aging is the lack of naive T cells resulting from long periods of chronic infection by viruses like cytomegalovirus. What if we could reconfigure the immune system to behave more rationally when presented with recurring threats, and thus not exhaust its resources? That might be a possibility: "preventing white blood cells' circulation by trapping them in the lymph nodes can help mice get rid of a chronic viral infection. Laboratory mice can fight off infection by the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), but are vulnerable to chronic infection by a variant called clone 13. Infecting mice with the Armstrong strain sequesters white blood cells in the lymph nodes, while clone 13 does so less stringently. Our hypothesis was that if we could artificially induce conditions like those produced by the Armstrong strain, it would help the immune system clear an infection by clone 13. An experimental drug called FTY720 [prevents] white blood cells from leaving lymph nodes. Even if mice have a stable chronic LCMV clone 13 infection, treatment with FTY720 can still improve their immune response against LCMV enough to have them rid it from their systems. FTY720 appears to prevent 'exhaustion' in the group of white blood cells called CD8+ T cells."

Hourglass II: A Carnival of Biogerontology (August 13 2008) http://ouroboros.wordpress.com/2008/08/12/hourglass-ii-a-carnival-of-biogerontology/
From Ouroboros: "Welcome to the second installation of Hourglass, a blog carnival devoted to the biology of aging. The entries are representatives of the excellent (and growing) community of bloggers who are writing about biogerontology, lifespan extension technologies, and aging in general. Anne C. shares a parable about taking care of her friend Nigel the Fish and what that led her to realize about longevity: specifically, that environment is critical, and that the combination of extrinsic factors that one might collectively term 'nurture' can make all the difference between a short unhappy life and a long fulfilled one. Old and damaged cells enter a permanent growth arrest known as senescence, which is both good (because they can’t initiate tumors) and bad (because persistent senescent cells behave in a ridiculously antisocial manner, secreting growth factors and proteases that both encourage nearby tumors to metastasize and degrade tissue function). At his new site Anti-Ageing Research, Dominick Burton discusses ways in which specifically targeted cancer therapies might be adapted to attack senescent cells instead."

Building Better Tendons (August 12 2008) http://technology.newscientist.com/article/dn14512-labgrown-tendons-gradually-fade-to-bone.html
Laboratory tissue engineering continues to improve in sophistication, as noted by the New Scientist: "only now have researchers managed to make different tissues blend into one another, as they do naturally in the body. Such gradients are necessary for some structures and organs to function properly. In the body, gradients like this strengthen the ends of tendons that attach to bones. Currently, lab-grown tendons put into the body often fail at the attachment end because they lack this property. The new technique should lead to more lifelike artificially-grown tendons, and better treatments for injuries like ruptured Achilles tendons.
The technique could also be applicable to other tissues, such as blood vessels. At the heart of the new technique is a gene that triggers the fibroblast cells that make up tendons to start forming bone. The team used viruses carrying that gene to transform a tendon made from normal fibroblasts into one with a gradient of bony properties. So far, the researchers have shown that tendons made this way are stable when implanted under the skin of rats. The next step is to graft a tendon to connect bone and muscle in a rat and see if it really does perform better."

Demonstrating the Value of Exercise (August 12 2008) http://www.medicalnewstoday.com/articles/117929.php
Via Medical News Today, another reminder of the value of exercise: "US scientists comparing middle aged and older regular runners with healthy equivalents for more than 20 years found that vigorous regular exercise was linked to longer life and less disability in old age. Fries and his team had 538 members of a nationwide running club and 423 healthy controls from northern California fill in questionnaires every year for as long as they could, from 1984 to 2005. The mean disability score was higher for the controls than the runners at all stages of the study and went up with age in both groups, but on average, for runners the onset of disability started later. Runners' initial disability was 16 years later than nonrunners. Runners had a significantly lower risk of having a disability score of 0.5. 19 years into the study, 15 per cent of the runners and 34 per cent of the controls had died, and after adjusting for possible confounders, runners showed a greater chance of living longer. The differences in disability and longevity between the runner group and the control group continued to diverge at the end of the study, as the participants approached their 80th birthday."

Full Paper on Visceral Fat and Longevity (August 11 2008) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2504027
You may recall a solid demonstration that visceral fat tissue negatively affects longevity from earlier this year. The full paper is now open access and available at PubMed Central: "Visceral fat (VF) accretion occurs in obesity and with aging, and a reduction in VF is a common phenotypic change in calorie-restricted [CR] mammals. VF has been shown to be the single most important determinant of metabolic syndrome, and its removal in rats results in improved insulin action and delays the onset of diabetes. Given the hazards associated with abdominal obesity, it seems plausible that the beneficial effects of CR on longevity may be due at least in part to an attenuation of VF. Our data clearly demonstrate that in mammals, VF removal and CR are associated with an increase in mean and maximum lifespan. The mean and maximum lifespan of CR rats was greater than that seen in VF-removed animals, suggesting that the life-prolonging benefit of CR is mediated in part by pathways other than those modulated by an attenuation of VF. By comparing median lifespans, we estimate that the contribution of CR to longevity in this model was 47 weeks, whereas VF removal was 9.5 weeks, as compared to [ad libitum]-fed rats, suggesting that VF reduction offered approximately 20% of the effect of CR on longevity."

The Cost of Immortality

posted on August 11, 2008

We talked a lot about how and why aging can be reversed in our lifetimes, and what you can do to boost your odds to benefit. Let’s now talk a little about how much a project like this might cost.
First, some knowledgeable people think it will never be done in our lifetimes. Nearly every great advance was met with skepticism and derision. But science continues to prevail. It will be the same with aging research.
For those who do believe it is possible, projected timelines extend from something less than MaxLife’s 21 year plan to as much as a hundred years. And some project that the cost will be well over $1 trillion. How about you? What are your opinions? Can it be done? How long will it take? How much will it cost?
We have spent years pondering those questions and running calculation after calculation. After consulting with scientists from all the disciplines we explored, after reviewing business plans and budgets and research plans and budgets, after factoring in the Law of Accelerating Returns and its Deflationary Factor, and after a bunch of educated guesswork boosted by optimism and tempered by the harsh reality of knowing projects usually cost more and take longer than we anticipate, here are our conclusions:

This is not a trillion dollar plus project. In fact, it’s not even a $100 billion project, even though that would be one of the most incredible bargains of all time. We spend that much on health care in this country EVERY 16 DAYS! We came to the astonishing conclusion that we could accomplish enough to reverse aging in humans for the ridiculously low sum of $1.7 billion plus $900 million more for SENS. Total $2.6 billion.
We can do this over a 21 year span, starting from the time the first part of the funding is in place.
This assumes no reinvested profits will be generated from any of the companies and technologies which would receive funding. If some of these were moderately successful, profits could be reinvested, which would reduce the overall cash outlay.

If we’re right, 10,000 health conscious individuals, just like you, could fund MaxLife’s project for $900/month each.
If it costs so little, and even if it does cost over a trillion dollars, wouldn’t this be something governments or big business would fund?
Unfortunately, no!
I’ll continue this topic next week.
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LATEST HEALTHY LIFE EXTENSION HEADLINES FROM REASON

Aging, Inflammation, and Cancer (August 08 2008) http://pmid.us/18671998
Less chronic inflammation, less cancer: "Cancer is generally recognized as an age-related disease. In fact, incidence and mortality rates of most human cancers increase consistently with age up to 90 years, but they plateau and decline thereafter. A low-grade systemic inflammation characterizes aging, and this pro-inflammatory status underlies biological mechanisms responsible for age-related inflammatory diseases. On the other hand, clinical and epidemiological studies show a strong association between chronic infection, inflammation and cancer and indicate that even in tumors not directly linked to pathogens, the microenvironment is characterized by the presence of a smouldering inflammation, fuelled primarily by stromal leukocytes. Centenarians are characterized by a higher frequency of genetic markers associated with better control of inflammation. The reduced capacity of centenarians to mount inflammatory responses appears to exert a protective effect towards the development of those age-related pathologies having a strong inflammatory pathogenetic component, including cancer. All in all, centenarians seem to carry a genetic background with a peculiar resistance to cancer which is also an anti-inflammatory profile."

The Other Application of Stem Cell Science (August 07 2008) http://www.eurekalert.org/pub_releases/2008-08/chb-dac080508.php
EurekAlert! reminds us of the second main application for stem cell science: researchers "have produced a robust new collection of disease-specific stem cell lines, all of which were developed using the new induced pluripotent stem cell (iPS) technique. The cell lines the researchers produced carry the genes or genetic components for 10 different diseases, including Parkinson's Disease, Type I diabetes, Huntington's Disease, Down Syndrome, a form of combined immunodeficiency ('Bubble Boy's Disease'), Lesch-Nyhan syndrome, Gaucher's Disease, and two forms of Muscular Dystrophy, among others. the suite of iPS cell lines [marks] an important achievement and a very significant advance for patients suffering from degenerative diseases. These disease-specific iPS cells are invaluable tools that will allow researchers to watch the development diseases in petri dishes, outside of the patients. And we have good reason to believe that this will make it possible to find new treatments, and eventually drugs, to slow or even stop the course of a number of diseases." Advances that reduce the cost of research and increase efficiency will speed further progress. This is an excellent example of the type.

Another View of Gender Differences in Longevity (August 06 2008) http://www.time.com/time/health/article/0,8599,1827162,00.html
Via Time: "Another more complicated possibility [for women's longevity] is that women have two X chromosomes, while men have one. (Men have an X and a Y.) When cells go through aging and damage, they have a choice in terms of genes - either on one X chromosome or the other. Consider it this way: you have a population of cells, all aging together. In some cells, the genes on one X chromosome are active; in other cells, by chance, the same set of genes, with different variations, are active on the other X chromosome. Don't forget, we all have the same genes - the reason we differ is because we express different variations of those genes, like different colors of a car. Now, if one set of variations provides a survival advantage for the cells versus another, then the cells with the advantage will persist while the other ones will die off, leaving behind more cells with the genes on the more advantageous X chromosome. So, in women, cells can perhaps be protected by a slightly better variation of a gene on the second X chromosome. Men don't have this luxury and don't get this choice."

NOTE: And all this time I thought it was because of the stress women heap on us.

Transhumanism and Engineering Longevity (August 06 2008) http://www.hartfordadvocate.com/article.cfm?aid=9076
From the Hartford Advocate: "Transhumanism is the idea that it's OK to transcend the limitations of the body and brain. Technologies, both large and small, could radically change the human experience. The mind reels with possibilities. Could we become cyborgs, with circuitry and metallic components seamlessly integrated into our bodies? Will there be nano-machines with artificial intelligence coursing through our bodies, fixing medical problems? Will we be able to dump our consciousness into computers or other machines? The possibilities are endless but, at least for now, human lives are not. Slowing body degeneration is a modest goal, and doesn't go far enough for some national anti-aging researchers. Aubrey de Grey, an energetic Englishman with a ZZ Top-length beard, is the chief researcher and evangelist for an anti-aging movement that views aging as a disease that can be cured, and cured soon. I think we have a 50 percent chance of getting there in around 25 years, so long as the early proof-of-concept work in mice is well-enough funded for the next 10 years or so."

Stem Cell Treatments in China (August 05 2008) http://www.informationweek.com/news/management/compliance/showArticle.jhtml?articleID=209902855
InformationWeek looks at one of the organizations that's putting stem cell research into clinical practice in China. The absence of stifling regulation means that this work proceeds much more rapidly, but rigorous data tends to come later in the process. The benefits of patient choice and researcher freedom should be obvious, however. "The company, Beike Biotechnology, uses nonembryonic stem cells to treat a variety of ailments including heart disease and neurological disorders such as cerebral palsy, spinal cord injury, muscular dystrophy, and optic nerve hypoplasia, a primary cause of blindness in children. Beike's technology, which hasn't been subjected to double-blind clinical trials of the sort required by the U.S. Food and Drug Administration, uses a combination of umbilical cord cells and stem cells derived from the patient being treated." The article notes that the company is working towards the near future use of induced pluripotent stem cells in therapy - a pace of development that is impossible in the present US regulatory system.

More Fuel for the DNA Damage Debate (August 04 2008) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2441830
Does the level of random damage to your nuclear DNA - genomic instability - have anything to do with general manifestations of aging? We know the correlation with cancer, but beyond that it's up for debate. This open access paper provides a new line of evidence: "Increasing genomic instability is associated with aging in eukaryotes, but the connection between genomic instability and natural variation in life span is unknown.
We have quantified chronological life span and [genomic instability] in [yeast]. We show that genomic instability increases [during] chronological aging. The age-dependent increase of genomic instability generally lags behind the drop of viability and this delay accounts for ~50% of the observed natural variation of replicative life span in these yeast isolates. We conclude that the abilities of yeast strains to tolerate genomic instability co-vary with their replicative life spans. To the best of our knowledge, this is the first quantitative evidence that demonstrates a link between genomic instability and natural variation in life span."

Epigenetics in Aging (August 04 2008) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2464300
An interesting open access paper via PubMed Central: "Strictly speaking, 'epigenetics' refers to chromatin and DNA modifications that are heritable through cell division, but do not involve changes in the underlying DNA sequence. Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases. It is apparent that chromatin structure does change with aging, in organisms as diverse as yeast and mammals. However, with the exception of Sir2 in yeast, the extent to which this impacts the aging process has not yet been defined. The effects of chromatin on aging are likely to be complex and bidirectional. To test and define the impact of specific epigenetic determinants on aging will be a challenging task."

Your Perfect Cure is Prevention

posted on August 4, 2008

A very close friend of mine’s father seems to have lost his will to live. Here is an aging former soldier of fortune who once had a zest for life experienced by few. Now, he lost interest in eating, in seeing a doctor and seemingly everything else, including his will to live.

This bothers me for a couple of reasons. First, someone close to me may lose her dad. And on a larger scale, didn’t I say most people go to the ends of the earth to hang on to life towards the end? Well, apparently not all. Why is this?

Several months ago, I had a relevant conversation with another close friend about how some people cling to life at the end no matter how much suffering and pain they endure, while others simply throw in the towel. We concluded it may have something to do with declining hormone levels. So I gave my anti-aging physician a call a few days ago to discuss this possibility. His response was that yes, declining hormone levels lead to depression, which usually translates to loss of appetite, and of course, a diminished will to live. He routinely reverses this phenomena with closely monitored hormone replacement therapy (HRT).

Could declining hormone levels be evolution’s way to nudge us into going quietly into the night? Could savvy docs reverse deteriorating attitudes and improve and extend millions of lives with simple HRT?

I think the answer is a resounding YES!

Saturday, I enjoyed a wonderful lunch get together with one of the most esteemed psychologists and authors in history. In fact, he has been one of my personal heroes for about 40 years. He’s now experiencing moments of forgetfulness which he calls his “senior moments”. The difference between him and my friend’s father is he is attacking his challenge head on, while maintaining his witty sense of humor. He’s getting sophisticated diagnostics, will undergo cutting edge treatment and is determined to reverse it.

And reverse it he will, according to a medical consultant who specializes in neurodegenerative conditions.

The moral to this story is, don’t wait until you see serious decline to see an anti-aging specialist. In fact, see one before you experience any decline – period. After all, once you see signs of a condition or disease, it may be too late. Heart disease and cancer are two good examples. They eat away at you for years before you show symptoms. And one symptom from heart disease is often sudden death.

Your perfect cure is prevention.
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THREE DECADES FROM NOW

Under the present weight of regulation, it looks to take about 30 years for a new medical technology to progress from first proof of concept through to widespread and cost-effective availability - for those that aren't buried young by the cost of red tape, that is. Compare that with something more like 20 years in less regulated industries. That difference adds up. But what can we expect to see in the 2030s, based on what has taken place in laboratories and trials in the past few years?

http://www.fightaging.org/archives/001537.php

"Replacement organs will be grown to order from your own cells.
Stem cells will be created, manipulated, and transplanted to direct extraordinary regeneration.
Age-damaged immune systems will be wiped clean and replaced afresh.
Gene therapy will be a mature technology, and genetic disorders curable.
Everyone will know their DNA sequence, and have access to a vast database of knowledge that describes risks, therapies, and best practices.
Cancer will be detected early, and even late-stage metastasis cured with few side-effects by nanoparticle-based, viral, or other therapies.
The important mitochondrial DNA will be replaced when damaged by disease or age.
Many of the biochemical processes underlying the benefits of exercise, calorie restriction, and known human longevity-associated genes will be reproduced by cheap drugs.”

ON STEM CELLS AND AGING

While perusing PubMed Central, Reason discovered a good overview of present thinking on stem cells, stem cell niches, and their role in aging:

http://www.fightaging.org/archives/001536.php

"If many adult tissues and organs are continuously replenished by cells derived from stem cells, then why do they show signs of aging? One possibility is that stem cells themselves age and senesce, resulting in a decreased ability to replace worn-out progeny and/or the fact that they pass on aged phenotypes to their progeny.

NOTE: Pending modest funding, a stem cell company will soon be launched that could solve this problem within a couple of years.

Somewhere at the end of this road of investigation lies the means to keep stem cell populations vital while not exaggerating the risk of cancer due to runaway failure in a stem cell - the most likely reason we have evolved mechanisms that diminish stem cell activity in response to age-related biochemical damage. At some point, the large and well-funded field of regenerative medicine is going to turn its attention to repairing the damage of aging. Many major lines of research presently address age-related disease, and it is becoming clear that the effectiveness of therapies is hindered by age-related damage in stem cells and their niches. We should encourage research in this direction.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

Towards Long Life and Happiness (August 01 2008) http://www.canada.com/components/print.aspx?id=924ef76b-5103-4aad-a596-13278777f8eb
From Canada.com: "Aging - and more specifically, the aspiration to slow human aging - is the most important neglected issue of our time. There are many things that could kill the world's current 6.5 billion plus people, but the vast majority of those currently alive today, especially in the developed world, will die from age-related causes. The diseases of aging could be the real scourge of the 21st century. That is, unless we do something to remedy the biological vulnerabilities we have inherited from our evolutionary history. The current approach to medical research is to tackle individual diseases, one at a time. So we spend large amounts of public funding on basic research into cancer, heart disease, diabetes, Alzheimer's, etc. But we invest very little in understanding the biology of aging and how it impacts our health prospects. Supplementing the current medical approach with one that also tackles aging would help us take a more inclusive approach to health extension. Even if we find a cure for one of the diseases of aging - like cancer - it would only extend life by a few years, as most people will likely be afflicted by one of the other diseases of aging. But if we could modify the biological mechanisms underlying aging, we may be able to significantly increase the number of disease-free years humans can expect to live. This would reap enormous individual and societal benefits."

Exercise in a Pill? (July 31 2008)
http://www.eurekalert.org/pub_releases/2008-07/si-eia072808.php
If researchers could reproduce the biochemical basis for the health and longevity-enhancing results of exercise, the resulting drug would no doubt be as popular as calorie restriction mimetics. Exercise and calorie restriction are the two gold-standard items for health: little else even comes close yet. From EurekAlert!, news of small steps on this path: Researchers "identified two signaling pathways that are activated in response to exercise and converge to dramatically increase endurance. Previous work with genetically engineered mice [had] revealed that permanently activating a genetic switch known as PPAR delta turned mice into indefatigable marathon runners. In addition to their super-endurance, the altered mice were resistant to weight gain, even when fed a high-fat diet that caused obesity in ordinary mice. On top of their lean and mean physique, their response to insulin improved, lowering levels of circulating glucose. We wanted to know whether a drug specific for PPAR delta would have the same beneficial effects."

Short Telomeres and Accelerated Aging (July 31 2008) http://newswire.rockefeller.edu/?page=engine&id=791
All of the rare accelerated aging conditions appear to be caused by one aspect of "normal" aging exaggerated and run wild to cause great biochemical damage. Researchers now think they understand what underlies another of these conditions: "Sufferers of the disease, called dyskeratosis congentia, tend to have problems in tissues in which cells multiply rapidly - skin, hair, nails, tongue, gut and bone marrow - and usually die between the ages of 16 and 50 from bone marrow failure, or the inability to replenish their blood cells. Each time a cell divides, the protective caps at the ends of chromosomes shorten - and when these caps are gone, so are we. Now, by using an unconventional strategy to shorten telomeres in mice, [researchers] have not only created the first faithful mouse model for studying [dyskeratosis congentia], but they have revealed the molecular defect behind the disease. These results suggest that in patients suffering from dyskeratosis congenita, the enzyme telomerase can't elongate telomeres as fast as the nucleases chew them away. Clearly, the next step is to understand how telomeres are degraded in human cells. We need to identify the nucleases at work and find out how they are regulated."

Reduced Protein Intake and Immune Response (July 30 2008) http://pmid.us/18656703
Scientists here demonstrate the connection between reduced dietary protein and a better immune response, already known from the practice of calorie
restriction: "Manipulation of dietary variables is one the most described events to retard the aging process and maintain immune function. The present study deals with the effect of variable dietary protein-carbohydrate ratios (without caloric restriction) on the alteration of immune response of male albino rats. These results thus suggest that diets with variable dietary protein-carbohydrate ratios act as an exogenous modulator of immune response with age and [a low protein] diet may be beneficial to slow down/reduce the impairment of immune response in aged individuals." For comparison, you might also look at studies of methionine restriction without overall calorie restriction. Greater control of diet over the years adds up, and every extra year of health gained can make a big difference when the pace of medical development is rapid.

The Tithonus Error (July 29 2008)
http://www.dailymail.co.uk/news/article-1038717/MAX-HASTINGS-Growing-old-Britain-happy-experience-The-longer-live-worse-quality-life-becomes.html
So many, many people still believe that the result of longevity science will be that you are older and ever more frail for more years, with no hope of death. This is absolutely false: the goals are in fact rejuvenation of the old, repair of the biochemical damage of aging, and the extension of healthy, youthful life. But still people have the fate of Tithonus in mind, sunk into the collective consciousness through a hundred similar cautionary tales. So you'll see this sort of doleful op-ed from the Daily Mail: "To some of us, [longevity] seems a ghastly prospect. I am 62, and find life terrific. I get more work done than ever before, because my children have long ago left home and I remain fit. I take pills to keep my blood pressure down and waterworks functioning. It seems to some of us terrifying to imagine that we might survive to 100. Surely, the drear misery and loneliness that accompanies such age is not worth it for a birthday party, telegram from the Queen and maybe a paragraph in the local newspaper. Once mobility is gone, once the simplest actions of daily life become dependent upon others, it is hard to sustain self-respect. If science indeed continues to lengthen our lives, I believe that we shall have to be given a choice about opting out." The work of advocacy and education must continue - this is a sign that much remains to be done.

Futurist Musings on the Leap Ahead (July 29 2008) http://www.canada.com/topics/bodyandhealth/story.html?id=fa35f402-d10e-4c1e-a8c9-cc3f1cc12f92
From Canada.com: "Genetic science, stem-cell research and extreme caloric restriction are all part of a burgeoning 'immortality industry' that could soon point the way to a fountain of youth with the potential to stretch the human life span to 125 or 150 years, says a sociologist and consultant on future studies. Advances such as nanotechnology - the emerging ability to manipulate extremely small structures - could ultimately make it possible to regenerate every cell in the body. At that point, we can throw out every idea we have about longevity and even mortality itself. The effects of human life-extension will be far-reaching, [potentially] spawning second or third careers in people's extra decades and a society of lifelong students using the gift of more time to continually reinvent themselves with new education. The extension of human life will also depend on people's lifestyle [and] the current obesity epidemic, smoking habits and other unhealthy behaviors indicate they don't always make beneficial choices. People can be 'seduced' by breakthroughs they believe will save them from themselves. I think there is going to be a tremendous chasm between average life expectancy and life potential."

Michael West at Aging 2008 (July 28 2008)
http://www.acceleratingfuture.com/people-blog/?p=2338
Another Aging 2008 transcript from Future Current: "I have been entranced by the immortality of the species and how it's accomplished. A simple way of putting it: we are made of cells, trillions of them, that have been proliferating backward in time all the way through hundreds of millions of years to the beginning of life on the planet, leaving no dead ancestors in their wake ever - or we would not be here. It is our somatic cells that are destined to die. All the cells in our body have this immortal legacy going backward in time millions of years and will face death for the first time ever in our lifetime. What can we learn about the immortality of the species to transport those observations and discoveries of modern technologies into something that will really do something about human aging? How could these cells be used in the next ten years? There are numerous examples I could give you, but one hopeful one - macular degeneration. This is the leading cause of blindness, due to the aging of our retina. These cells have now been made in a form that is appropriate to begin human clinical trials. When they become lost or dysfunctional in the back of the retina, they cause this cascade of pathology that is a leading cause of blindness in the elderly. It is at least one of the top targets for how we hope these cells will eventually be used in medicine."

Cryonics as an Elective Medical Procedure (July 28 2008) http://www.depressedmetabolism.com/2008/07/24/cryonics-as-an-elective-medical-procedure/
From Depressed Metabolism: "The limitation that cryonics procedures can only be started after pronouncement of legal death reflects the unfortunate fact that the current medical establishment does not recognize cryonics as a credible form of advanced critical care. As a result, cryonics is currently practiced as a form of emergency medicine in which conventional resuscitation technologies such as chest compressions and ventilations are used to avoid the kinds of injury that follow after cardiac arrest. Although there will always be a place for cryonics as a form of emergency medicine to treat cases of trauma and sudden circulatory arrest, most patients who currently present for human cryopreservation would benefit from more hospital cooperation in choosing cryonics as an elective medical procedure. Although current cryonics organizations such as Alcor try to make the best of a bad situation by employing standby teams that allow rapid intervention after cardiac arrest to reduce brain injury, much improved quality of care of cryonics patients would be possible if cryonics procedures would start at a point where medical professionals (with informed consent of the patient and/or family) would determine that further treatment of the patient with contemporary technologies would be futile, or even counter-productive.".

Aging, the New Frontier

posted on July 28, 2008

We are finally moving from an era where nothing could be done to defeat aging into an era where advancing technology will give us the tools to overcome it. All the old attitudes are no longer relevant.
We’re so used to people dying from age related causes that we accept it as a normal part of life. And we become desensitized to this death. But let’s look at it from a different angle and see if you think about it differently.
Robert Freitas, a brilliant scientist and perhaps the world’s utmost authority on Nanomedicine, offers some interesting ways to view aging. He points out the following:

100,000 lives are lost every single day from aging related causes. They’re scattered all over the world, so we hardly notice. But what if 400 jetliners fell out of the sky in a single day? We would be astonished, outraged and sickened. Yet effectively, that’s equivalent to 400 jetliner crashes.
If 400 planes crashed every day, wouldn’t the world marshal all its powers to insure aircraft safety, especially if we had no choice but to fly?
What if we could avoid… or at least postpone most aging related deaths?
Then why isn’t treating aging a #1 priority?

After all, if you or a loved one had a major medical condition such as cancer, heart disease or suffered a stroke, wouldn’t you ask for the very best medical care?
If we had a treatment that could reverse Alzheimer’s, Parkinson’s, osteoporosis, arteriosclerosis or diabetes… who in their right mind would turn it down?
Now it is aging, the new frontier. Since it kills everyone who survives or dodges diseases, might not aging be considered a disease as well? MaxLife looks at it as a curable disease, in fact the mother of most diseases. And we’re determined to do something about it.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

The Dreaded Reactive Oxygen Species (July 25 2008) http://www.eurekalert.org/pub_releases/2008-07/uorm-ruk072108.php
It's good to see more research groups looking into targeting antioxidants to the mitochondria. From EurekAlert!: "Researchers have taken a first snapshot of how a class of highly reactive molecules inflicts cellular damage as part of aging, heart disease, stroke, cancer, diabetes, kidney disease and Alzheimer's disease to name a few. Researchers have discovered a tool that can monitor related damage and determine the degree to which antioxidant drugs effectively combat disease. Our study provides a better glimpse of why a cell under assault by disease makes 10 times as many reactive oxygen species [ROS] as the same cell when healthy. We have discovered a chemical tool for investigating how diseases cause damage, mitochondrion by mitochondrion. Efforts to develop antioxidant drugs (e.g. vitamin E) to treat diseases of increased oxidative stress have met with limited success to date because they tried to eliminate ROS, rather than maintain the right amount, Sheu said. He established the Mitochondrial Research & Innovation Group (MRIG) [in] 2002 with the goal of designing therapies to deliver precise amounts of antioxidants to the mitochondria of diseased cells only. MRIG teams are, for example, screening through compounds to confirm that oxidative stress can be reversed by mitochondria-specific drugs."

On Hormesis and Longevity (July 24 2008) http://pmid.us/18648625
A nice overview of hormesis: "Aging is characterized by a stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. In a series of experimental studies we have shown that repetitive mild heat stress has anti-aging hormetic effects on growth and various other cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. These effects include the maintenance of stress protein profiles, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to ethanol, hydrogenperoxide and ultraviolet-B rays, and enhanced levels of various antioxidant enzymes. Anti-aging hormetic effects of mild heat shock appear to be facilitated by reducing protein damage and protein aggregation by activating internal antioxidant, repair and degradation processes."

Yeast and Aging Research (July 22 2008) http://ouroboros.wordpress.com/2008/07/21/biogerontology-rising-recent-progress-in-yeast-aging-research/
Ouroboros looks at the humble yeast in context: "Our understanding of aging in animals owes a great debt to a large body of careful work in a single-celled organism, the brewer's yeast Saccharomyces cerevisiae. Indeed, as I've argued before, yeast is one of the two organisms with the strongest credible claim to have started modern biogerontology. An unusually large crop of yeast aging papers have appeared over the last few months, and I thought it would be appropriate to spend a few paragraphs describing them - in honor of this humble organism that rises our bread, ferments our beer, and has done so much to open our eyes to the fundamental mechanisms of aging. Yeast mutants in worm longevity genes are significantly more likely to be long-lived than randomly chosen mutants - suggesting [that] genes that modulate aging have been conserved not only in sequence, but also in function, over a billion years of evolution. Given this functional conservation, it is reasonable to use yeast to help answer questions about aging in general, so long as these questions as cell-biological in scope."

New York Times on Sirtris (July 22 2008) http://www.nytimes.com/2008/07/22/health/research/22long.html?pagewanted=all
The New York Times looks at Sirtris Pharmaceuticals: "The hope is that activating sirtuins in people would, like a calorically restricted diet in mice, avert degenerative diseases of aging like diabetes, heart disease, cancer and Alzheimer's. There is no Food and Drug Administration category for longevity drugs, so if the company is to submit a drug for approval, it needs to be for a specific disease. Nonetheless, longevity is what has motivated the researchers and what makes the drugs potentially so appealing. Dr. Christoph Westphal, the chief executive of Sirtris, said of the potential of the drugs, 'I think that if we are right, this could extend life span by 5 or 10 percent.' He added that his goal was to develop drugs against specific diseases, with the extension of life being 'almost a side effect of our medicine.'" There you have the most serious problem facing longevity science today: that its direct application is not permitted by the FDA. Until this changes no serious investment will be made in the US to bring longevity science to the clinic. This is a tragedy of so great a scale as to beggar belief.

Thoughts on Mortality and Its Evasion (July 21 2008) http://tacit.livejournal.com/250032.html
An interesting LiveJournal post: "A person immune to the ravages of old age would still not be immune to death; accident, violence, and other misadventure is perfectly capable of ending even a 25-year-old's life. It simply means that person no longer has a cap on the maximum time he can live, if he so chooses. And that's really what it's all about. Choice. If you go into the doctor's office, and he tells you that you have a bacterial infection, which will slowly grow progressively worse until it kills you painfully, then offers you an antibiotic pill that will completely eradicate the infection, I bet you'll take it. Even if you don't fancy the thought of living forever. There's an important point in that.

Even folks who don't much want to live forever still probably don't want to die today. Or tomorrow. Someday, perhaps, if that 'someday' is held in the abstract; some future time when things no longer seem interesting. But not today. And that's the point. A solution for aging puts the power to choose in your hands. Old age forces your hand; you don't get the choice to see your grandkids graduate from school, or to celebrate your fiftieth anniversary. The choice is made for you. And I don't see how that benefits anyone."

Growing Blood Vessels (July 21 2008) http://news.bbc.co.uk/2/hi/health/7514317.stm
Researchers continue to work at the blood vessel problem in tissue engineering. From the BBC: "Scientists have used human cells to grow new blood vessels in a mouse for the first time. The ability to develop swiftly a new network of tiny blood vessels - known as capillaries - would be a prize for scientists. There are dozens of potential applications in medicine, particularly in the treatment of conditions which involve damage to a tissue's blood supply, such as that to the heart muscle following a heart attack. However, the complex structure of these vessels has slowed progress. What's really significant about our study is that we are using human cells that can be obtained from blood or bone marrow rather than removing and using fully developed blood vessels. It could certainly assist in the connection of other engineered organs to the body's blood supply. Although this approach is not yet suitable for clinical use, it is interesting that they have demonstrated you have all the elements you need to create a functional network of capillaries from a small amount of blood."
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DISCLAIMER: News summaries are reported by third parties, and there is no guarantee of accuracy. This newsletter is not meant to substitute for your personal due diligence and is not to be taken as medical advice. For originating report, please see www.longevitymeme.org/newsletter/.

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Biological Evolution

posted on July 24, 2008

We’ve come a long way in our lifetimes. In fact, we have accomplished as much then as we did in all of recorded history. At least technologically. As a race, we really didn’t seem to have learned many lessons. Oh sure, maybe our justice systems are a little more fair (and maybe not), we may have developed a little more tolerance and compassion, and maybe we’re not quite as barbaric. All in all though, we react to intrusions about the same as prehistoric man.
We still settle disputes and differences about the same way. We either initiate or answer with violence for the most part. But instead of clubbing each other senseless and confining our rage, jealousies, pettiness and intolerances to an area roughly equivalent to our immediate reach and to one enemy or victim at a time, we now have these wonders of science at our disposal, capable of inflicting widespread death and destruction.
Then, we had clubs and primitive minds. Now we have nukes, biological and chemical weapons, potentially devastating nanotechnology capabilities… and primitive minds.
While we have evolved in some ways at light speed, our ability to solve social problems and disputes and our tendency to hate hasn’t changed since caveman days. Look, we’re on the cusp of breaking through to indefinite lifespans and solutions for health problems, poverty and pollution. But what good does it do us when emotionally unstable individuals have abilities to wipe out millions with no more effort or forethought than swinging a club?
Fortunately, the human race is extremely resilient and resourceful. We often respond to challenges in creative and unexpected ways. A relatively new foundation recognizes this challenge and is taking it on as part of its agenda. See more information at www.InnerSpaceFoundation.org.
They recognize that biological evolution is a somewhat haphazard and non-optimizing process that has produced many undesirable artifacts. Among a large number and wide variety of such artifacts, two stand out as the underlying causes of the most pervasive and extreme human suffering: mental and lifespan limitations. Mental inabilities, including the failure to resolve conflicts non-violently, are universal. They must ultimately serve to explain our ongoing failures to end human warfare, crime, poverty, and famine, and to completely cure diseases, disabilities, aging and death. Therefore, these inabilities are fundamentally even more harmful to humanity than the categories of biomedical dysfunction we currently labor to cure.
This belief forms the core of the Bioprogressive philosophy. The overall goal of the InnerSpace Foundation (IF) is to accelerate developing biomedical technologies for transcending these limitations. IF is taking specific steps toward enhancing memory, learning and cognition. These near-term goals should ultimately help us to eliminate or transcend other unwanted artifacts of Darwinian evolution.
IF, among others, have longer-term goals aimed at preserving memories. So hang on. We have some interesting times ahead.
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CANCER AND IMMUNE SYSTEM PROFICIENCY

Are some immune systems much better than others at destroying cancer in its earliest stages? It seems that this is the case. Can we copy that proficiency and use it as a therapy? The prospects look promising:

http://www.fightaging.org/archives/001525.php

"First, we had cancer-resistant mice and asked, 'What can we learn from it?' The reason it's resistant is because it has very different white cells. So then that immediately prompted the concept of therapy, because you can easily transfer white cells. You can extract them as a therapeutic agent and give them to another mouse. It's a therapy. It's much better than to find the gene. If you find the gene, then you have to understand the mechanism, and you have to find a way to put the gene into the cell, into all the cells you want to, and that would not work very easily. The technology as we speak right now is not really mature for that area. You might have to wait another 10, 20 years before that technology catches up with the concept. However, what we found is a cell as a therapeutic agent, so why not go ahead and see how it works. It worked really well in mice, so the next question, very obviously, is can we find a similar cancer resistance for humans as a donor for a therapeutic agent. And the answer is yes, we did find quite a few of them ".

From a broad assessment of cutting edge cancer research, it seems that we are well on the way to turning cancer into a controllable chronic illness. You'll have outbreaks, they'll be caught early, and the medicine of the 2020s will eliminate them. The question is whether this is good enough: is a comprehensive suite of low-risk, safe cancer cures enough to remove cancer as a threat while our lives are extended by other medical technologies?
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LATEST HEALTHY LIFE EXTENSION HEADLINES

The Broadening Search for Longevity Genes (July 17 2008)
http://www.technologyreview.com/printer_friendly_article.aspx?id=21092
The MIT Technology Review looks at continued attempts to understand the degree to which present healthy human longevity is influenced by genes: "An ambitious plan to sequence 100 genes in 1,000 healthy old people could shed light on genetic variations that insulate some people from the ailments of aging, including heart disease, cancer, and diabetes, allowing them to live a healthy life into their eighties and beyond. Rather than focusing on genetic variations that increase risk for disease, scientists plan to focus on genes that have previously been linked to health and longevity. Advances in genetic screening technologies have allowed scientists to start searching the genome for clues to healthy aging and a lengthy life span. That work has revealed that the genomes of healthy old people are not blemish free. These people have genetic susceptibility markers for many serious diseases [but] they don't get any of these diseases. What is the explanation? What might account for their insulation from these diseases?" Genes are not fate - evidence to date suggests that lifestyle choices have much more weight for all but the most genetically unlucky, and those choices are reflected in epigenetic variations, not genetic variations.

Self-Assembly in Tissue Engineering (July 16 2008) http://www.technologyreview.com/printer_friendly_article.aspx?id=21080
The MIT Technology Review looks at a promising strategy in tissue engineering: "Tissue engineers are ambitious. If they had their way, a dialysis patient could receive a new kidney made in the lab from his own cells, instead of waiting for a donor organ that his immune system might reject. Likewise, a diabetic could, with grafts of lab-made pancreatic tissue, be given the ability to make insulin again. But tissue engineering has stalled in part because bioengineers haven't been able to replicate the structural complexity of human tissues. Now researchers have taken an important first step toward building complex tissues from the bottom up by creating what they call living Legos. These building blocks, biofriendly gels of various shapes studded with cells, can self-assemble into complex structures resembling those found in tissues. This will be an effective way to put the cells where we want them to be. You can probably generate a tissue with a higher complexity [using] the new method than is possible with a scaffold that has to be seeded with cells." Compare and contrast with the use of whole-organ cell matrix templates, another recent development aimed at solving the same problem.

Stress, Cortisol, and Shortened Telomeres (July 16 2008) http://www.eurekalert.org/pub_releases/2008-07/uoc--usi071508.php
Chronic stress correlates with shorter telomeres, as well as with worse health. Via EurekAlert! researchers are proposing a mechanism by which telomere length is reduced by stress, leading to a worse immune response: "Short telomeres are linked to a range of human diseases, including HIV, osteoporosis, heart disease and aging. An enzyme [called telomerase] keeps immune cells young by preserving their telomere length and ability to continue dividing. The stress hormone cortisol suppresses immune cells' ability to activate their telomerase. This may explain why the cells of persons under chronic stress have shorter telomeres. When the body is under stress, it boosts production of cortisol to support a 'fight or flight' response. If the hormone remains elevated in the bloodstream for long periods of time, though, it wears down the immune system. We are testing therapeutic ways of enhancing telomerase levels to help the immune system ward off cortisol's effect. If we're successful, one day a pill may exist to strengthen the immune system's ability to weather chronic emotional stress."

Why Fight Aging? (July 15 2008)
http://www.acceleratingfuture.com/people-blog/?p=2307
A Future Current transcript of one of Aubrey de Grey's presentations at Aging 2008: "Some people say, 'I don't want to live to a thousand.' I don't want to live to a thousand, necessarily. I don't even know if I want to live to a hundred. But I do know I want to make that choice when I am 99, rather than having it gradually removed from me by declining health. This is what it comes down to. The extension of lifespan by the defeat of aging is not the point - at least it is not the main point for me, and I do not think it is the main point for most people who are engaged in this crusade. The purpose is to alleviate the suffering that goes with getting decrepit, frail and dependent. Of course, this includes not just those who are suffering that, but the suffering of their loved ones. The extension of average lifespan is essentially a side benefit. It is something that will happen because the way that we are going to do this, using regenerative medicine, will also mean that you have only the same probability you did when you were a young adult of dying peacefully in your sleep without any of these diseases. In other words, a very low probability indeed. You will indeed on average live a great deal longer, and I don't think you’ll complain if you do. However, that is not the purpose. The purpose is to alleviate suffering."

On the Way to Longevity (July 14 2008)
http://www.dailybruin.ucla.edu/news/2008/jul/14/within-20-years-you-wont-have-grow-old/

The Daily Bruin talks to some of the folk who were at Aging 2008: "Defeating the effects of time by finding a cure for aging has become the focus of multiple areas of research, bringing the possibilities of achieving immortality from fantasy into the realm of science. The new possibilities offered by regenerative medicine illustrate how advancements in therapy on the molecular and cellular level may be able to extend the healthy human life span within the next 20 years. Finding a cure for aging is no longer a theoretical target or a fantasy, but on the way to becoming a practical target. Aging is the most universal degenerative condition and is now becoming the target of regenerative medicine. The body is a really complicated machine, but it's still a machine, so its healthy lifespan can be extended indefinitely by sufficiently comprehensive repair and maintenance, just like simple man-made machines. Aging is a complex phenomenon that affects many different systems. Understanding it and fixing the damage as it comes can potentially cure the harmful effects of aging and as a result, elongate the healthy human lifespan." Back to Top

Can Super Longevity Solve the Population Problem?

posted on July 14, 2008

Consider these points edited from a paper presented several weeks ago by Herb Meyer at the World Economic Forum in Davos, Switzerland. Mr. Meyer is widely credited with being the first senior U.S. Government official to forecast the Soviet Union's collapse, for which he later was awarded the U.S. National Intelligence Distinguished Service Medal, the intelligence community's highest honor. Formerly an associate editor of FORTUNE, he is also the author of several books.

Some of His Conclusions

Maintaining a steady population requires a birth rate of 2.1. In Western Europe, the birth rate currently stands at 1.5, or 30 percent below replacement. In 30 years there will be 70 to 80 million fewer Europeans than there are today. The current birth rate in Germany is 1.3. Italy and Spain are even lower at 1.2. At that rate, the working age population declines by 30 percent in 20 years, which has a huge impact on the economy. When you don't have young workers to replace the older ones, you have to import them.

In Japan, the birthrate is 1.3. As a result, Japan will lose up to 60 million people over the next 30 years. Because Japan has a very different society than Europe, they refuse to import workers. Instead, they are just shutting down. Japan has already closed 2,000 schools, and is closing them down at the rate of 300 per year. Japan is also aging very rapidly. By 2020, one out of every five Japanese will be at least 70 years old.

The birth rate in Russia is so low that by 2050 their population will be smaller than that of Yemen.

Nobody has any idea about how to run an economy with those demographics. Europe and Japan, which comprise two of the world's major economic engines, aren't merely in recession, they're shutting down. This will have a huge impact on the world economy, and it is already beginning to happen.

When the birth rate drops below replacement, the population ages. With fewer working people to support more retired people, it puts a crushing tax burden on the smaller group of working age people. As a result, young people delay marriage and having a family. Once this trend starts, the downward spiral only gets worse.

These countries have abandoned all the traditions they formerly held in regard to having families and raising children. The U.S. birth rate is 2.0, just below replacement. We have an increase in population because of immigration. When broken down by ethnicity, the Anglo birth rate is 1.6 (same as France) while the Hispanic birth rate is 2.7.

In the U.S., the baby boomers are starting to retire in massive numbers. This will push the elder dependency ratio from 19 to 38 over the next 10 to 15 years. This is not as bad as Europe, but still represents the same kind of trend.

The world's most effective birth control device is money. As society creates a middle class and women move into the workforce, birth rates drop. Having large families is incompatible with middle class living. The quickest way to drop the birth rate is through rapid economic development.

NOTE: Pretty sobering, isn’t it? So what’s the solution? Longevity… and lots of it. Keep the elderly alive, healthy and productive. Keep them out of retirement, hospitals and nursing homes where they drain resources, and have them contribute to the economy when they are at the peak of their productive capacity.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

Sonia Arrison on Aging 2008 (July 11 2008) http://www.technewsworld.com/story/Technology-and-the-Aspiring-Methuselahs-63748.html?welcome=1215782396
From TechNewsWorld: "More than 200 scientists and longevity activists gathered at UCLA recently to discuss advancements in repairing humans. New technology is making it possible to imagine a world with ever greater life spans, but old world issues pervaded the discussions. 'We should mount a war on aging where it is not a disease, it is THE disease,' said Gregory Stock, Ph.D., director of the UCLA Program on Medicine, Technology and Society. To do this, Stock proposed an 'aggressive publicly funded program.' While no one challenged this idea on the panel, during the two days of the conference, it was clear that some questioned the efficacy of such a plan. Indeed, in a less formal setting, [Bruce] Ames lamented the fact that under the mostly government-run system of science grants, the 'true visionaries are not getting funding.' This is not surprising, given that government agencies are by nature political, making decisions with an eye toward public opinion, not necessarily the best and brightest ideas. Agencies like the U.S. National Institutes of Health and particularly the Food and Drug Administration typically become risk averse over time, as it's easier to deny approval for an idea or product that no one ever finds out about than it is to take a chance on a revolutionary idea and have it flop."

AGEs and DNA Damage? (July 10 2008) http://www.eurekalert.org/pub_releases/2008-07/esfh-dlt070808.php
A research group is proposing that buildup of advanced glycation end-products (AGEs) causes DNA damage in addition to known other issues: "The scientists studied semen samples from men with diabetes who were receiving insulin therapy. When we looked for DNA damage, we saw a very different picture. Sperm RNA was significantly altered, and many of the changes we observed are in RNA transcripts involved in DNA repair. Diabetics have a significant decrease in their ability to repair sperm DNA, and once this is damaged it cannot be restored. We found a class of compounds known as advanced glycation end products (AGEs) in the male reproductive tract. These [accumulate] during normal aging. They are dependent on life style - diet, smoking etc - and in many diabetic complications are centrally implicated in DNA damage. ... The scientists intend to follow up their work by trying to determine how AGEs cause and contribute to DNA damage. They believe that they may have uncovered a new role for AGEs, and that their influence goes far beyond diabetes and its complications." I think that this is proposed on a fairly weak correlation, but we'll see where it goes.

The Longevity Dividend Message (July 09 2008) http://www.eurekalert.org/pub_releases/2008-07/uoia-ess070708.php
Via EurekAlert!, advocacy from those who believe that engineering metabolism to slow the accumulation of age-related damage is the only way ahead: "The traditional medical approach of attacking individual diseases -- cancer, diabetes, heart disease, Alzheimer's disease and Parkinson's disease -- will soon become less effective if we do not determine how all of these diseases either interact or share common mechanisms with aging. All living things, including humans, possess biochemical mechanisms that influence how quickly we age and, through dietary intervention or genetic alteration, it is possible to extend lifespan to postpone aging-related processes and diseases. We believe that the potential benefits of slowing aging processes have been underrecognized by most of the scientific community. We call on the health-research decision-makers to allocate substantial resources to support and develop practical interventions that slow aging in people." Meanwhile, initiatives to raise funding to develop the means to repair - rather than just slow - the damage of aging continue. I believe those initiatives to be the superior path forward, as they seem likely to be less complex, less costly, and more effective.

MSNBC on Calorie Restriction (July 09 2008) http://www.msnbc.msn.com/id/25588227/
How far we've come in the past five years, from the days in which the mainstream media poured scorn on the practice of calorie restriction. If there is a lesson here, it is to observe the way in which the Calorie Restriction Society engaged and encouraged the research community: progress in science is a necessary accompanyment to progress in advocacy for a cause. From MSNBC: "While the quest for the proverbial Fountain of Youth is endless and typically fruitless, one method known to extend the human lifespan by up to five years has quietly become accepted among leading researchers. The formula is simple: Eat less. It could add years to your life, several experts now say. And done in moderation, it could at least help you live a more healthy life. The only question is: Will the average person do it? Here's a rough rule of thumb that many experts generally agree on now: Eat 15 percent less starting at age 25 and you might add 4.5 years to your life. Eating fewer calories also reduces age-related chronic diseases such as cancers, heart disease, and stroke in rodents. That's important because it suggests ways to not just make us live longer, but to allow us to age more gracefully, healthwise."

FuturePundit on Resveratrol Results (July 07 2008) http://www.futurepundit.com/archives/005336.html
FuturePundit comments on the latest resveratrol research: "Surprisingly, resveratrol extends life of those on the calorie restriction diet. I say 'surprisingly' because calorie restriction is already causing most of the changes that resveratrol causes. But note that mice on the middle range calorie diet did not live longer as a result of resveratrol treatment. Maybe on the [every other day feeding] mice the resveratrol worked by mimicking the effects of calorie restriction on the feeding days? My reaction to this study is mild disappointment. Resveratrol did not work nearly as well as calorie restriction in extending life. You still need to starve yourself to assure a longer life." It's convenient verbal shorthand, but the practice of calorie restriction is not "starving yourself." It's important to be correct in these matters - calorie restriction is elimination of calories above those needed to be healthy, while still obtaining an optimal level of micronutrients. Many slim, healthy people are already practicing a form of mild calorie restriction when measured against commonly recommended dietary intake. Still, my fervent hope is that calorie restriction will become irrelevant and outstripped by the first medical interventions to extend healthy life, hopefully within the next 20 years.
My money is on technologies of mitochondrial replacement.

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A Real Boost for Aging Research

posted on July 7, 2008

Friday, June 27th I attended Aging 2008 - Aging: the Disease, the Cure, the Implications at UCLA. It was sponsored by Dr. Aubrey de Grey and the Methuselah Foundation. About 700 people attended a stimulating three hour session featuring an All-Star lineup of aging researchers, advocates and personalities.

Most of the attendees spent the next couple of hours networking at an outdoor dinner. In my opinion, some of the more important and interesting people in the world were there, including some movers and shakers who are launching exciting companies and research projects – projects that could have a big impact on your health and longevity.

Here is a list of the speakers:

Dr. Bruce Ames, Professor of Biochemistry and Molecular Biology at UC Berkeley
G. Steven Burrill, Chairman of Pharmasset and Chairman of Campaign for Medical Research
Dr. Aubrey de Grey, Chairman and CSO of Methuselah Foundation and author of Ending Aging
Dr. William Haseltine, Chairman of Haseltine Global Health
Daniel Perry, Executive Director of Alliance for Aging Research
Bernard Siegel, Executive Director of Genetics Policy Institute
Dr. Gregory Stock, Director of Program on Medicine, Technology & Society at UCLA School of Medicine
Dr. Michael West, CEO of BioTime and Adjunct Professor of Bioengineering at UC Berkeley

I also got a Methuselah Foundation T-shirt, one of the coolest T-shirts I ever saw.

Aging 2008 was the opening session for the technically focused Understanding Aging conference which took place Saturday and Sunday. Thirty four scientists presented over the weekend. I believe this was the most extensive scientific longevity conference ever held in the US. Hopefully, the Methuselah Foundation will offer videos.

Open-forum events like this enable scientists to bounce ideas of one another, to cross pollinate ideas and to open up various research programs to debate and scrutiny. As a result, it fast tracks longevity research. Congratulations to Aubrey de Grey and all the Methuselah Foundation volunteers who made it happen.

Then last week, I attended a presentation to an investment banker to fund two very progressive adult stem cell companies. He made a verbal commitment, and funding might take place as early as this month. Once these companies are launched, human therapies could be accelerated. That could translate to the first round of therapies becoming available by next year. Anti-aging science is ratcheted up one more notch.

All-in-all that was a very productive week for life extension. Let’s look forward to many more.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

Surprise, Surprise (July 04 2008) http://www.phgfoundation.org/news/4263/
From the PHG Foundation: "a new publication in the journal Cell Stem Cell has claimed that countries with less restrictive regulatory regimes account for a disproportionately high level of scientific publications, supporting concerns cited by many prominent US researchers that without easing of current legislation such as current restrictions on the use of federal funding for stem cell research [the] country will lag behind in this area of medicine. Countries dubbed 'overperforming' in stem cell publications were Singapore, the UK, Israel, China and Australia, while 'underperformers' included the US, Japan, France and Switzerland. The author concludes that the most highly performing countries had generally permissive policy environments for [embryonic stem cell] research, whilst those lagging behind were characterized by 'protracted policy debates and ongoing uncertainty, regardless of their current policy environment'." No great shock there. The more you make it hard to move forward, the less moving forward there will be. This has little to do with degrees of public funding, and everything to do with levels of regulation.

The Bionic Human Checklist (July 04 2008) http://technology.newscientist.com/article/dn14256-do-we-have-the-technology-to-build-a-bionic-human.html
We're a fair way from being able to produce a complete replacement for the functions of human body - a very sane goal if you'd like to live a lot longer - but the checklist of what can be replaced is getting longer by the month. From the New Scientist: "More and more of the body is becoming, if not obsolete, then certainly replaceable. But which of our body parts can be engineered today, and which will we have to make do with? Implants that copy the simple structural job of skeletal tissue are the easiest to build. By culturing normal or stem cells it is now possible to grow pretty much any type of tissue. Some complete organs have already been grown from scratch. Other parts of the body's plumbing network, such as the lymphatic system, are becoming replaceable too. Last year, mice were implanted with an artificial lymph node made from collagen and cells taken from a gland in newborn mice. Implants can also help the blind see, by stimulating the retina, optic nerve or the brain's visual cortex. Other research seeks to replace entire limbs with robotic replacements."

Ouroboros on Michael Rose's SENSE (July 03 2008) http://ouroboros.wordpress.com/2008/07/02/evolutionary-theories-of-aging-as-applied-to-lifespan-extension/
Over at Ouroboros, comments on SENSE, Michael Rose's consideration of his research as it impacts the "repair damage to cure aging" viewpoint of the Strategies for Engineered Negligible Senescence (SENS): "Rose concludes that life-extension therapeutics must address the issue of age-specific adaptation in order to be effective. In the evolutionary view, increasing risk of mortality is the consequence of a failure to adapt to the selection-pressure landscape specific to a particular age; because post-reproductive lifespan is largely (but not always) masked from selection, it is easy to see how such age-specific failures of adaptation might occur. The 'mortality plateaus' to which the author refers are life-history periods of constant, rather than increasing, mortality risk. Rose argues that the existence of these plateaus in the survival curves of many species imply that accumulation of irreparable damage is - at the very least - not the whole cause of aging. Therefore, the argument goes, reversing this damage cannot be sufficient to prevent or reverse aging as such."

Resveratrol in Normal Mice (July 03 2008) http://www.eurekalert.org/pub_releases/2008-07/nioa-rft062708.php
From EurekAlert!: "Scientists have found that the compound resveratrol slows age-related deterioration and functional decline of mice on a standard diet, but does not increase longevity when started at middle age. Dietary restriction has well-documented health benefits in mammals, and the study of possible mimetics of it, such as resveratrol, are of great interest. Resveratrol did not have a significant effect on lifespan in animals fed standard chow, suggesting that the intervention di