Intestinal Bacteria and Ageing
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In light of recent research into the effects of calorie restriction on those little plants and animals that live in your gut, this would seem interesting: "The intestinal microbiota is important for maintenance of host health, providing energy, nutrients and protection against invading organisms. Although the colonic microbiota is relatively stable throughout adult life, age-related changes in the gastrointestinal (GI) tract, as well as changes in diet and host immune system reactivity, inevitably affect population composition. Recent studies indicate shifts in the composition of the intestinal microbiota, which may lead to detrimental effects for the elderly host ... These changes, along with a general reduction in species diversity in most bacterial groups, and changes to diet and digestive physiology such as intestinal transit time, may result in increased putrefaction in the colon and a greater susceptibility to disease. Therapeutic strategies to counteract these changes have been suggested in ageing people." Will this turn out to have as much of an effect on healthy longevity as, say, exercise or calorie restriction? Possibly, you never know. Invariably, these line items pale before the future of longevity science, however - stay focused on the big picture.

Link: http://dx.doi.org/10.1111/j.1365-2672.2007.03400.x

How Autologous Stem Cell Therapies Work
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How is it that autologous stem cell therapies work? From ScienceDaily: new work is "shedding light on the previously mysterious mechanism through which even relatively small amounts of stem/progenitor cells taken from a patient's own bone marrow enhance repair of damaged tissues. ... The cells not only differentiate to replace injured cells, as had been understood, but they also stimulate the proliferation and differentiation of stem cells already present in the injured tissue and they transfer mitochondrial DNA to local cells in which the mitochondria (the energy of the cell) is not working. Better understanding of the different mechanisms of these stem/progenitor cells suggests multiple strategies for developing new therapies for a broad range of diseases. ... the studies are explaining the mechanisms by which the cells work, in animals and in the more than 1,000 cardiovascular and other patients in the United States believed to be enrolled in clinical trials using these cells taken from their bone marrow." The mitochondrial transfer is certainly interesting. Could we make inroads in repairing age-damaged mitochondria via the application of stem cells in addition to the more obvious methods?

Link: http://www.sciencedaily.com/releases/2007/04/070429170640.htm

Science That Fell Into My Path Today
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In lieu of any more coherent message, I though I'd point out some items of interest that attracted my attention today. They all illustrate the great long term value inherent in understanding of biochemical mechanisms; we are at the stage now where understanding can quickly lead to therapies and potential cures for those conditions with more straightforward causes. One might even argue that, given enough progress and knowledge, all causes become straightforward. The moon and stars were mysteries until they were not; the same is true of the detailed molecular workings of our bodies.

The Role of Cellular Senescence in Werner Syndrome:

Werner syndrome (WS) is a premature aging disorder used as a model of normal human aging. WS individuals have several characteristics of normal aging, such as cataracts, hair graying, and skin aging, but manifest these at an early age. Additionally, WS individuals have high levels of inflammatory diseases, such as atherosclerosis and type 2 diabetes. The in vivo aging in WS is associated with accelerated aging of fibroblasts in culture. The cause of the accelerated senescence is not understood, but may be due to the genomic instability that is a hallmark of WS. Genome instability results in activation of stress kinases, such as p38 ... The recent development of p38 inhibitors with different binding properties, specificities, and oral bioavailability [will] make it possible to dissect the roles of various kinase pathways in the accelerated senescence of WS cells. If this accelerated senescence is reflective of WS aging in vivo, these kinase inhibitors may well form the basis of antiaging therapies for individuals with WS.

As has been observed for progeria, Werner syndrome appears to result from one contributing mechanism of normal aging grown wild and exaggerated. As for progeria, it seems plausible that therapies for Werner syndome will have at least some value for those of us fortunate to "only" be aging normally.

Effects of Deleting Mitochondrial Antioxidant Genes on Life Span:

Reactive oxygen species (ROS) damage biomolecules, accelerate aging, and shorten life span, whereas antioxidant enzymes mitigate these effects. Because mitochondria are a primary site of ROS generation and also a primary target of ROS attack, they have become a major focus area of aging studies. Here, we employed yeast genetics to identify mitochondrial antioxidant genes that are important for replicative life span.

Of the ten known genes, only three made much difference - interesting. If you want to bioengineer mitochondria to produce more antioxidants of those types already produced, it makes sense to focus on those that make the most difference. Small steps on a long road ahead.

Alzheimer’s, Parkinson’s, Type II Diabetes Are Similar at the Molecular Level

Alzheimer's disease, Parkinson's disease, type II diabetes, the human version of mad cow disease and other degenerative diseases are more closely related at the molecular level than many scientists realized ... Harmful rope-like structures known as amyloid fibrils, which are linked protein molecules that form in the brains of patients with these diseases, contain a stack of water-tight "molecular zippers," the scientists report.

"We have shown that the fibrils have a common atomic-level structure," said David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics, a Howard Hughes Medical Institute investigator and a member of the research team. "All of these diseases are similar at the molecular level; all of them have a dry steric zipper. With each disease, a different protein transforms into amyloid fibrils, but the proteins are very similar at the atomic level."

The research, while still preliminary, could help scientists develop tools for diagnosing these diseases and, potentially, for treating them through "structure-based drug design," said Eisenberg, a UCLA professor of chemistry and molecular biology.

Drug design will increasingly become a matter of molecule design in the years ahead. Researchers are looking for atomic-scale glue, levers, patches and prybars to pick apart, block or reshape disease-causing arrangements of molecules - which of course requires a good knowledge of what all these molecules are actually doing in the first place. Aging itself is nothing more than an undesirable rearrangement of molecules; if we want to effectively deal with aging, then we're going to have to become very good at this sort of thing.

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On Comments and the Management Thereof
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How do I manage comments at Fight Aging! - what is my policy? Well, first off, I don't have a "policy," as such. But let me describe the sort of response a comment will elicit from the combination of this publishing software and my review.

  • All comments are moderated by the software. It's the only way to keep things absolutely clean, but it does mean there will be a delay in posting, usually a matter of hours. Conversations in the comments here at Fight Aging! tend to happen across days, so pace yourself accordingly.

  • Spam is deleted, mostly by the software and occasionally by me. For what it's worth. It's easy to tell what is and isn't spam, but those putting it out will never read this post to see just how pointless their efforts are. It's a waste of everyone's time, but the faceless spammers of the world aren't going to stop anytime soon. It's easier to spam as broadly as possible rather than show any selectivity based upon results.

  • The more subtle human-mediated forms of spam, such as link-fishing, are dealt with on a case by case basis. If your comment is interesting and relevant, but festooned with links to odious locations, it might be left as is minus the links. Again, it really is easy to tell the difference between spam and a legitimate comment of value; trying to put one past someone who knows the topic is a waste of everyone's time.

  • If you're fishing for links back to your blog - your real, actual blog, containing real, actual, interesting content - then this is the way it goes: valuable and relevant comments buy you the right to keep your link. Trivial or repetitive comments do not.

  • Legitimate and helpful comments bearing many links might take longer to clear through moderation; they sometimes end up in the spam bucket and need fishing out. This takes longer than a simple approval.

  • I don't like it when folk link to or advocate commercial products in the comments. Discuss by all means, but don't hawk the stuff. At some point, such as for threads on protandim and resveratrol, I get tired of repeating myself on that point and close the post to further comments. Even though all comment links are marked as "nofollow," those links still benefit the recipients in a number of ways. Not all search engines respect the nofollow standard, and in most cases those who add links are looking for clickthroughs rather than enhancing their relevance in Google or similar places.

  • Ad hominem attacks and general unpleasantness are mostly likely going to be deleted. There's more than enough of that back in meatspace. No need to bring it here with you.

  • Utterly irrelevant or otherwise strange comments ("I like fish!") are also bound for the deletion bin. Fascinating no doubt, but not here please.

  • People occasionally post requests for information, or messages to various people in the comments. I usually delete these and respond via email if the request merits a response. Many do not. Requests to pass messages on to person X, Y or Z, for example, will usually just be deleted - in this day and age of the internet, it isn't hard to get in touch directly, or get out there and do a little research. Make the effort.

So, basically, don't be a jerk and don't try to make blatant hay from the existence of Fight Aging! Other than that, have fun and be constructive.

Exercise Versus Parkinson's
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Health 24 reports that an analysis of the data from a large cancer study suggests that exercise helps lower the risk of Parkinson's disease: "The researchers looked at exercise levels and tried to determine if they affected the rate of Parkinson's disease after adjusting the numbers to reflect the possible influence of factors such as age, gender and smoking. People who exercised more than 75 percent of their fellow study participants were 20 percent less likely to develop Parkinson's, compared to those who didn't exercise. The risk of the disease was 40 percent lower in those who took part in the highest levels of moderate to vigorous activity, defined as exercise such as jogging, lap swimming, tennis and bicycling, the study found." This sort of analysis is never as robust as the results of a study specifically designed to produce the data you're after, so treat with caution. We already know that exercise is strongly correlated with resistance to most common age-related conditions, however. It's almost as good as calorie restriction! Even if Parkinson's isn't one of these conditions, that's no reason to skimp on keeping up with the health basics.

Link: http://www.health24.com/news/Brain_Neurological/1-896,40170.asp

Changing Cancer Cells Back Into Normal Cells
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One logical outgrowth of the quest to control cell state as a part of regenerative medicine is an initiative to control the state of cancerous cells. From EurekAlert!: researchers "discovered that aggressive melanoma cells (but not normal skin cells nor less aggressive melanoma cells) contain specific proteins similar to those found in embryonic stem cells. This groundbreaking work led to the first molecular classification of malignant melanoma and may help to explain how, by becoming more like unspecialized stem cells, the aggressive melanoma cell gained enhanced abilities to migrate, invade and metastasize while virtually undetected by the immune system. ... Embryonic stem cells are pluripotent, meaning they are able to differentiate into any of the more than 200 cell types in the adult body. Which type of cell they become depends on the signals they receive from their microenvironment. Similarly, during cancer progression, malignant cells receive and release signals from their own microenvironment, cues that promote tumor growth and metastasis. ... scientists can change human metastatic melanoma cells back to normal-like skin cells - by exposing the tumor cells to the embryonic microenvironment of human embryonic stem cells."

Link: http://www.eurekalert.org/pub_releases/2007-04/nu-rcc042507.php

More Support For the Merits of Starting Calorie Restriction Late
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If you haven't been practicing calorie restriction for most of your life, there's not a lot you can do (yet) about the irreversible damage done to your body so far - broken molecules and broken systems that cannot be repaired naturally. Aging is nothing more than the consequences of that irreversible damage, and you've been accumulating it faster than you might have been. That's past and done now. Still, it appears that adopting calorie restriction even late in life brings meaningful benefits:

Physiological changes associated with ageing include cell damage and the emergence of cancer cells. The most important effects of low calorie diets and longevity therapeutics given late in life may not be to prevent this damage, but instead to stimulate the body to eliminate damaged cells that may become cancerous, and to stimulate repair in damaged cells like neurons and heart cells. Low calorie diets drive the body to replace and repair damaged cells. This process usually slows down as we age, but low calorie diets make the body re-synthesise and turn over more cells - a situation associated with youth and good health.

No-one wants to develop cancer any sooner, or have their body run down years before it might; even if you've led the life of a gourmand up until now, why not look into calorie restriction? I noticed another report of basic research that lends a little more support to the position stated above:

Beneficial Biochemical Outcomes of Late-Onset Dietary Restriction in Rodents:

Dietary restriction (DR) or caloric restriction (CR) is the well-established means to retard aging, leading to prolongation of mean and maximum life span in many animal models. We have been interested in the possibility of extending the span of health of elderly people rather than increasing longevity, and therefore studied the effects of DR/CR initiated late in life in rodent models. We restricted food for 2-3.5 months in mice or rats of middle or old ages, which would perhaps be equivalent to 50-70 years of age in humans. We found that: (1) Potentially harmful altered proteins were reduced in the animals' tissues. (2) Extended half-life of protein in aged animals was shortened in mouse hepatocytes, suggesting improved protein turnover. (3) Reduced proteasome activity was upregulated in rat liver and skeletal muscle. (4) Protein carbonyls were decreased in rat liver mitochondria and skeletal muscle cytoplasm, and also oxidative DNA damage was reduced in rat liver nucleus, suggesting amelioration of oxidative stress. (5) Reduced apo A-IV and C-III metabolism in aged mouse was restored, suggesting increase in reduced fatty acid mobilization. (6) The carbonyl modification in histones that was paradoxically reduced in aged rat was increased to the level of a young animal, suggesting restoration of reduced transcription. These findings in rodents suggest a possibility that DR/CR is beneficial if applied in middle-aged or early senescent obese people. We argue, however, that application of late life DR/CR can be harmful if practiced in people who are already eating modestly.

It is interesting that the authors put that last disclaimer into the abstract, given the rest of the material in the paper and the evidence from human studies to date. It echos their position from the opening statement, the very mainstream characteristic of denying any desire to enhance longevity for fear of prejudicing future grant applications. The culture of gerontology has required people to hide behind the goal of extending healthy life in the aged without extending longevity - a goal the Reliability Theory of Aging and Longevity suggests is impossible - and ultimately led to a generation of scientists who bought into and believed this view. By doing so they would never support or work on science likely to actually extend healthy longevity in any significant way. Fortunately, this sort of thing becoming less common, as the campaign for increased support for deliberate efforts to extend healthy life spans continues, but you're still going to see it here and there.

But back to calorie restriction: the evidence for its benefits really are overwhelming. So much so that venture capitalists and other funding organizations are willing to sink hundreds of millions of dollars into producing knowledge and drugs that may have some of the same effects. Is eating less with optimal nutrition worth further investigation on your part? If you enjoy being alive and healthy to enjoy it, then very much so.

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Common Sense on Extending Healthy Longevity
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A dose of common sense from calorie restriction (CR) practioner April Smith: "First, no one I know thinks that true immortality is a possibility. There will always be accidents ... However, there are some very reasonable people who believe that it is possible that technology will advance enough to defeat many of the mechanisms that cause aging. If we could repair the damage of aging, then we could dramatically extend life and health. I believe that would be a very good thing. ... Before I got involved in the CR Society, I wasn't aware that these perspectives existed. I was hopeful that CR could help me look forty at fifty-five, or at least help me not feel like total crap at 29, but I didn't even think about radical life-extending biomedicine. ... but there are quite a few who hope that by pursuing vigorous CR, we might live and be in good health at a time when more advanced medical technologies are available to extend healthy life further. For those who dismiss this as childish fantasy, I ask on what basis they make that determination. ... I can attest that I was quite unaware of the real progress that has been made in recent years, and when I found out more, my perspective changed."

Link: http://www.mprize.org/blogs/archives/2007/04/unusual_means_t.html

What Happened To the Point of the Exercise?
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An interesting position paper from Aubrey de Grey via the Annals of the NYAS: "The early days of biogerontology were blessed with an undiluted forthrightness concerning the field's ultimate goals, epitomized by its leaders. Luminaries from Pearl to Comfort to Strehler declared the desirability of eliminating aging with no more diffidence than that with which today's oncologists aver that they seek a cure for cancer. The field's subsequent retreat from this position garnered a modicum of political acceptability and public financial support, but all biogerontologists agree that this fell, and continues to fall, vastly short of the funding that the prospect of even a modest postponement of aging would logically justify. The past 20 years' discoveries of life-extending genetic manipulations in model organisms have weakened the argument that a policy of appeasement of the public's ambivalence about defeating aging is our only option; some of the biogerontologists responsible for these advances have espoused views of which our intellectual forefathers would be proud, without noticeably harming their own careers. With the recent emergence of a detailed, ambitious, but practical roadmap for the comprehensive defeat of aging, this process has moved further: our natural and most persuasive public stance is, more than ever, to reembrace the same unassailable logic that served pioneering biogerontologists perfectly well."

Link: http://dx.doi.org/10.1196/annals.1395.046

Israeli Parkinson's Research
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A glance at some of the Parkinson's research from young Israeli concerns via Globes Online: "The damaged neurons of patients suffering from Parkinson's can no longer create dopamine in the brain, thus causing the muscle tremors, rigidity and twitches that make life a nightmare for them. When given synthetically, dopamine relieves the patient's symptoms but its effect is temporal and is associated with significant side effects. Reubinoff hopes to successfully transplant these converted dopamine producing neurons into the human body, enabling the body to resume producing its own dopamine. ... While Parkinson's patients show an inflammation of the central nervous system, anti-inflammatory medication has not helped. Proneuron's research has shown that boosting the right immune system response can successfully modulate the immune activity to become beneficial for neuronal survival and renewal. This approach has the potential not only to attenuate or stop disease progression, but also to restore lost function."

Link: http://www.globes.co.il/serveen/globes/docview.asp?did=1000203499

The Cost of Just One Age-Related Condition
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Age-related degeneration is an ongoing corrosion of all our resources - for all resources spring from human action, which requires health and life. Aging costs us greatly in every way; here, EurekAlert! catalogues just one fraction of the whole: "Arthritis and other rheumatic conditions exact a large and growing economic toll on the nation as a result of the increase in numbers of persons affected, rather than an increase in mean expenditures and earnings losses ... In 2003, employed adults with arthritis earned an average of $3,613 less than healthy working adults between the ages of 18 and 64. Nationwide, raw earnings losses due to arthritis totalled $108 billion, up from $99 billion in 1997. ... Since the number arthritis sufferers is projected to increase steadily to nearly 67 million by 2030, [the] economic toll threatens to continue to escalate. He calls urgent attention to the need for cost-effective efforts to decrease medical expenses and increase the earning power of people with arthritis." This projection is a future in which we fail to support and advance medical research. The solutions proposed in the article are, as ever, second-rate, given that we're in the midst of a biotechnology revolution. The real solution to age-related disease is to push hard for cures, preventions, and real anti-aging research like SENS.

Link: http://www.eurekalert.org/pub_releases/2007-04/jws-tei042307.php

Lie Extension in Cuba
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Yes, "lie extension." No "f" involved. I rarely comment on any component of the ever present flow of nonsense written on the topic of longevity, "anti-aging," aging and so forth in the popular press. There's always some gullible fool - or journalist with a news hole to fill - out there repeating the latest absurdities as though cast in gold and sealed with a writ of absolute authority. So, of course, I haven't said anything about the matter of life expectancy and Cuba, for all that it's been in the news for a while.

However, I think it's worth noting those who take the time to point out the true nature of the Emperor's clothes:

In a widely distributed news story, the Associated Press last week explained why Cubans were living such long, healthy lives under their 47-year totalitarian dictatorship. Taking the word of Cuban officials, it credited the island's "mild climate," "free medical care" and "low-stress Caribbean lifestyle." Right on cue, CBS gave "thanks to the socialist island state's free health-care system" that's there so "fortunately."

But media claims that socialism lets Cubans live longer makes no sense. Cuba's living conditions portend anything but a long life. The media reports, moreover, often misinterpret the data. "The average Joe reading these stories doesn't have all the background, and can be fooled by propaganda," says Cuban author Humberto Fontova.

...

From sanitation to housing, "Cubans have experienced deterioration in all health indicators," Mesa-Lagos said. As a result, Cubans have seen an uptick in diseases such as hepatitis and acute diarrhea. The increase of water-borne diseases does not correlate with long life spans anywhere else in the world, he said.

Food and critical vitamin shortages, meanwhile, were also major problems in Cuba, notes Andy S. Gomez, assistant provost of the University of Miami's Institute for Cuban and Cuban-American Studies. "A deficit of Vitamin C and a lack of appropriate diet has caused Cubans to suffer eye diseases," he said.

Mesa-Lagos agreed, saying that a few years ago, elderly Cubans experienced an epidemic of sudden blindness due to vitamin shortages. Worse yet, a third of Cuban doctors had been shipped to Venezuela, leaving many with no access to any health care at all, he added.

Freedom is the root of longevity, because freedom is the root of wealth, in the broadest possible sense. Wealth is exactly technology - wealth is access to resources, and technology is the means by which new resources are made available. Life itself is a resource, forged by our actions, and freedom allows people to come together and rapidly produce that resource for all.

You'd think that knowing now exactly what horrors transpired in the former Soviet Union, people would understand what socialism really means. Socialism and other forms of jealous, centralized control form the path to poverty and suffering - they are anything but the path to longevity.

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The Consensus on Sirtuins
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From Michen and Sinclair, a look at the present consensus on sirtuins: "Sirtuins are a conserved family of proteins found in all domains of life. The first known sirtuin, Sir2 (silent information regulator 2) of Saccharomyces cerevisiae, from which the family derives its name, regulates ribosomal DNA recombination, gene silencing, DNA repair, chromosomal stability and longevity. Sir2 homologues also modulate lifespan in worms and flies, and may underlie the beneficial effects of caloric restriction, the only regimen that slows aging and extends lifespan of most classes of organism, including mammals. Sirtuins have gained considerable attention for their impact on mammalian physiology, since they may provide novel targets for treating diseases associated with aging and perhaps extend human lifespan. In this review we describe our current understanding of the biological function of the seven mammalian sirtuins, SIRT1-7, and we will also discuss their potential as mediators of caloric restriction and as pharmacological targets to delay and treat human age-related diseases."

Link: http://www.ncbi.nlm.nih.gov/pubmed/17447894

The Wrong Perspective
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A good example of absolutely the wrong way to look at what is happening in longevity and medicine can be found at Newslink: increasing longevity is "happening" and we must marshall our resources to "address" it. This is nonsense - we humans are making our own longevity, creating additional years of healthy life through investment in medical research and development. We don't need to run around babbling about society and organization and coping. Instead we should recognize that people are dying of aging in vast numbers each and every day, and that it is well within our power to make the present slow inroads into fighting aging proceed a great deal more rapidly. "While life expectancy continues to increase at its current rate, we must wake up to the fact that we are living a 29-hour day. have 24 hours to use now, and we are putting by five hours away for later." This is nothing compared to what we know to be possible in the decades ahead - but we won't get there by thinking that longevity just happens, and that longer lives must be "addressed."

Link: http://www.ncl.ac.uk/press.office/newslink/?ref=1177503543

The Keys to the Kingdom
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The keys to the kingdom of biology are numerous and small - but those are the only obstacles to obtaining control over growth, structure, disease and aging. If you have the tools to manage the small, then progress towards the end of disease and aging is only a matter of many willing hands, investment and hard work.

We humans will adapt to anything, including the stream of constantly amazing, wonderous demonstrations of medical technology arriving thick and fast in this new century. No-one is as amazed as they should be any more by the likes of this:

Nanotechnology Offers Hope for Treating Spinal Cord Injuries, Diabetes, Heart and Parkinson's Disease:

In a dramatic demonstration of what nanotechnology might achieve in regenerative medicine, paralyzed lab mice with spinal cord injuries have regained the ability to walk using their hind limbs six weeks after a simple injection of a purpose-designed nanomaterial.

...

"By injecting molecules that were designed to self-assemble into nanostructures in the spinal tissue, we have been able to rescue and regrow rapidly damaged neurons," said Dr. Stupp at an April 23 session hosted by the Project on Emerging Nanotechnologies. "The nanofibers -- thousands of times thinner than a human hair -- are the key to not only preventing the formation of harmful scar tissue which inhibits spinal cord healing, but to stimulating the body into regenerating lost or damaged cells."

Stupp's work hinges on a fundamental area of nanotechnology -- self- assembly -- that someday should enable medical researchers to tailor and deliver individualized patient treatments in previously unimaginable ways. Stupp and his coworkers designed molecules with the capacity to self-assemble into nanofibers once injected into the body with a syringe. When the nanofibers form they can be immobilized in an area of tissue where it is necessary to activate some biological process, for example saving damaged cells or regenerating needed differentiated cells from stem cells.

This same work also has implications for Parkinson's and Alzheimer's, both diseases in which key brain cells stop working properly.

Canadian researchers 'create' leukemia stem cell, watch disease unfold:

Imagine if scientists could peer into the blood and see the very first aberrant cells that will give birth to leukemia and then watch as the disease slowly progresses and takes over the body.

Well, Canadian researchers have done just that - converted normal human blood cells into leukemia stem cells, then transplanted them into lab mice and witnessed the disease unfold.

...

"What's new and different is they've actually been able to take a specific gene rearrangement that we have known about for quite a number of years in human leukemias and been able to take that specific abnormality and put it back into normal human cells and show that it does in fact cause leukemia."

There should be no doubt that disease and aging - which are, after all, nothing more than undesirable rearrangements of biological molecules - can be defeated in the long run. Look at what can be done today, and extrapolate out by decades of breakneck advances in scale, quality and cost reduction. Moving molecules around with precision and intent is something that scientists are eagerly engaged in perfecting.

The real question of importance is not "if," but rather "when?" Will the technologies of longevity, rejuvenation and healthy life extension arrive soon enough to benefit those of us reading this today? That's very much up to us, and how much we care to help matters along.

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More Melatonin Research
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People - within and without the scientific community - spend far more time than is warranted in the study of compounds and lifestyle that are never going to have a large effect on aging. Yet a ferocious attention is given to the slightest rumor and every study involving food and supplements - while practical methods of moving far beyond the world of pills and diet are neglected. From ScienceDaily: researchers concluded "that the consumption of melatonin - a natural substance produced in small amounts by human beings and present in many types of food - delays the oxidative damage and inflammatory processes typical of the old age. ... not only did this substance neutralize the oxidative stress and the inflammatory process caused by aging, but it also delayed its effects, thus increasing longevity." The further conclusions from the researcher seem overstated - until you realize that melatonin is illegal to use in his country, and dealing with that meddling injustice is partially why this research release exists in the first place. Melatonin may be nothing compared to the prospects of SENS and other future medicine, but people should stand up for the right to ingest whatever they see fit to ingest.

Link: http://www.sciencedaily.com/releases/2007/04/070424062819.htm

Alzheimer's, Gamma-Secretase and Tau
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I should point your attention to another good NYAS presentation summary from recent days: "No consensus emerged on the single best way to tackle Alzheimer's disease. But in a symposium such as this, designed to stimulate discussion and debate, that's probably a good sign: the diversity of opinions and approaches indicates that neurodegenerative disease research is a vibrant and healthy field. Looking toward the near future for new therapies, [gamma-secretase] modulators are probably furthest ahead; some candidates are well into clinical trials. Amyloid immunotherapy - inducing the brain to attack aggregated pathogenic [amyoid-beta] species - is potentially effective, but the first subjects treated with this approach showed serious side effects. Drugs that work upon synaptic transmission also show promise. The wide range of approaches and ideas is encouraging. While the gradual progress of Alzheimer's disease may be painful to watch, its slow time course has a silver lining: the promise of interrupting the disease before it's too late."

Link: http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=5030

Critiquing "The Way We Age"
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Molecular biologist Derya Unutmaz (who maintains Biosingularity, and who was interviewed not so long ago by Attila Chordash of Pimm) made a few comments via the Gerontology Research Group mailing list on the topic of the recent New Yorker piece "The Way We Age":

There are several misconceptions early in the article in my opinion, see my comments below, which are mostly meant for discussion purposes.
These findings notwithstanding, scientists do not believe that our life spans are actually programmed into us.

I am wondering who are these scientists why they do not believe that our life spans are actually programmed in us?

After all, for most of our hundred-thousand-year existence­ - all but the past couple of hundred years ­- the average life span of human beings has been thirty years or less. (Research suggests that subjects of the Roman Empire had an average life expectancy of twenty-eight years.) Today, the average life span in developed countries is almost eighty years. If human life spans depend on our genetics, then medicine has got the upper hand. We are, in a way, freaks living well beyond our appointed time.

This is gross misconception. The reason why the average life span was so low was because most of the deaths occurred during childhood and through infections during adulthood. If one corrects for the infection survival and looks at life expectancy at older age, there has only been about 6-8 years increase in overall life extension in the last 100 years. Thus, the data strongly argues for biological program of aging, and that at current time we are not yet freaks living much beyond our appointed time, just that many more of us reaching the near maximal set program.

So when we study aging what we are trying to understand is not so much a natural process as an unnatural one. Inheritance has surprisingly little influence on longevity. James Vaupel, of the Max Planck Institute for Demographic Research, in Rostock, Germany, notes that only six per cent of how long you'll live....

This is not correct. The most comprehensive Danish twins study found that the genetic factors account for about 25% of longevity, which I think again greatly underestimates the biological genetic program because the life styles vary greatly even between identical twins. If genetically identical twins have the exact life styles, they appear to live remarkably to about the same age, again arguing for biological program.

If our genes explain less than we imagined, the wear-and-tear model may explain more than we knew. Leonid Gavrilov, a researcher at the University of Chicago, argues that human beings fail the way all complex systems fail: randomly and gradually. As engineers have long recognized, many simple devices do not age. They function reliably until a critical component fails, and the whole thing dies instantly. A windup toy works smoothly until a gear rusts or a spring breaks, and then it doesn't work at all. But complex systems­ - power plants, say­ - have to survive and function despite having thousands of critical components.

Again I would argue that wear-and-tear model is gross oversimplification. If the simple wear-and-tear model was true for complex biological organisms then one would not expect wild differences in lifespan of equally complex organisms such a mouse (2 years), human (100 years), Bowhead whales and turtles (200 years), or some plants/trees (1000s of years). This also contradicts with an earlier paragraph in the article.

While the engineering analogies made by some appear intuitive or attractive, they forget the biological systems are autonomous in that they have built in repair and control mechanisms and far more flexibility then material systems. When a gear of a car breaks down or rusts, that car can not repair itself or install a new gear, whereas our bodies perform these operations every day both on the cellular and organismal level. This is a fundamental distinction.

Engineers therefore design these machines with multiple layers of redundancy: with backup systems, and backup systems for the backup systems. The backups may not be as efficient as the first-line components, but they allow the machine to keep going even as damage accumulates. Gavrilov argues that, within the parameters established by our genes, that's exactly how human beings appear to work. We have an extra kidney, an extra lung, an extra gonad, extra teeth.

Mice and humans have exactly the same number of organs and appear to have the same backup systems, why is it that there is a 50 fold difference in their lifespan?

It happens in a bewildering array of ways. Hair grows gray, for instance, simply because we run out of the pigment cells that give hair its color. The natural life cycle of the scalp's pigment cells is just a few years. We rely on stem cells under the surface to migrate in and replace them. Gradually, however, the stem-cell reservoir is used up. By the age of fifty, as a result, half of the average person's hairs have gone gray.

So what if our stem-cell reservoir was never used up? Can we have non-gray and full hairs indefinitely or much much longer? That is to say if the code was written such that stem cells continued renewal for 200 years instead of 50.

Inside skin cells, the mechanisms that clear out waste products slowly break down and the muck coalesces into a clot of gooey yellow-brown pigment known as lipofuscin. These are the age spots we see in skin. When lipofuscin accumulates in sweat glands, the sweat glands cannot function, which helps explain why we become so susceptible to heat stroke and heat exhaustion in old age.

What if the mechanisms that clear out the waste products don't break down or rather stop working? That is if the genetic code was such that garbage collectors continued to do their job.

The eyes go for different reasons. The lens is made of crystallin proteins that are tremendously durable, but they change chemically in ways that diminish their elasticity over time­hence the farsightedness that most people develop beginning in their fourth decade. The process also gradually yellows the lens. Even without cataracts (the whitish clouding of the lens caused by excessive ultraviolet exposure, high cholesterol, diabetes, cigarette smoking, and other unhelpful conditions), the amount of light reaching the retina of a healthy sixty-year-old is one-third that of a twenty-year-old.

This could be one of those conditions that really is due to wear-and-tear, and needs to be regenerated or replaced completely.

I spoke to Felix Silverstone, who for twenty-four years was the senior geriatrician at the Parker Jewish Institute, in New York, and has published more than a hundred studies on aging. There is, he said, "no single, common cellular mechanism to the aging process." Our bodies accumulate lipofuscin and oxygen free-radical damage and random DNA mutations and numerous other microcellular problems. The process is gradual and unrelenting. "We just fall apart," he said.

I would say "it's the genetic program stupid" :)

I think there are gray areas where structure and process as defined by our genes ends and wear and tear picks up; I would present the whole as a case of wear and tear acting on a self-repairing system with certain defined characteristics. The end result is complex, highly varying between individual circumstances, but much more consistent over statistically significant (i.e. large) groupings of similar genes and lifestyles.

One of the fundamental and most important debates amongst those working on the development of longevity medicine is this: do we give priority to changing our program of operation (by, say, manipulating gene expression, altering our genes, or otherwise shifting the activity of proteins in our body), or do we attempt to fix up the wear and tear in the present program of operation. Discussion of the sort Unutmaz engages in above are far from academic: research, development, fundraising and education is taking place today. The foundation of the next decade of research is being laid right now - the effectiveness of that research will mean the difference between life and death for uncounted millions.

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Don't Bet Against Longevity
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(From News.com.au). The world has a way of presenting us with tiny and fleeting replicas of the vast, slow and complex dances that take place behind the scenes of everyday life. Actuarial concerns are engaged in a years-long process of education and change in response to a future of increasing longevity. Billions of dollars are moving with the times - but you'll find that same advance wherever money changes hands over the length of healthy life. "A man who bet £100 ($240) a decade ago that he would live to be 100 is preparing to pick up his £25,000 ($60,000) winnings. So confident was bookmaker William Hill in 1997 that it gladly offered Alec Holden odds of 250/1. ... When we started taking these bets, 100 years old seemed to be an almost mythical landmark and we were prepared to offer massive odds. But these age wagers are starting to cost us a fortune and from now on we are going to push out the age to 110. I am sure that Alec will get more pleasure from our letter than he will from the Queen's."

Link: http://www.news.com.au/story/0,23599,21610403-1702,00.html

Organ Printing in a Nutshell
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RSC Publishing provides a compact overview of the application of bioprinting technologies: "In order to build an organ, you need four components: cells (the bio-ink), a biomaterial (the biopaper), a device to make three-dimensional structures (the bioprinter), and a method to aid tissue assembly and maturation (the bioreactor). In addition to this shopping list, you need the expertise to put the components together, and you need funding. Enter the hydrogel chemists, the cell and developmental biologists, the physicists, the computational modellers, and a company that builds rapid prototyping devices. ... in many ways, the biomaterial is the easy part. Shaping an artificial 'neo-organ', developing the printing tools and a computer model for layer-by-layer construction, and devising a strategy to mature the neo-organ before transplantation are among the main challenges." If you can build organs from a patient's cells - or even meaningful amounts of undamaged tissue for transplant - that will make an enormous difference to the future of health and longevity.

Link: http://www.rsc.org/Publishing/Journals/cb/Volume/2007/5/organ_printing.asp

An Interview With Robert Freitas
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I seem to have failed to notice a recent interview with nanotechnologist and healthy life extension advocate Robert Freitas, conducted by Michael Anissimov. The discussion is mostly concerned with matters of interest to the Lifeboat Foundation, but the interview opens with this new news:

My professional goal for the last two decades has been, and continues to be, to help make life-extending medical nanorobotics technologies happen as fast as humanly possible. ... I've been trying to figure out how to build diamondoid nanorobots, starting from current manufacturing technologies.

...

culminating 5 years of intermittent effort I've finally finished my latest theoretical scaling study of a new diamondoid medical nanorobot called the "chromallocyte". This is the first full technical description of a cell repair nanorobot ever published. The nanorobot design addressed in the paper is a very important one - it is perhaps the key nanorobotic system for anti-aging and life extension applications.

Quoting part of the abstract:

"The ultimate goal of nanomedicine is to perform nanorobotic therapeutic procedures on specified individual cells comprising the human body. This paper reports the first theoretical scaling analysis and mission design for a cell repair nanorobot. One conceptually simple form of basic cell repair is chromosome replacement therapy (CRT), in which the entire chromatin content of the nucleus in a living cell is extracted and promptly replaced with a new set of prefabricated chromosomes which have been artificially manufactured as defect-free copies of the originals. The chromallocyte is a hypothetical mobile cell-repair nanorobot capable of limited vascular surface travel into the capillary bed of the targeted tissue or organ, followed by extravasation, histonatation, cytopenetration, and complete chromatin replacement in the nucleus of one target cell, and ending with a return to the bloodstream and subsequent extraction of the device from the body, completing the CRT mission...."

The title of the paper is "The Ideal Gene Delivery Vector: Chromallocytes, Cell Repair Nanorobots for Chromosome Replacement Therapy" and it is currently in press at the peer-reviewed Journal of Evolution and Technology (and is soon to be available online).

If you want a good look at the medical engineering of 2040 - at the technologies that will be in full swing at the same time as we have refined regenerative medicine to an expert art and know all there is to know about our own biochemistry - then pay attention to the work of Robert Freitas. There's more to repair in and around an aging cell than just damaged DNA, but if the medical community of the time can build and control millions of chromallocytes, I'm willing to grant that the rest of the job is well within reach via similar methods.

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The Way We Age
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The New Yorker looks at medicine and aging; folk on the Gerontology Research Group list have been disputing some of the presented information, but it's a decent article overall: "Nonetheless, as the defects in a complex system increase, the time comes when just one more defect is enough to impair the whole, resulting in the condition known as frailty. It happens to power plants, cars, and large organizations. And it happens to us: eventually, one too many joints are damaged, one too many arteries calcify. There are no more backups. We wear down until we can't wear down anymore. ... Hair grows gray, for instance, simply because we run out of the pigment cells that give hair its color. ... We rely on stem cells under the surface to migrate in and replace them. Gradually, however, the stem-cell reservoir is used up. ... Inside skin cells, the mechanisms that clear out waste products slowly break down and the muck coalesces into a clot of gooey yellow-brown pigment known as lipofuscin. ... The eyes go for different reasons. ... Even without cataracts [the] amount of light reaching the retina of a healthy sixty-year-old is one-third that of a twenty-year-old. ... There is [no] single, common cellular mechanism to the aging process. Our bodies accumulate lipofuscin and oxygen free-radical damage and random DNA mutations and numerous other microcellular problems. The process is gradual and unrelenting. ... We just fall apart."

Link: http://www.newyorker.com/reporting/2007/04/30/070430fa_fact_gawande?printable=true

All the More Reason For AGE Breakers
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A research team recently demonstrated that a diet lower in advanced glycation endproducts (AGEs) extended life in mice: "Aging is accompanied by increased oxidative stress (OS) and accumulation of [AGEs]. AGE formation in food is temperature-regulated, and ingestion of nutrients prepared with excess heat promotes AGE formation, OS, and cardiovascular disease in mice. We hypothesized that sustained exposure to the high levels of pro-oxidant AGEs in normal diets (RegAGE) contributes to aging via an increased AGE load [and a same-calorie] AGE-restricted (by 50%) diet (LowAGE) would decrease these abnormalities. ... This was associated with a reduction in systemic AGE accumulation and amelioration of insulin resistance, albuminuria, and glomerulosclerosis. Moreover, lifespan was extended in LowAGE mice, compared with RegAGE mice. Thus, OS-dependent metabolic and end organ dysfunction of aging may result from life-long exposure to high levels of glycoxidants ... A reduced AGE diet preserved these innate defenses, resulting in decreased tissue damage and a longer lifespan in mice." More attention should be given to developing AGE breaker drugs. Diet is just one source - your body also creates AGEs itself as a byproduct of metabolic processes.

Link: http://www.ncbi.nlm.nih.gov/pubmed/17446314

What Happens When Science Is Not Your Guide
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Following feelings - or even experience - rather than the findings of the scientific community is not the best path forward under most circumstances. A piece on calorie restriction and anorexia by a recovered anorexic at Slate is very illustrative of this point:

As a former anorexic, I've found it strange to hear scientists hail low metabolism - a central feature of that disease - as a sign of health and potential longevity. When I was being treated, my doctors invoked my low metabolism as a catchall for the physical damage I was doing. My low heart rate, amenorrhea (the loss of my period), and the goose bumps I got in 70-degree weather were all signs of illness. So, how can something that is a symptom of disease in one person be a marker of good health in another?

...

The same thing happens in people who practice CR seriously. Your body doesn't know whether you're eating only two-thirds of a normal caloric intake in order to lose weight, or to live forever, or because the crops have failed or the antelope died out. And I'd argue that a lot of CRONies are susceptible to the addictive nature of starvation, because they begin CR out of a sense of dissatisfaction with their lives.

How do I know? Because to write about this, I joined the Calorie Restriction Society, browsed the archives of their e-mail list, and interviewed several CRONies. Tomorrow, I'll explain how my interviews led me to conclude that calorie restriction, while not anorexia, constitutes its own new kind of eating disorder.

While I have a certain sympathy towards anorexics - or indeed anyone who suffers though self-destruction - I can't help but feel that the anorexic who describes CR as an eating disorder is much the same as the cutter who views all surgery as nothing more than self-multilation. The lens is firmly in place, coloring the whole world one particular shade of purple.

The article is a good example of a particular type of nonsense propagated about the practice of calorie restriction. CR practitioners are, in general, level-headed folk who have much the same attitude towards diet as good atheletes: optimize, optimize, optimize. Follow the science - you'd have to be someone who cares nothing for your health and longevity to dismiss CR without a second thought.

A good antidote to this sort of hit piece is to get out there and read around the CR blogging community. They're all regular folk who like to be healthy, and have found a very effective means to achieve that end. As April Smith puts it:

No one is trying to get other people to do CR. Can those of you who out there who are on a crusade to stop other people from eating a healthy diet please just leave us in peace? We've done nothing to hurt you, and us giving up our healthy lifestyle won't help you. Unless of course it makes you feel better about your own problems. We're fine. We're healthy, happy people... except when we're being attacked in national magazines.

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NYAS On Cancer Stem Cells
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It's all cancer all the time this week: the cancer research community is large, and the annual meetings generate a great deal of coverage from the popular science press. Here, the NYAS gives another of their excellent overviews: "Although the groundswell of interest in cancer stem cells is new, the concept has been around for more than 40 years. [It] languished until the mid-1990s, when researchers finally obtained the tools and knowledge to explore the hypothesis. ... Researchers believe that cancer stem cells are either stem cells that have mutated to undergo uncontrolled cell division and differentiation, or are already-differentiated tumor cells that through mutations have regained the ability to self-renew. ... If a normal stem cell acquires mutations, or one of its progenitor cells acquire mutations, this could form a cancer stem cell ... Still under discussion is how similar cancer stem cells are to normal stem cells. ... The 'stem cell' term implies that the cell is like normal stem cell but that may or may not be more accurate. 'Tumor-initiating cells' might be a more accurate definition. ... The opportunity for finding new targets and new mechanisms to attack cancer is extremely exciting. I think we have a lot of challenges ahead."

Link: http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=5055

Aubrey de Grey at the Global Investors Forum
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The Methuselah Foundation chair Aubrey de Grey recently presented at the UBS Global Investors Forum: "The event was attended by somewhat more than 100 quite senior people from pension fund management, life assurance and wholesalers of long duration investments to institutional clients. Aubrey de Grey was one of three speakers to open the event, addressing the whole audience. His warm-up man was Joseph Stiglitz (Nobel Prize Economics 2001) and he was followed by Sir Christopher Hum (formerly HM Ambassador to PRC). ... the audience did not seem to find the ideas expounded ludicrous. There were some titters at the "1000 year lifespan" slide. I asked people around me afterwards what they thought, and nobody denied the plausibility/desirability of the notion. My neighbour unprompted told me that the rich would find the prospect of more life irresistible. Questions from the floor concerned timescale and current indications of progress. ... the industries most exposed to financial risk and gain as a result of rapid changes in life span are further ahead than the man in the street in appreciating the possibilities ... those with a large stake in the future will take the time to evaluate the prospects for longer lives, and go on to educate others. This meeting was a leading indicator, showing that the idea of dramatic longevity gains is beginning to enter the mainstream."

Link: http://blog.methuselahfoundation.org/2007/04/methuselah_foundation_at_the_g.html

Glancing at the Foreign English Language Press
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The English language sections of oveseas newspapers and online news sites are ever an interesting mirror, for all the obvious reasons. It is often something akin to seeing the final product of a chain of poorly communicated instructions - several translations, a quite different approach to journalism, and people with little knowledge of the subject matter may be involved in the process. Or more so than is usual for local media, in any case - who are bad enough in their own way.

I've been keeping a weather eye on the appearance of topics relating to healthy life extension in the foreign press over the past few years: the slow migration of the overseas English language press towards a more accurate reflection of healthy life extension news is one measure of progress in advocacy and awareness.

Here are a couple of examples from the past few days; for all the errors, the quality of the content is somewhat improved over the median of past years.

Freeze, i’m not dead:

"Yes, it’s only a small chance but it’s a huge gamble,” said the institute’s media manager Chrissie de Rivaz (www.cryonics.org).

And surprise, surprise! It has emerged that a Malaysian is among its 70-odd members, with the rest being Britons.

In all probability, the person could be the only Malaysian who has placed enormous faith in cryonics (the word derives from cryogenics, meaning the physics of extreme cold).

Like the other members, they were convinced that if they were frozen carefully and quickly soon after their deaths, their bodies could be maintained indefinitely until science found a cure for whatever illnesses that claimed their lives.

When that time comes, they hoped future generations would be able to take them out of cryogenic suspension, thaw them out, jump-start their brains, restore their memories and repair the damage the Cryonics team inflicted as they prepared their bodies to be frozen.

Eternity code: Never say die?

Immortality is the stuff of legends, but researchers are already working towards the next best thing: living to a ripe old age without having to grow old. Eventually, they say, there would come a time when ageing would become dispensable.

"Ageing is simply a side-effect of being alive. It would soon be possible to control the biological processes that lead to it," claims Dr Aubrey de Grey, who's been researching the human ageing process at Cambridge University.

...

This, however, doesn't mean we can eliminate ageing from our biological system altogether. Rather, there will be treatments that repair molecular and cellular damage periodically, say, after every decade or so it would be just like maintaining an old house or a vintage car, says de Grey.

In effect, it will be somewhat like always being one step ahead of death. "Average life spans in this scenario could be 1,000 years and more," says de Grey.

...

Will all this be the harbinger of eternal youth? "Indefinite youth, rather than infinite youth," corrects de Grey, "since, at this stage, our susceptibility to disease and other causes of mortality would be that of a young adult much lower than that of an elderly adult, but not zero."

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What Would You Do With 20 Extra Years?
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Let us examine this hypothetical: as an adult of middle or later life, you suddenly find you have twenty extra years of health and no further aging, inserted into your life starting right now, this instant. How does this change your plans? How does this change the pressures you feel?

Twenty years is a very long time. Look back at the person you were twenty years ago, what you knew, how skilled you were, where your focus was - a great deal of change since then, no? It's time enough for two professions, an accomplished mastery, a brace of novels, or five or six attempts to build a winning startup company. Time enough to build and change a dozen rewarding social circles, or save enough money to retire in modest leisure for a couple of decades.

Are there good reasons why you haven't take a few years off to be a low-cost traveler around the world? To learn blacksmithing because you think it's interesting? To work for a non-profit and give your time to an important cause? If you have additional decades given to you, would those reasons change?

These hypotheticals are not quite so hypothetical, of course. They are all worth thinking about, because one day, sometime prior to 2020, those us who grew under the learned expectation of threescore-and-ten-and-then-you're-old-and-done - dripping from every education in the classics, or daily saturation in popular culture for that matter - will suddenly realize that the real world has actually become something more like fourscore-and-ten, with that limit increasing at a fair clip.

The systems biologists seem fairly confident that the scientific community will manage that gain just through becoming generally better across the board in medicine - without even trying too hard to tackle aging as a chronic medical condition with specific causes that can be addressed. The actuaries, whose billion-dollar clients falter or thrive by the slightest change in mortality rates or longevity, see longer lives ahead. The leading signs are there - and that isn't to even mention the growing community of researchers directly engaged in scientific work to halt and reverse aging.

So: 20 extra years. Think about it. What is that worth to you? Worth enough to help make it happen?

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The Trend
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Eric Mahleb illustrates the trend to a future of great and increasing longevity by way of reviewing Rapture: "For many years, scientists have tried to disassociate themselves from what has been perceived by many as the extravagant rants of a few delusional individuals whose only purpose is to become immortal ubermensch. Yet, in the past 15-20 years, words such as cloning, gene therapy, designer babies, artificial intelligence, stem cells, and nanotechnology have taken their place in the everyday language of millions of people. And many scientists are no longer afraid to state that they are working on ways to stop disease, aging, death, and on how to improve human performance and appearance. Whether you are against them or for them, these technologies are slowly becoming part of our lives. ... There is a counter movement, naturally, that tries to warn humanity of the perils of such a direction. ... For them, disease, sadness, death, all are part of our human nature. Try telling this to someone whose son or daughter are in a wheelchair or were born with an incurable disease that will prevent them from living past the age 30. The future can be scary, but the future is inevitable. Part of our 'nature' is to continuously move towards it, good or bad. I am prepared." People want health and life; if we can but illustrate how close we are to technologies of rejuvenation, support and resources directed towards research will increase greatly.

Link: http://www.yume.co.uk/rapture-a-raucous-tour-of-cloning-transhumanism-and-the-new-era-of-immortality

WebMD On Cancer Stem Cells
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WebMD gives an overview of some of the latest research into cancer stem cells: "Are most current cancer treatments -- as well as many in development -- aimed at eradicating the wrong cancer cells? That's the position of some leading researchers, who say that cancer is, fundamentally, a stem cell problem -- and that therapy should be targeted at so-called cancer stem cells. ... In the stem cell hypothesis, cancer is driven by specific cells that contain stem cell properties ... These cells then reproduce and replenish malignant tumors. Currently, most treatments target cancer cells, but not necessarily cancer stem cells ... While the treatment may shrink the tumor and keep it in check for a while, eventually, the untreated cancer stem cells proliferate into cancer cells, leading to a return of the tumor and death ... If the treatments targeted the cancer stem cells, however, the tumor would lose the ability to generate new cancer cells, eventually resulting in a cure." The article goes on to look at some specific demonstrations of errant stem cells and stem-like cells from recent months.

Link: http://www.webmd.com/cancer/news/20070420/stem-cells-may-be-at-root-of-cancer?print=true

Cancer Gene Therapies Becoming Very Impressive
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(From EurekAlert!). It seems as though we will have the chance to see whether widespread access to efficient therapies for cancer is good enough to ensure the healthy life extension brought about by other advances in medicine. The work presently taking place in the lab is fairly impressive: researchers "designed a novel viral-based gene therapy they say blasts through a body, targeting both primary and distant tumors, while leaving normal cells untouched. In the 15 mice they tested, injections of the therapy in tumors on one side of the mouse eliminated those cancers as well as tumors on the other side of the animal's body, producing a cure in all of the mice. This study tested this 'dual cancer-specific targeting strategy' with aggressive therapy resistant prostate cancer. The researchers have also shown it works in animals with breast, and melanoma tumors. ... The beauty of this approach is that two methods are being used to destroy a tumor. The virus we designed replicates within a tumor, and at the same time produces a massive amount of a cancer killing compound. Either action alone is damaging and potentially deadly, but together they are lethal."

Link: http://www.eurekalert.org/pub_releases/2007-04/aafc-gtc041007.php

The High Level View of Curing Cancer
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This ScienceDaily piece illustrates well that to eradicate cancer utterly will require radical change to our biochemistry. "Cancer is a fundamental consequence of the way we are made. We are temporary colonies made by our genes to propagate themselves to the next generation. The ultimate solution to cancer is that we would have to start reproducing ourselves in a different way. ... Although DNA repair is favourable to the organism; it may not be favourable to the individual cell. ... Deciding when to stop for repairs and when to keep on going is a difficult challenge. Making repairs assures an optimized vehicle, but it also consumes valuable time and resources. At first thought, it may seem obvious that a damaging environment calls for more repair. Paradoxically, however, the effect may be exactly the opposite. Imagine that you are racing through a war zone with constant bombardment. Stopping for repair can then be a fatal strategy, and it is better to keep on going with flat tires and a screaming engine than to stop for repairs ... Cells exposed to particular carcinogens die if they have the relevant repair mechanism, while genetically unstable cancer cells continued to grow." But we can get a long way on the next generation of prevention and therapies - hopefully far enough to see much more advanced technologies needed to remove cancer from the human condition.

Link: http://www.sciencedaily.com/releases/2007/04/070416160429.htm

Tip For the Day
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If you're thinking about starting up an informational website or business focusing on the usual items of interest relating to the "anti-aging" marketplace - you know the drill: supplements, alternative medicine, and so on - and approach me out of the blue asking to use content from Fight Aging! and the Longevity Meme in your endeavor, don't expect to be showered with support. I am no friend of the mainstream "anti-aging" marketplace and deplore the damage it does to actual, serious efforts to extend healthy life span.

This is true even if you happen to be a supporter of the Mprize, a long-time reader, and so on and so forth. It's never pleasant to have to turn down polite, earnest, overreaching requests, but I will - so it's easier all round if you just don't ask.

The terms under which anyone can make use of what I write here at Fight Aging! - without asking, even - are in the sidebar. It's all under the Attribution-NonCommercial-NoDerivs Creative Commons license; do as you will provided you keep the work intact, attribute the author and don't make money from it.

As for the Longevity Meme, a range of the material there is syndicated in ways that should make it easy to incorporate into your website. Again, no need to ask, it's sitting right there and available under the non-onerous terms of the syndication agreement.

If I want to do more than this for specific cases, I will. But I can guarantee that won't happen for someone I'm talking to for the first time today.

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Cheaper Antibodies, Faster Medical Progress
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Continuing the infrastructural theme for today, ScienceDaily reports on better ways to produce antibodies for new therapies: "The group [developed] the new antibody-production approach to improve upon processes used previously to identify new drugs. Drug companies have used those more time- and labor-intensive processes to develop antibodies for treating rheumatoid arthritis, cancer and other diseases. The new approach [overcomes] those obstacles, and has other advantages. ... Our approach can provide a significant time savings. and it enables antibodies to be isolated to treat human diseases that may not be possible to obtain otherwise. ... Getting mammalian cells to produce lots of antibodies costs more, and can take several months. The direct bacterial approach [shaves] weeks off the production process." Real progress lies in making your tools and products work better and cost less in time and resources. That's what leads to more research, more widespread usage, and thus a greater rate of experimentation and improvement.

Link: http://www.sciencedaily.com/releases/2007/04/070418104254.htm

Stem Cell Infrastructure Improving Rapidly
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(From innovations report). A good place to watch for meaningful trends in science and engineering is infrastructural work - rarely flashy, but always a better measure of progress. In the stem cell field, progress is continuing apace: researchers "developed an economical tissue engineering approach which could offer new possibilities for restoring damaged or lost knee cartilage tissue. ... 'Routine tissue culturing methodologies cannot cope with the scale of cell production required to create world stem cell banks for engineering knee cartilage tissue,' explains Professor Al-Rubeai. His research group has optimised the tissue culture techniques so they can grow more stem cells in vitro which have the characteristics or morphology of in vivo stem cells. This is the first study to factor in economics. A key objective of our work is to develop a model for the biopharmaceutical industry by generating a cell bank using an affordable technique. A 17-fold expansion factor was consistently achieved and large numbers of stem cells for tissue culture engineering were obtained." Cheaper tools mean more experimentation, which leads to more rapid results - which leads to cheaper tools. It's a virtuous cycle that will accelerate progress in medicine capable of tackling aspects of age-related degeneration.

Link: http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-82981.html

The Wrong Direction
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A great deal of novel, exciting scientific research is harnessed towards very inefficient ways of dealing with age-related degeneration and disease. The path of inefficiency is the path of patching without addressing root causes, of papering over the rot and hoping for the best. This sort of application is destined for failure - by which I mean it will succeed in obtaining small benefit at great cost, and in the process tie up resources, support and expectations that might have gone to more efficient ends.

Two examples:

UCLA/Toronto researchers unlock key to memory storage in brain:

"We discovered that the amount of CREB influences whether or not the brain stores a memory," said Silva. "If a cell is low in CREB, it is less likely to keep a memory. If the cell is high in CREB, it is more likely to store the memory."

Human implications of the new research could prove profound.

"By artificially manipulating CREB levels among groups of cells, we can determine where the brain stores its memories," he explained. "This approach could potentially be used to preserve memory in people suffering from Alzheimer's or other brain injury. We may be able to guide memories into healthy cells and away from sick cells in dying regions of the brain."

Returning the Springiness to Arthritic Joints:

Arthritis is a joint disorder that affects nearly 40 million people in the United States. It's often the result of an activity-related injury that damages some part of the joint, and it's characterized by inflammation, which is painful and makes the joints stiff and swollen.

Currently, there is no preventative method for arthritis; there are only treatments to reduce joint pain and inflammation. In one particular treatment, a gooey polymer made of hyaluronate - long thought to be the substance that gives joint fluid its resiliency - is injected into the joint.

People will do as they will, of course, but we should not be looking to this sort of work as the way to the future. When there are only so many billions of dollars to be had for medical research, a focus on patching and inefficient methodologies will mean we are doomed to see only lesser results - we must be smarter than that, now that modern technology allows us to do better. The focus should be on root causes, damage and repair, because the cost of developing far better solutions based upon that approach is not much different from the patching, on balance.

Why be slow when we could be faster?

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Alzheimer's Drugs Looking More Promising
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Better biotechnology means a better approach to new drugs: start with an understanding of the biochemical mechanisms of age-related disease, and find a compound that can safely interfere in those mechanisms. From ScienceDaily: "Tang discovered a key enzyme called memapsin 2, or beta-secretase, that is involved in the development of Alzheimer's disease. The action of this enzyme on a special protein, called the amyloid precursor protein, leads to the formation of plaques in the brain. The development of an inhibitor compound targeting memapsin 2 could block this reaction, thus preventing the disease. Utilizing Tang's information about the enzyme, Ghosh designed the first memapsin 2 inhibitor. ... This is the most exciting target today for Alzheimer's disease intervention. These interactions happen at a very early stage in the disease, and if we could block them, we could prevent many of the harmful steps that follow and drastically reduce the impact. In our most recent tests, a single dose of the designed compound reduced the beta-amyloid level by 30 percent."

Link: http://www.sciencedaily.com/releases/2007/04/070417160548.htm

Investing in Immortality
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A pitch for one facet of shaping the context of the rest of your life - for what else is investment? - via Accelerating Future: "Few would rush to accept an offer of immortality if each successive year were to bring an ever-increasing burden of broken hips, memory loss, and incontinence. This may help explain why so many people find the thought of extreme life extension unpalatable; the best years are not usually represented by triple digits. Hence, those who actually intend to live forever usually know something about the technology that would make this possible. They understand how the same research that could ultimately conquer aging will also be critical to treating the ailments associated with it. This conclusion is not a difficult one; even today, the leading causes of death for people in their physical prime are not diseases, but accidents, homicide, and suicide. If the biological clock could be stopped or reversed, careful individuals could live in excellent health for a very long time. ... No single portfolio can ever right for everyone. But if you are interested in the possibility of living indefinitely - if the thought of going 'gentle into that good night' angers you - there are investments you can make."

Link: http://www.acceleratingfuture.com/michael/blog/?p=402

If You Support Radical Life Extension, Be Open About It
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In the course of commenting on his appearance in Psychology Today article - ostensibly about people who tilt at windmills, but inadvertently a good commentary on how human nature tends to categorize any ambitious project as impossible - Michael Anissimov makes this observation:

The middle of the article engages in slightly tautological reasoning when it says that the immortalist movement’s image is damaged by Ray [Kurzweil] and Aubrey [de Grey] because they do things in pursuit of immortality, like taking supplements or marketing life extension research. They are doing things characteristic of immortalists. If they didn’t do them, they wouldn’t be pursuing immortality. Thus the author is essentially saying “immortalists are damaging the immortalist movement by acting like immortalists”. It’s a roundabout way of saying, “I’m pretty uncomfortable with the whole thing but don’t want to say so outright in this article”.

"Immortality" here being, I think, "physical immortality" or agelessness. The defeat of degenerative aging via future technologies of repair and rejuvenation, in other words - technologies that won't up and build themselves. We'll have to make that happen, but it's just a matter of time and resources.

There is a strong pressure, both internal and external, to conform to the median view in any human society; we're still very much rickety devices built upon a pillar of apes in that way. But you don't enact change by hiding your real views under a bushel. Equally, you can't take the average knee-jerk objection to healthy life extension seriously - give the objector 20 years or so, and they'll be conforming to the new median view you helped bring about.

If you want to change the world for the better, read around the subject of healthy life extension via scientific progress. Make your own mind up, and plant the flag exactly where you think it should be. The farther out the better, given just how far behind popular culture is these days. Then help make it happen, and convince as many people as you can along the way. That's how progress is made - not by bowing down to the unseen pressure and agreeing that the plausible is instead impossible.

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The Future of Regenerative Medicine
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The promising future of regenerative medicine is evident in the work taking place now - both so obviously crude and so obviously far ahead of what has been possible in the past. Genetic Engineering News illustrates: "The idea of growing an organ from one's own cells or healing spinal cord injuries with cells transformed from embryonic stem cells used to be considered fodder for science fiction movies, but no more. Companies are not only developing technologies that can do exactly that, but these methods provide real potential to cure certain conditions and diseases. ... We have published a paper showing, for the first time, that we can create RPE (retinal pigment epithelium) from human embryonic stem cells ... RPE is the layer of cells that maintains the photoreceptors, cones, and rods and enables vision. ... We're hoping to transplant these cells to attenuate vision loss or prevent further progress of macular degeneration ... the same RPE can significantly attenuate visual loss in animal models due to RPE loss. We were able to significantly rescue the photo receptors and saw about 100% improvement in visual acuity in the animals transplanted with these cells."

Link: http://www.genengnews.com/articles/chitem.aspx?aid=2081

More Edmonton Aging Symposium Video
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Much more video from the Edmonton Aging Symposium is available for download: presentations on calorie restriction science; searching for the mechanisms of regeneration in lower animals; AGEs and AGE-breakers; the latest results from studies of MRL mice; progress in LysoSENS; mitochondrial DNA mutations and their role in aging; immunotherapies directed against age-related conditions such as Alzheimer's; how and why the aging immune system becomes ineffective; healing damaged hearts with stem cells; and much more. "The University of Alberta Audio/Visual support, Koi Media and especially Capital Health provided absolutely amazing service and professionalism in putting this together. I cannot thank them enough for the hardwork and dedication when the going got rough. They made the chaos appear a lot less so. I hope you enjoy this chance to review some of the presentations you may want to see again or watch the ones you may have missed." The content is hosted on Methuselah Foundation hardware, so please do your part to help take the load off the servers by posting these videos to Google Video, YouTube, or other video sharing sites.

Link: http://www.edmontonagingsymposium.com/index.php?pagename=eas_archive

A Sample of Modern Cancer Research
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A fair amount of the most interesting and inventive modern biotechnology work is taking place in the cancer research community - and the technology platforms demonstrated this year will come to be used for many other purposes in medical science in the years ahead. All this activity and progress is a very good thing, because cancer is as fundamental for mammals as rust is for iron; absolute victory over cancer will require the development of greater capabilities in biomedical science. The faster the better so far as that is concerned.

With the annual meeting of the American Association for Cancer Research underway, more examples of ingenious research are finding their way into the popular science press.

Cancer vaccines - Taking a jab at cancer by stimulating the immune system:

Researchers from the University of Pittsburgh and the Gunma University School of Medicine have developed a vaccine that enlists multiple parts of the immune system into targeting p53 in head and neck squamous cell cancer. A phase I clinical trial of the vaccine is currently underway at the University of Pittsburgh Cancer Institute.

According to researchers, this is the first vaccine that takes a multi-pronged approach to stimulating the immune system with derivatives of wild type - or non-altered - p53, a tumor suppressor gene. Loss of suppressor function or alteration of the p53 gene factors into nearly 80 percent of human tumors. Tumor cells with altered p53 generally tend to accumulate the protein, which led the researchers to create a strategy that would allow the immune system to destroy tumor cells by targeting p53.

"Instead of creating a vaccine based on mutant p53, which would require a custom vaccine for every patient, our strategy is to target parts of the unaltered p53 protein that can best activate the immune system," said Theresa Whiteside, Ph.D., professor at the University of Pittsburgh School of Medicine. "We are using different unaltered portions of the p53 molecule to entice the immune system into attacking tumors."

Pancreatic cancer vaccine halts progression of disease in some patients:

"Pancreatic cancer is extremely resistant to chemotherapy and radiation and, as a result, has a very high mortality rate," said Andrew Lepisto, Ph.D., first author of the study and post-doctoral researcher, department of immunology, University of Pittsburgh School of Medicine. "One strategy to improve the odds of survival is to help the immune system recognize the presence of pancreatic cancer cells and attack them. Our study, although small, demonstrates that this strategy can be used with some success in pancreatic cancer patients by slowing down, or even stopping, the progression of cancer."

Gene therapy, cancer-killing viruses and new drugs highlight novel approaches to cancer treatment:

Researchers in Germany have hidden vaccine-grade measles virus inside artificially generated blood cells in order to devise a search-and-destroy therapy for human brain cancer that can’t be "seen" by the immune system.

They say their mouse experiments show a proof of principle that this non-pathogenic virus can attack glioma by getting inside tumor cells and replicating, destroying the common brain tumors from the inside out.

This last one is particularly illustrative of mix-and-match cleverness in biotechnology - you should follow the link and read the whole description. Scientists are uncovering all sorts of tools, and those with an engineering bent are assembling new machinery to accomplish tasks never before attempted. We should all be very concerned about cancer and our future - more clearly, we should be very concerned with keeping this sort of progress in medical science moving ever faster towards prevention and cure for the cancers that wait for us in the years to come.

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Follow the Money To Find the First Therapies
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ABCNews reminds us that you'll find the first (expensive, comparatively crude) experimental application of new technologies right where the money is. In the case of tissue engineering and regenerative medicine, modern athletics is one such location: "some researchers are optimistic that sports medicine could reap the benefits of stem cells in the foreseeable future. ... In athletes, we will probably first see stem cells being used to treat meniscus injuries in the knee and tendon injuries ... We could also see it used in ligament reconstruction in the knee. ACL repair is a common operation -- typically you take part of a ligament from a donor site in the knee. Instead we might be able to use a patient's own cells to grow their own ligament. ... one company is currently in the early phases of a clinical trial for a new technique to repair the meniscus -- a crucial wedge of cartilage in the knee joint. ... Although the trial is still in its early stages, he said these therapies may one day allow athletes to heal more completely and faster than ever before. ... Stem cell therapy is much closer than people think. Once that happens, it's really going to open up the door for large-scale stem cell therapies to invade into other areas and become part of the armament of sports medicine physicians."

Link: http://abcnews.go.com/Health/print?id=3038931

Deciphering the Cause of ALS
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SFGate looks at one of the promising uses of stem cells in practice: as testbeds to uncover biochemical mechanisms in neurodegenerative disorders. "Researchers reported evidence Sunday as to what may be causing ALS, or amyotrophic lateral sclerosis, which is marked by the loss of specialized nerve cells, known as motor neurons, that drive conscious movement. The studies implicate a toxic factor in the cellular environment surrounding the motor neurons, rather than something in the neurons themselves. That means any transplanted nerve cells - even healthy motor neurons produced in pristine laboratory conditions from colonies of human embryonic stem cells - would probably die, too, if implanted in an ALS patient. But that doesn't mean stem cells are useless in treating ALS - in fact, they were used in the very laboratory experiments that produced the latest findings. ... Further research is under way to identify the toxin, and perhaps find out how the astrocytes go awry, possibly through some combination of genes and environmental exposure. Eventually, researchers may be able to concoct a drug to neutralize the poisonous effect or use some other strategy to make nerve cells resistant."

Link: http://sfgate.com/cgi-bin/article.cgi?file=/c/a/2007/04/16/MNGB9P9C5N1.DTL

We Must Learn To Better Guard the Brain
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We are our brains - all that we are, and that life means for us is contained within. Perhaps the most vital of all lines of technological development are those devoted to protecting and repairing the brain. It seems very plausible that medical science could be capable of growing any organ - on demand, from your own tissue, and possibly with the accumulated biochemical damage of the years erased - some 30 years from now. Your body might be as new as you'd like it to be ... but the brain is in a class of its own. You can't simply up and replace the brain, so we'd better become very good at repairing and protecting it.

A glance at the work taking place today in laboratories around the world indicates just how far we have to go to reach the end of this path:

Brain Tumor Vaccine Trial Shows Promising Results:

A vaccine for treating a recurrent cancer of the central nervous system that occurs primarily in the brain has shown promise in preliminary data from a clinical trial at the University of California, San Francisco.

...

"Our goal is to change the management of recurrent glioma from a life threatening disease, in which survival rates are typically 25 to 26 weeks, into a chronic disease with extended survival and improved quality of life for patients," Parsa said. "Although our survival data are encouraging, a larger phase 2 study will be required to determine the benefit of vitespen for patients with recurrent glioma. The consistent, tumor specific immune response seen in these patients suggests that in the right patient population, the vaccine could have a significant impact."

Brain structure changes years before memory loss begins:

Researchers performed brain scans and cognitive tests on 136 people over the age of 65 who were considered cognitively normal at the beginning of the five-year study. Participants were then followed annually with neurologic examination and extensive mental status testing. By the end of the study, 23 people had developed [mild cognitive impairment (MCI)], and nine of the 23 went on to be diagnosed with Alzheimer's disease. The brain scans of the 23 people with memory loss were then compared to the 113 people who remained cognitively normal.

Compared to the group that didn't develop memory problems, the 23 people who developed MCI or Alzheimer's disease had less gray matter in key memory processing areas of their brains even at the beginning of the study when they were cognitively normal.

"We found that changes in brain structure are present in clinically normal people an average of four years before MCI diagnosis," said study author Charles D. Smith, MD, with the University of Kentucky Medical Center in Lexington and member of the American Academy of Neurology. "We knew that people with MCI or Alzheimer's disease had less brain volume, but before now we didn't know if these brain structure changes existed, and to what degree, before memory loss begins."

These are the days of exploration and very incremental success, the early days of the biotechnology revolution. Researcher work with tools and knowledge that would have been - and in some cases were - science fiction in past decades. At the same time, we are but stumbling about in the dark with a shovel in comparison to what we know is possible for the decades to come. Yet the tools will become ever better, and progress builds upon progress. We have seen the growth in computer hardware, software and the internet over the past decades - this sort of growth is possible in biotechnology and medicine too, if regulators step aside to allow it.

If we want to live a long, long time in good health, ten thousands incremental advances of the sort quoted above will be but a part of the progress required. It might look like a steep cliff to climb, but it will happen. Our task is to ensure it happens fast enough to benefit us, rather than those who come after us.

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On Biomarkers of Aging
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InfoAging interviews Richard Sprott of the Ellison Medical Foundation in connection with a conference on biomarkers of aging later this year: "The National Institute on Aging began its Biomarkers of Aging project in 1987. I headed up the program, which was looking to identify biomarkers of aging in mice with the ultimate goal of developing a panel of biomarkers that would be useful for humans. Over the course of 10 years, we invested thousands of research hours and millions of federal dollars, only to end up with some interesting possibilities but no clear winners. ... using new tools that weren't available 10 years ago, [there's] a feeling among a number of us that the time is right to have a new effort and that there's the real possibility that we can achieve what wasn't possible 10 or 15 years ago. ... a so-called 'anti-aging' medicine industry has promulgated the notion for a very long time that there are lots of biomarkers of aging out there when they're trying to sell certain kinds of products to the general public. Those biomarkers, in fact, don't exist. The biomarkers work we are doing will help provide information about what's real and what's not. So there's the sort of reality-testing aspect that's important."

Link: http://websites.afar.org/site/PageServer?pagename=IA_spotlight_main

Then Why Not Compete For the Mprize?
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A discussion over at the Immortality Institute examines a question I'd like to see considered more often. If the latest overhyped offering from the "anti-aging" marketplace - or more reputable outgrowth of mainstream aging research focused on enhancing healthy longevity through metabolic manipulation - is so great, how come no-one is employing it as a part of competing for the $4 million Mprize?

It seems that there are lots of supplements with putative age prevention, cancer prevention, AGEs prevention, and heart disease prevention qualities. My question is: If these supplements help then why doesn't someone try them on mice.....? It seems that the M-Prize winners won from a single faceted approach: Growth hormone knock out, CR, Positive Enviroment etc... I understand the scientific value of testing one specific strategy at a time, but if someone is actually trying to win the M-Prize why not combine things?

...

Why doesn't someone take all the things which are more likely to increase lifespan than decrease it, and get the mice to take/do it?

The simple fact of the matter is that nothing presently out there in the marketplace - and I'll go out on a limb and say in the pipeline for the next couple of years as well - is going to do any better for already aged mice than calorie restriction, the currently winning technique for the Rejuvenation Prize aspect of the Mprize. The folk selling their "anti-aging" products are well aware of this fact, and so no-one is going to expend the hundreds of thousands or millions of dollars and couple of years to compete. As a marketing strategy, it makes no sense. As Brian Wowk puts it:

Perhaps you don't appreciate that almost every supplement sold is at best preventative, and doesn't actually impact intrinsic aging. I think M-Prize seeks to stimulate more fundamental interventions than just postponement of disease.

On the other side of the fence, it isn't likely that any mainstream funding source for aging research will go for the "let's try it all at once" approach that is presently popular on the sidelines. It's very hard to pick out the sort of results that get you published from a study on multiple forms of intervention running concurrently. That doesn't mean it isn't worth trying, but rather that no-one has yet been convinced of the return on investment for doing so: if mouse experiments are run rigorously in a scientific environment, the cost is certainly in the low seven figures.

For all that, as the Mprize continues to grow in size and influence, I would like it to come to be seen as the baseline for credibility in longevity medicine that moves beyond the lab and into development and commercialization. If you have something that works to extend healthy longevity, you should be demonstrating as such by competing for the Mprize, or pointing to past studies that have been entered into the Mprize. If you can't do that, you're not really serious.

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Inkjets and Bone Regrowth
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The Daily Mail illustrates the use of inkjet printing technology to fabricate scaffolds for bone regrowth: "The 'paper' in our printer is a thin bed of cement-like powder. The inkjets spray the cement with an acid which reacts with it and goes hard. That deals with one layer. Then new layers of fresh powder are sprayed on top, and the layers build up to the shape we need ... It takes only ten minutes for the printer, which is the size of about three filing cabinets, to print a typical bone graft. The printed graft acts as a bridge to allow the body to replace the damaged section with new bone. Crucially, the substance created by the printing process contains the same building blocks as real human bone, allowing the graft to eventually dissolve harmlessly into the body. The sections made by the printer are so precise that spaces can be left to encourage the regrowth of tissue and blood vessels through the graft, mirroring the make-up of normal bone. ... You can design it so you encourage it in a particular direction, to get different tissue repair. It is mainly useful in areas where you need a very good sort of fit, like cosmetic surgery or reconstructive surgery, or in the spine where you don't want to be playing around to get something to fit."

Link: http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=448654

The Methuselah Foundation Comes to Town
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Aubrey de Grey, Kevin Perrott, David Chambers and Damian Crowe of the Methuselah Foundation were in the Bay Area this week, advancing the cause of longevity research through a number of fundraising events. Much as the last time I met any of the Foundation folk in person, the week closed with a Saturday gathering of supporters on the topics of strategy, communication, near-term goals and organization. The nuts and bolts of getting things done, and done well, in other words. An eclectic group of folk from venture funding, media, aging research and non-profit interests kept the discussion from falling anywhere near to the normal fate for business topics on a weekend - very entertaining and informative, all in all.

As many of you have no doubt experienced in the past, keeping the wheels turning at best speed in a growing, changing organization is an interesting challenge. This is especially true in the non-profit space, where people are so much more driven by passion, and many of the key resources are volunteers. It is a testament to the intelligence and dedication of the volunteers and supporters of the Methuselah Foundation that they have surmounted each challenge to date, and that the organization continues to move forward apace to new goals in the grand plan.

In any case; it's no big secret that the Methuselah Foundation has until the end of 2009 to make the best of Peter Thiel's generous pledge of a $3 million matching fund. This means the clock is ticking on raising $6 million for SENS research: the combined sum of $9 million will be enough to fund a range of modest research programs, larger versions of those already underway and funded by the Foundation. That would be a good start, but the Foundation could be in a much better financial state than that three years from now if matters are well managed - expansion can be rapid indeed once you've established your credentials and potential for success. The path to growth is there, it just has to be executed on - this is also no big secret.

The prize for success at any level is a bigger, better, more rewarding mountain to climb!

I should point out an event on the Methuselah Foundation schedule from earlier this week hosted by the Alliance for Aging Research. I think it falls into the general spectrum of fundraising - there's much more to that game than knowing how to ask for money. A process of education and building relationships is absolutely essential:

Recent advances that harness the power of genetics, cell metabolism, nutrition and bioinformatics now make human aging itself a credible target for medical treatments. Whether today’s research succeeds in adding incremental years of health and vitality, or makes a quantum leap in human longevity, many believe that interventions will be deployed against aging in time to benefit current generations.

Will future drugs help protect against heart disease, cancer, diabetes, Alzheimer’s and other diseases by slowing the rate of aging? How will regulators measure the beneficial effects of age-retarding technologies? Will society readily adapt to medical treatments that improve life by a few years, or even by many years? Who are the scientific pioneers poised today on the leading edge?

An intriguing and provocative panel has been selected by Burrill & Company and the non-profit Alliance for Aging Research. You are invited to be among the select audience to hear presentations and pose questions to scientific leaders from two continents.

I'm told it went swimmingly.

There will be more presentations and fundraising events by Aubrey de Grey, other aging researchers supportive of the Strategies for Engineered Negligible Senescence, and the Foundation volunteers in the Bay Area in the months ahead. If you feel you can help make these efforts even more successful, why not contact the Methuselah Foundation and see about getting involved?

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A Part of the Smokescreen
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Real, actual anti-aging science - aimed at repairing the damage that causes aging - is largely obscured in the public eye by the smokescreen of the "anti-aging" marketplace, complete with flares and sirens. Much of it is nonsense or cargo cult imitations of real science, but the money and volume are such that it obscures the real scientific prospects for rejuvenation of the old in the years ahead. The better end of that marketplace is constantly on the verge of being more useful than damaging to the cause of healthy life extension - as Robert Butler points out in this New York Times article: "On the good side, it encourages healthy behaviors. On the other side, it sells things like human growth hormone, which is harmful." The article is, in general, a fair profile of the folk behind that nearly-of-net-benefit better end of the marketplace, Klatz and Goldman of the American Academy of Anti-Aging Medicine. They believe in what they are doing - it's unusual to find success in business on the part of those who don't - but I see precious little merit in most of their activities.

Link: http://www.nytimes.com/2007/04/15/business/yourmoney/15aging.html?pagewanted=print

The Long Road to Artificial Eyes
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The New Scientist reports on another small step on the long road to artificial replacement eyes. These are the days of slow, incremental work - but then the same was true of the internet 30 years ago. "Software that can be taught to refine the information sent from a bionic eye to its wearer is being trialled in Germany. ... These people report seeing light and dark and maybe some limited fuzzy shapes. But they don't have any gestalt perception. Eckmiller says the secret to improving these implants is to match the signals they produce with the signals that a healthy eye sends to the brain. One team in California, US, is trying to do that by building a copy of the retina's neurons in silicon. Eckmiller, along with colleagues Oliver Baruth and Rolf Schatten, plan to use learning software instead. ... It does this through a "dialogue module" that tries different settings while a user looks at standard shapes. The user selects the three settings that most closely match the real shape and the software then presents six more settings based on these three. Over time, the system learns to produce a signal that provides a more accurate picture to the user's brain. ... Currently the biggest challenge is to make a working device that interfaces with neurons properly."

Link: http://www.newscientist.com/article/dn11607-retinal-implant-learns-to-polish-the-picture.html

On the Hormonal Regulation of Aging
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Complementing the mainstream gerontological focus on genetic influences on aging is the study of the endocrine system, as illustrated in this paper: "Multiple biological and environmental factors impact the life span of an organism. The endocrine system is a highly integrated physiological system in mammals that regulates metabolism, growth, reproduction, and response to stress, among other functions. As such, this pervasive entity has a major influence on aging and longevity. The growth hormone, insulin-like growth factor-1 and insulin pathways have been at the forefront of hormonal control of aging research in the last few years. Other hormones, including those from the thyroid and reproductive system have also been studied in terms of life span regulation. The relevance of these hormones to human longevity remains to be established, however the evidence from other species including yeast, nematodes, and flies suggest that evolutionarily well-conserved mechanisms are at play and the endocrine system is a key determinant." The path to complete understanding is the slow path; it will make future therapies better and more effective, but we are already at the point of being able to make serious inroads in the fight to defeat aging.

Link: http://www.ncbi.nlm.nih.gov/pubmed/17360245

On the Genetic Regulation of Longevity
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A paper at PLoS Genetics gives a good idea of the present thrust of much mainstream aging research: genes, metabolism and the possibility of altering them for the better. "The lifespan of an animal is determined by both environmental and genetic factors, and many of the mechanisms identified to increase lifespan are evolutionarily conserved across organisms. ... We identified 64 genes that can extend lifespan when inactivated postdevelopmentally. More than 90% of the genes we identified are conserved from yeast to humans. Many of the newly identified longevity genes extend lifespan as robustly as the most well-characterized longevity mutants. It is possible that the homologues of these genes may also regulate lifespan in other organisms as well. Genetic analysis places some of these genes in known pathways regulated by insulin-like signaling, although many of these gene inactivations function independently of this mechanism of lifespan extension. Surprisingly, a subset of these gene inactivations that induce potent developmental arrest also facilitate enhanced survival in the arrested state, suggesting that aging at any stage may be subject to regulatory control."

Link: http://dx.doi.org/10.1371/journal.pgen.0030056

A Selection of Calorie Restriction Research
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There certainly is a great deal of published work coming out on calorie restriction and the related regulation of metabolism for greater health and longevity; funding for development based upon this field over the past year or two has no doubt further accelerated basic research. For all that I feel this ongoing metabolic examination and manipulation - aimed at slowing rather than repairing aging - is not the best path forward, it is still interesting work. Here are pointers to a couple of recent papers:

Ruminations on dietary restriction and aging:

Calorie restriction has been known for many decades to extend the life span of rodents. Since the more recent discovery that a long-term reduction in nutrient intake also extends life span in nearly every invertebrate model organism used for aging research, the mechanisms behind the longevity benefits of this intervention have been under intense scrutiny. While models have been developed in yeast, worms, and flies, the molecular mechanisms governing life span extension by calorie restriction remain controversial, resulting in great anticipation of mammalian studies testing these models.

Metabonomic Investigations of Aging and Caloric Restriction in a Life-Long Dog Study:

Long-term restriction of energy intake without malnutrition is a robust intervention that has been shown to prolong life and delay age-related morbidity. A 1H NMR-based metabonomic strategy was used to monitor urinary metabolic profiles throughout the lifetimes of control-fed and diet-restricted dogs. ... This analysis allowed the metabolic response to two different physiological processes to be monitored throughout the lifetime of the canine population and may form part of a strategy to monitor and reduce the impact of age related diseases in the dog, as well as providing more general insights into extension of longevity in higher mammals.

I mentioned the canine calorie restriction study a couple of days ago at the Longevity Meme; the calorie restricted dogs lived two years longer, on average. A more informative article for the layman turned up yesterday in the Economist, illustrating the thrust of the research in terms of metabolic rates and bacterial processes:

Choline is made available for absorption from the intestine by the activities of the gut bacteria that are liberating it for their own purposes. The amount of aliphatic amines in urine is thus an indirect measure of how much choline is available. As in the case of creatine, this differed between the two groups. Dogs on the restricted diet had lower levels of the amines in their urine than did their well-fed counterparts - implying that less choline was being made available. And if less choline were available, that would limit a dog's ability to metabolise fats, and thus restrict its metabolic rate.

The apparent drop in choline levels was much greater than could be accounted for by a relative lack of food, so Dr Nicholson suspects that the restricted diet was also causing the composition of the dogs' gut flora to change in a way that did not favour choline-munching bugs.

Moving on, a couple more papers further reminding us that calorie restriction makes a difference for most age-related conditions:

Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease:

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with the neuropathological hallmarks amyloid beta-peptide (Abeta) plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, we tested the hypothesis that two different energy restriction regimens, 40% calorie restriction (CR) and intermittent fasting (IF) can protect against cognitive decline in the triple-transgenic mouse model of AD ... We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies.

Different gene expression of skin tissues between mice with weight controlled by either calorie restriction or physical exercise:

Cancer prevention by weight control via dietary calorie restriction (DCR) and/or exercise has been demonstrated in animal models. To understand the underlying mechanisms, we compared phorbol ester (TPA)-induced gene expression profiles in DCR- or exercise-treated mouse skin tissues. SENCAR mice were randomly assigned to one of the following groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AE), exercise but pair-fed at the amount of the control (PE), and 20% DCR.

...

The results of 22 cancer-related gene expression patterns, especially for certain oncogenes, further supported that PE appeared to be a better alternative than AE to DCR-like cancer prevention. The impact on gene expression pattern was associated with the effect on weight loss (i.e., DCR >> PE > AE). Overall, this study demonstrated for the first time that weight control via decreasing energy intake or increasing energy expenditure resulted in the different modes of gene expression. DCR showed profound inhibitory impact on the expression of genes relevant to cancer risks. Furthermore, exercise along with limited calorie intake appears to be a better method for reducing weight and cancer risk compared with exercise alone.

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The Proteomic Approach to Aging Research
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This paper is a reminder of the power of modern biotechnology to pull information from our biochemistry. Want to learn more about aging? Why not start by building a database of changes in levels, usage and alterations in every protein in the body with age? "The scope of the current paper is to review existing and potential applications of proteomic analysis to aging research. The focus will lie on the unique opportunities of high-throughput studies for uncovering specific alterations in protein expression, protein complexes or protein modifications caused by biological aging. The result of such studies will outline aging phenotypes and potentially indicate pathways involved in the pathogenesis of age-associated disfunctions. Specific attention is paid to the illustrations of successful applications of proteomic technologies and potential applications of new proteomic concepts to biogerontological studies." The rate at which scientists can build such a database is presently far in advance of the rate at which they can extract meaning from it, but that's no reason not to get started.

Link: http://www.ncbi.nlm.nih.gov/pubmed/17425465

Longevity, Economics and Other Motivations
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Thoughts from Anne C.: "It might be necessary, at times, to invoke primarily economic arguments when dealing with people whose own main argument in opposition to healthy life extension is that "older" old people will decrease the amount of resources available for activities not related to health crisis management. Here, the economic argument is appropriate in the sense that it corrects what is more than likely factually untrue from an economic standpoint -- it is obvious that if a person doesn't get heart disease, nobody is going to need to spend any money to treat heart disease in that person, which means that money is free to be used elsewhere. But the reason we want to prevent heart disease -- at least, the primary reason -- isn't an economic one, but one that I hope stems from compassion. Heart disease left untreated will most likely kill you. Aging left unaddressed will definitely kill you, whether indirectly or directly. So of course I'm in favor of things like longevity research -- because it has tremendous potential to save many, many innocent lives. Sure, it might end up having a particular economic effect that will make some people happy, but even if there was no chance of that, I would still support such research."

Link: http://rationallongevity.blogspot.com/2007/04/longevity-disability-and-economic_11.html

More On TA Sciences, TA-65
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Following up on a post from earlier this week, I thought I'd direct your attention to a discussion on the anti-aging hype of TA Sciences, TA-65 and Astragalus over at sci.life-extension. Many hands make light work, and the folk there have laid out a lot more of the background via additional resources.

Those are some interesting studies, but the most I can glean from them is that astragalus appears to have some antioxidant and immunomodulatory effects in vitro and possibly in vivo, according to a few articles published in some obscure Chinese med journals.

This of course is a far cry from being a "telomerase-inhibiting anti-aging supplement that improves skin quality and enhances male sexual function".

...

http://www.tasciences.com/ta/blum.html

Did you see those p-values?? Almost *none* of them is statistically significant (i.e. p is less than or equal to 0.05)

There are some interesting trends, but this certainly doesn't cut it as far as scientific evidence.

...

That plus what exactly was measured is not exactly well specified. There is a slightly more detailed version linked at the bottom but still...

My conclusion still stands, I think:

It reminds of the pitch for Protandim; a little piece of interesting scientific research stretched out thin as possible to cover a cartload of marketing for herbal compounds. ... So here we have the same old marketing nonsense, dressed up in flashy scientific clothing to give it the veneer of legitimacy. Same old attempts to adopt the form of science without the substance of science, the same old corrosive misinformation and look and feel games.

I can't see much good coming of this for Geron; this sort of partnership doesn't reflect well on a research company.

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Revisiting Calorie Restriction in Dogs
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From Chemistry World, a look at a canine calorie restriction study: "48 puppies from seven litters were raised at a research centre in the US ... Animals were fed either a restricted or normal (control) diet and subjected to regular clinical assessment. Urine samples collected from each dog during these check-ups provided a metabolic record that UK scientists have used to study the biological process of aging and metabolism. The dogs on the restricted diet lived about two years longer than those on the control diet. The last of the dogs died just over two years ago, and [researchers] have now used updated analytical techniques on the old samples to measure life-long biochemical changes. ... levels of gut microbial metabolites, like methylamines, cresols and other aromatic compounds, were different between the two groups of dogs. ... This is significant because altered gut microflora has already been linked to obesity in humans." An interesting fact to add to the list of changes wrought by calorie restriction, and a good comparison to the ongoing primate studies.

Link: http://www.rsc.org/chemistryworld/News/2007/April/11040701.asp

Liver Regeneration Easier Than Thought?
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EurekAlert! reports that some researchers are optimistic about enhancing liver regeneration: they tested "whether regenerating cells behave like embryonic ones, as is commonly assumed for other organs. New processes may explain why the liver is so uniquely capable of renewal and repair after injury, the scientists thought. ... The results were unexpected. The researchers noticed that only a few proteins were common to both processes. Proteins called transcription factors, which affect DNA in the cell's nucleus, were highly involved in the development of embryos' livers but not in adult liver regeneration. Instead, proteins that help cells proliferate were active in both the developing and regenerating livers. These findings showed that a regenerating liver does not behave as a developing embryo. Instead, regeneration could actually be only due to an increase in cells that multiply through regular cell divisions, a process called hyperplasia. ... Not only did we discover that the number of proteins involved in liver regeneration is relatively low, but they don't include transcription factors, so we may be closer to being able to stimulate liver regeneration than we thought."

Link: http://www.eurekalert.org/pub_releases/2007-04/asfb-lrm041107.php

A Little Friendly Cooperative Competition
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It's good to see the Singularity Institute for Artificial Intelligence (SIAI) growing and progressing at a fair pace. Recent announcements include a slew of new faces in new positions, including Ray Kurzweil for their board of directors, and a $400,000 matching challenge funded by Peter Thiel:

In the coming decades, humanity will likely create a powerful artificial intelligence. SIAI exists to confront this urgent challenge - the opportunity and the risk. We have built the infrastructure to expand our research, education, and outreach initiatives in 2007. Thanks to the generous support of our matching fund donors, we are announcing the $400,000 Matching Challenge, which, if successful, will help underwrite our expansion this year.

...

The ideas of a singularity scenario and Friendly AI are powerful, but more importantly, relevant now. I support SIAI because they are making unique contributions to these critical areas of knowledge. I have pledged $200,000 in matching funds to the matching challenge to help grow the Singularity Institute, with an additional $50,000 available if half of the challenge is matched in the first 45 days. I hope you will join me as a donor, and support this important organization.

SIAI is probably the closest thing to a friendly competitor to the Methuselah Foundation, given that they knock on many of the same doors in search of funding and support. Competition is always a good thing between friendly parties - it keeps us on our toes, reaching for better results, and improves the rate at which fundraising strategies can be explored and refined. I'll be happy to see the two sides of the fence spur one another to greater effort and greater progress.

Given the long-standing connections between the forward-looking segments of the strong artificial intelligence and healthy life extension communities - the transhumanist community and friends, in essence - it's only natural that two of the most successful organizational outgrowths of those communities should be on such good terms.

It has come to pass, as such things often do, that the Singularity Institute and the Methuselah Foundation share major donors, there is an overlap of volunteers and supporters, important members have known one another for years and on, and key fundraising operations are held in much the same geographical locations these days. Should you wander into a strategy meeting for one organization, it might take a few moments of counting heads to work out which of the two it is. All the better to gently remind one another of the latest successes...

I am happy to say that 138 people and organizations have joined The Three Hundred since its launch, and each is helping to change the world for the better by funding the Mprize for longevity research and the SENS science sponsored by the Methuselah Foundation.

We're well on the way to filling half of the places in the The Three Hundred, and what a milestone that will be!

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Explaining ApoE4
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The Oklahoma Medical Research Foundation reports on new understanding of the role of ApoE4 in the development of Alzheimer's: "ApoE4 (along with other apolipoproteins) attaches itself to a particular receptor on the surface of brain cells. That receptor, in turn, adheres to a protein known as amyloid precursor protein. The brain cells then transport the entire protein mass inside. Once inside, cutting enzymes - called proteases - attack the amyloid precursor protein. These cuts create protein fragments that, when present in the brain for long periods of time, are believed to cause the cell death, memory loss and neurological dysfunction characteristic of Alzheimer's. ... this new study is the first to connect the process of protein fragment formation to ApoE4. ... ApoE4 apparently interacts better with the receptor than its cousins. This may explain why people who carry the E4 gene have a higher risk of developing Alzheimer's." Differences in susceptibility can be used to discover biochemical mechanisms in just this way - and knowing the mechanisms in this day and age is a fast road to interfering in their progression.

Link: http://www.omrf.ouhsc.edu/OMRF/News_Releases/Releases/2007/20070410.asp

More On Rebooting the Immune System
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I've pointed out work on systematically destroying and recreating an immune system, so as to remove life-threatening damage or errant behavior. Here, the New Scientist reports on a practical demonstration of the technique: "recruited 15 people aged 14 to 31 years who had recently been diagnosed with type 1 diabetes. Roughly 60% to 80% of these patients' insulin-producing cells had been destroyed [by their own immune system] by the time of their diagnosis, and all needed regular insulin shots. The researchers removed bone marrow stem cells from the patients, who were then given drugs such as cytotoxan to wipe out their immune cells. Without an immune system, the patients were vulnerable to infection and so they were given antibiotics and kept in an isolation ward. ... Two weeks later, the patients received infusions of their own stem cells into their bloodstream via the jugular vein, which re-established their immune systems. ... Of the 15 patients, 12 no longer needed insulin shots within a few days of undergoing the procedure." How beneficial could this sort of strategy be for an aged immune system, choked by a buildup of useless cells devoted to fighting non-threatening chronic infections?

Link: http://www.newscientist.com/article/dn11571-rebuilt-immune-system-shakes-off-diabetes.html

Illustrative of the Tone of the Conversation
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Continuing yesterday's theme on the protective coloring adopted by entrepreneurs in the "anti-aging" marketplace - sound sufficiently like a scientist and you might just fool enough people to get wealthy - I though I'd point out a slightly more subtle example today in the person of Sanjay Gupta.

Many books offering health advice focus on a single area. They may tell you how to keep your brain healthy or how to maintain peak fitness or how to lower your stress or how to sleep better. Some of these books are very good, but common sense tells us that we need a balanced approach between diet and lifestyle. In this book, I will try to offer that. I will also try to make this book a clear and concise guide that rises above the clutter.

Some of the advice may surprise you. For example, physical fitness can have a profound effect on your cognitive abilities later in life, and your mental outlook could have a profound effect on your long-term physical health. Taking lots of supplements, as many experts recommend, may not be effective whatsoever. Eating a low-calorie diet could trigger a cellular reaction that leads to a cascade of events ultimately leading to longer life. How much exercise and what kind you do can make a difference. Eating foods like dark chocolate and dishes containing the spice turmeric and drinking red wine, green tea, and even coffee can all help you live longer and healthier, with a dramatically sharper mind.

Many in the scientific community are thinking about ways to alter the human life span. They are imagining great leaps in understanding aging and dreaming up ways to counteract it. In their brave new world science, we will be able to replace worn organs the way you replace the worn brakes on a car; special enzymes or genetic therapies will rejuvenate our cells; microscopic nanobots will circulate through our bodies, warning of future health problems, which can then be addressed. Researchers are predicting stem cells will someday prevent such degenerative diseases as Alzheimer's and Parkinson's. These therapeutic advances could shatter what we now consider a human life span, extending it by decades or more. Ray Kurzweil, a futurist and inventor, thinks scientific progress is advancing so quickly, we will all be able to live forever -- if we can only make it a few more decades.

Despite the flurry of activity in labs across the developed world, there is no magic elixir yet, leaving those of us who want to live longer, healthier lives to use the best information currently available as guideposts. Of course, there are no guarantees. People who live lives that are paradigms of clean living succumb to cancer, and others who spend years ignoring the best advice of doctors and others live into old age. After all, Jeanne Calment reportedly didn't give up smoking until the age of 117.

Which all sounds eminently reasonable; talking about science, stem cells, calorie restriction (and name-dropping Ray Kurzweil). But the bottom line is this is another fellow whose advice is much along the lines of "be happy, eat and exercise the fad of the moment" - which Ray Kurzweil is just as guilty of, frankly:

Instead of eating fast food and drinking way too much soda, we should be eating what Gupta calls "power foods" - foods that have Omega 3, antioxidants, fiber and vitamin value, such as fish, cauliflower and blueberries. And we should also consume foods with high water content, like watermelon.

"That lets you increase the volume of what you eat while lowering the calories. You are eating more food and fewer calories at the same time."

To make sure we get it right, Gupta suggests we "treat our bodies like templates and eat seven different colored foods a day."

...

"Attitude towards life makes a big difference in how you feel," says Gupta, adding, "people who are happy and successful tend to live longer than people who aren't."

This is the core of it, and all the rest is just a film of scientific knowledge, culled from what researchers are presently saying, and used to convey legitimacy. All part and parcel of making some money from being somewhat well known. There's nothing mysterious about good health practices, and many, many starting points for understanding how eating fewer calories while obtaining optimal nutrition is good for you; it's all common sense, easily researched in this day and age of the internet.

Does this sort of thing wind up doing more good than harm? Is the message of "eat this, drink that and live longer" waking folk to the far greater future possibilities of longevity science, or does it simply lull them into thinking there is nothing beyond supplements and optimization of diet?

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Uploading 101
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Looking more than a single step ahead at the IEET, a gentle introduction to attaining extreme longevity through copying ("uploading") the mind into the computer hardware of tomorrow. "We are going to want to store our brain in a permanent medium. That is where this whole idea of mind uploading comes from. Back up our consciousness and run it on another medium where we don't have 30 million neurons dying every year. ... There are maybe ten to twenty different commonly discussed possible ways to do this. ... The second way is neuron simulation of some sort. You have to somehow get inside the brain, probably destructively, and look at every single neuron and see how is it connected to all the other neurons around it, how are the synapses weighted, how are the synapses connected, and somehow tease that out of the structure. ... The thing that is so interesting is that all of these things are probably possible, perhaps within 40 years." The points made on the speed of progress and our unwillingness to recognize this speed are good. It may turn out to be more efficient in the end to radically change our bodies and minds than to keep repairing what we have. But uploading as commonly presented strikes me as an expensive form of procreation - your copy will live a long, long time, but you'll be stuck exactly where you are. Or destroyed in the copying process, under some schemes.

Link: http://ieet.org/index.php/IEET/more/brain20070409/

Another Candidate For Gender Longevity Differences
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The much debated difference in longevity between human genders might be due to differing levels of stem cell effectiveness. From EurekAlert!: "Female stem cells derived from muscle have a greater ability to regenerate skeletal muscle tissue than male cells ... Regardless of the sex of the host, the implantation of female stem cells led to significantly better skeletal muscle regeneration. Based on these results, future studies investigating regenerative medicine should consider the sex of the stem cells to be an important factor. Furthermore, investigations such as ours could lead to a better understanding of sex-related differences in aging and disease and could explain, at least partially, the high variability and conflicting results reported in the literature on stem cell biology. ... [researchers] injected female and male muscle-derived stem cells into dystrophic mice and [then] calculated the regeneration index (RI) ... Only one of the 10 male populations of implanted stem cells had an RI over 200. In contrast, 40 percent of the female stem cell populations had an RI higher than 200, and 60 percent of the female populations of stem cells had an RI higher than the mean RI of the male cells (95)."

Link: http://www.eurekalert.org/pub_releases/2007-04/chop-tss040407.php

TA-65: The "Anti-Aging" Marketplace At Its Terrible Best
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Looking at this press release, I have to wonder if the folk at Geron know what they've letting themselves in for, partnering with these TA Sciences people and their TA-65 product.

Looking around the TA Sciences site (via Google, since they don't link much from the home page), the FAQ makes it much more clear what they're up to - selling herbs, essentially - and just how deceptive the uber-scientific cover and hyping of telomeres and telomerase is for that activity. It reminds of the pitch for Protandim; a little piece of interesting scientific research stretched out thin as possible to cover a cartload of marketing for herbal compounds.

TA Sciences follows stringent scientific procedures to back up the safety and efficacy of our products. Over the last four years we have conducted a series of studies including, most importantly, the Pivitol 2005 Anti-Aging Trial designed to directly measure the effect of TA-65 when taken internally. In this trial we saw a clear reduction in the signs of aging from the introduction of TA-65 into the bloodstream.

...

TA-65 is a naturally occurring molecule found in the ancient Chinese herb Astragalus. Well known to most of China's 1.3 billion people for over 1000 years, Astragalus root can be found in every traditional Chinese herbal shop. Major health benefits from this plant have long been recognized by practitioners in China, but never before has the TA-65 active ingredient been isolated and purified.

"Clear reduction in the signs of aging," if you read the footnotes, is parsed out into a vague statement on telomerase activity which means nothing of the kind. So here we have the same old marketing nonsense, dressed up in flashy scientific clothing to give it the veneer of legitimacy. Same old attempts to adopt the form of science without the substance of science, the same old corrosive misinformation and look and feel games. To that end, Geron are going to see their name mentioned every other word for so long as it drives sales to the gullible.

Don't be duped - if these people were selling anything worth buying, they wouldn't be draping it in shiny, shiny gauze and otherwise acting like every other shyster at the dubious end of the "anti-aging" marketplace. Your choice is of course your choice, but why make life easier for the people who make it harder for legitimate longevity research to obtain support and funding?

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Narrow and Incremental
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CNN takes a look at the commercial end of the stem cell research and development pipeline: "Two biotechs, Cytori Therapeutics and Osiris Therapeutics, each hope to get their experimental stem cell products approved by the Food and Drug Administration and into the U.S. market by 2008. ... Cytori is planning to launch its first stem cell medical device in Europe this year [using] stem cell technology to rebuild breast tissue in cancer survivors. ... Osiris, [currently] has the only stem cell-based product that's been approved by the FDA. OsteoCell, which stimulates bone growth and is already on the U.S. market, is actually considered an implant rather than a drug or device. ... Prochymal, a potential treatment for acute Graft vs. Host Disease (also known as GVHD) and Crohn's disease, is in late-stage trials." Applications are narrow, incremental and slow in coming because the regulatory regime forces development in this direction; this becomes the cost-effective path, rather than anything more ambitious.

Link: http://money.cnn.com/2007/04/05/news/companies/stemcell/index.htm

More Science From the Edmonton Aging Symposium
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Over at the Methuselah Foundation blog, LysoSENS researcher John Schloendorn provides a report on the recent Edmonton Aging Symposium: "Progress has been solid and steady in the other fields pertaining to the removal of age-related damage according to the SENS proposals: Too few cells, and too many cells, and the three types of junk (inside cells, between cells and protein crosslinks). The cellular work featured Conboy and Conboy from Berkeley, pioneers in investigating the role of how an aged bodily environment dictates the aging various stem cell types, and presented excellent data with implications on how one might go about shielding the stem cells from this influence. This might one day allow the stem cells in an aged person to ignore the body's calls to stop regenerating ... Judith Campisi [attempted] to get rid of unwanted cells [and] reported on overcoming matrix metalloproteinases, an important mechanism by which such senescent cells can defend themselves against immune cells attempting to clear them out. ... In the field of age-related storage diseases, atherosclerosis researcher Jay Jerome explained the need for enzyme therapies to resolve arterial plaques, and Rittmann showed how his Methuselah Foundation-funded work to clone suitable enzymes from environmental microbes has made excellent progress over the past year."

Link: http://blog.methuselahfoundation.org/2007/04/john_schloendorn_reports_on_th_1.html

Exercise and the Aging Brain
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Letting yourself slip into a sedentary lifestyle is going to put a dent in your life span, future health and wallet; why dramatically increase your chances of being sick, miserable, beset by huge medical bills (and dead before your time) if there are simple things you can do now to improve your outlook? Common sense on the way in which exercise improves long-term health prospects is continually reinforced by the output of the scientific community. Here are a couple more recent papers on the subject, with a focus on exercise and brain function.

Physical Activity and the Risk of Dementia in Oldest Old:

OBJECTIVE: This study evaluated the protective role of physical activity (PA) against cognitive impairment (CI) in the oldest old (age >/= 85).

METHOD: Prospective data on 66 optimally healthy, oldest old adults (mean age 88.5) were analyzed using survival analysis.

RESULTS: In all, 12 men and 11 women reported exercising > 4 hours per week, and 38 participants developed CI (mean onset age 93; mean follow-up 4.7 years). The effect of exercise was modified by gender. In more active women (> 4 hours/week), the risk of CI was reduced by 88% (95% confidence interval 0.03, 0.41) compared to those less active. Less active women had 2 times the incidence rate of CI compared to less active men and almost 5 times the rate compared to active women.

DISCUSSION: This study demonstrates the beneficial effects of exercise on healthy brain aging even in the oldest old and emphasizes the importance of increasing PA in older women.

Nothing is immune to abbreviation when you're trying to cram information into an abstract, as you might have noticed. But look at this - billions of dollars will change hands in the development and commercialization of therapies that change the degree or rate of specific outcomes by 30%, never mind a factor of 2 or 5. The value of looking after your own health in basic, easy ways is enormous. Yet people don't do it.

Role of aerobic fitness and aging on cerebral white matter integrity:

Neuroimaging research suggests that cerebral white matter (WM) integrity [is] decreased in older adults, especially in the prefrontal regions of the brain. Behavioral investigations of cognitive functioning suggest that some aspects of cognition may be better preserved in older adults who possess higher levels of aerobic fitness. There are only a few studies, however, investigating potential mechanisms for the improvements in aerobic fitness. Our study suggests that greater aerobic fitness may be related to greater WM integrity in select brain regions.

In past times, one might shrug and suggest that a decade here or there makes little difference, given that the final destination is same, and that getting the most out of the time allotted is a good primary focus. That sort of economic calculation is obsolete, however, made so by the prospects for healthy life extension within our lifetimes. The rapid advance of biotechnology opens up the possibility that a sudden expansion of healthy life expectancy - due to our increasing ability to repair the biochemical damage of aging, and thus rejuvenate the old - will happen over the course of a few decades, and that those decades could soon arrive. Ten years here or ten years there in your present life expectancy suddenly looks like a very big deal - the difference between death or healthy life for centuries, floated on ever more capable longevity medicine.

So take care of the health basics. They could make a long, long difference to your eventual span of healthy years.

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Medical Tourism Illustrated
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Medical tourism brings in resources that allow researchers in locations such as India and Thailand to test new therapies. It's all very much caveat emptor, as for any buying decision, but the end product of this industry informs more rigorous and costly development. Take this news from MedIndia.com: "A premier hospital in the southern Indian state of Karnataka claims to have made a major breakthrough in the treatment of Parkinson's disease utilizing the stem cell therapy. ... the patient's bone marrow was harvested at the regenerative medicine department and the mesenchymal stem cells were injected into the part of the brain, which was affected because of Parkinson's disease. ... The successful recovery of the patient would give hope to scores of Parkinson's cases which affects one per cent of the population. ... However, we need to observe the long term clinical effects in larger number of patients to decide whether it is primary or secondary or supplementary treatment option for degenerative disorders."

Link: http://www.medindia.net/news/view_news_main.asp?x=19777

TransVision2007 Coming Soon
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The Transvision2007 conference will be held July 23rd to 26th in Chicago, IL. The organizers "urge you to register soon, as we will fill up and will cut off registration once we reach capacity. If you register by Sunday, April 15th, you will receive a $200 discount off of the regular registration fee. So don't wait. ... the theme of TransVision 2007 is: Transhumanity Saving Humanity: Inner Space to Outer Space, and will feature three full days of compelling dialogue with the greatest minds of today about creating the civilizations of tomorrow. TV07 brings extraordinary people from across the globe together with more than 30 distinguished speakers, entertainers and visionaries including: award-winning inventor, futurist, author Raymond Kurzweil; acclaimed longevity scientist, Aubrey de Grey; and Emmy award winning actor, William Shatner." The pre-conference event is entitled "Securing the Longevity Dividend" and includes presentations from S. Jay Olshansky and Aubrey de Grey with a policy focus aimed at "scholars and journalists interested in the future of aging and healtcare; legislative aides and policy makers considering Longevity Dividend as a policy program; pro-longevity, health care and senior activists interested in building the Longevity Dividend campaign."

Link: http://transvision2007.com/

Video From the Edmonton Aging Symposium
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A couple of the presentations from the Edmonton Aging Symposium have already found their way to Google Video:

The Stock-Callahan debate attracted some attention from the media already - now you can see what you think of the source material. I've always found it curious that talking about the merits and reasons for action garners more notice and spilled ink from the mainstream media than actual plans for action, never mind the action itself. People will talk themselves blue before writing a blueprint or raising a finger, and seem to find that talk more interesting than the end result, but I'm sure you're all familiar with that aspect of human nature.

Much more video will be forthcoming in the days ahead as it is approved by the presenters.

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Towards Regenerative Cures For Deafness
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Via ScienceDaily, a snapshot of progress towards regenerating the loss that causes one type of deafness: "researchers have isolated 'cochlear stem cells' located in the inner ear and already primed for development into ear-related tissue due to their proximity to the ear and expression of certain genes necessary for the development of hearing. ... Previous work in our lab with young-adult mouse cochlear tissue showed expression of genes normally found in stem cells and neural progenitors. This led us to hypothesize that cochlea harbors stem cells and neural precursor cells. Our work in collaboration with Miller's lab supports our hypothesis ... Clearly we have miles to go before we reach our end goal, but the exciting part is now we can test compounds that could promote regeneration of hair cells from these precursor cells in vitro, we can study the genes expressed during the transition from stem cells to hair cells, and we can think of developing strategies for cell replacement, i.e. transplanting these cochlear stem cells into the adult cochlea to affect hair cell replacement in the mouse, by extension, in humans."

Link: http://www.sciencedaily.com/releases/2007/04/070405170200.htm

From Around the Blogosphere
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A few posts of interest caught my attention today, starting with a discussion of health, free radicals, oxidative stress and aging from Anne C.:

Many health-oriented sites on the Web and popular magazine articles and books will emphasize the role of nutrients, diet, and moderate exercise in promoting longevity. If you follow the advice from the better sources in that particular pool of information, you might indeed end up gaining yourself a few extra years of health in old age. But when I think of "longevity", I don't think in terms of "living to age 80 and still being able to play golf", as most of the aforementioned sources probably do. I think in terms of "living to age 80 and not having to worry about increased risk of cancer, immune collapse, organ failure, heart disease, atherosclerosis, Alzheimer's, or any number of other things that have long resulted in pain and death for people in your age group". Why should any group of people be expected to just accept pain and death, particularly on account of a factor as ludicrously arbitrary as how old they are?

Especially now that we're moving into an age in which we can engineer a material difference to the impact of aging on the human condition. Why sit still when there are the medicines of longevity to be built, when the biochemistry of aging awaits human understanding? These are the years of the biotechnology revolution, and we can enact great change in health and longevity if we but set ourselves to work.

Moving on, Attila Chordash posted a reminder late last month on the complexities of biology. Stem cells are not always stem cells, and the populations of stem cells in our bodies are much more dynamic and varied than might be convenient for the advance of regenerative medicine:

It has long been suspected that cells other than those that maintain homeostasis (actual stem cells) can take over stem cell function in certain situations, and they have been referred to as potential stem cells ... Indeed it seems that transit-amplifying progenitor cells are potential stem cells in this system and when actual stem cells are lost due to an injury or perhaps naturally over time, the remaining progenitor cells or progenitor cells acquired by transplantation have the potential to acquire stem cell functions.

A constantly changing system of many parts is harder to understand and manipulate. If stem cells in any given tissue come in several flavors, changing over time in their biochemistry, then that will add additional time and cost to the cycle of research and development. Success is inevitable, but we should not become careless and assume that success will occur in time to help us fight our age-related degenerations. All the more reason to become involved and support medical research!

Bioethicist Daniel Callahan's comments at the Edmonton Aging Symposium caught the attention of folk at Samizdata, who called out a few of the necessary responses:

Callahan's bioethics appears to be a code for denying individuals choice on the grounds that society has more urgent goals

...

Aging kills about 100,000 people per day worldwide. Do we have any other problems as "pressing" as something that kills people at that rate?

If our funding decisions today bring the eradication of aging just one year closer, that would save the lives of a larger number of people than the population of Canada.

And who on Earth is he to say that the individual desire to avoid death "is not legitimate"?

...

I actually agree with Dr Callahan. He is absolutely 100% right and that is why healthcare should be privately funded. After all, if I spend my cash on being able to celebrate turning eleventy-one and am fit enough to break-dance on the occasion then what business is it of the esteemed Dr?

...

There is a fundamental problem with what M.r. Callahan is saying, all my other qualms with his words stem from it: He implicitly assumes, through the way he makes his case, that funding and research are somehow things that must be centrally directed by tax funded research. By saying "we" he's really talking about the state funded institutions and laboratories, and in case he's not, then he's certainly assuming that what research is done will surely be conducted with centralized direction. This is a commonly occuring blindness in social debate of any kind. First of all, as far as numerous sources of private research and funding go, its none of his business. Whether trying to reverse aging is legitimate or not is entirely a subjective choice of whomever decides to or not to fund it.

Without choice and freedom, what is left? Too many people in this world are all too ready to condemn their fellow travelers to shackled lives, forced into directions they would not have chosen. And to what end? There is something wrong with that part of the human mind that leads us to this state.

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Science at the Edmonton Aging Symposium
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One of the scientists attending the Edmonton Aging Symposium talks about the event at Ouroboros: it "was an interesting mix: scientists from all over the interdisciplinary field of aging research, and educated laymen who have a keen interest in our work. ... Irina Conboy (my boss) presented our lab's currently in-press data on how an aged tissue environment negatively affects the ability of muscle stem cells to differentiate. The proximity of [embryonic stem cells], however, can locally rescue the affects of a 'polluted' niche. We are currently investigating the soluble factors that regulate the ability of cells and tissues to renew and regenerate. ... Ellen Heber-Katz gave an update on the MRL (Murphy Roths Large) mouse story. She has discovered that this regenerating mouse breaks down the basement membrane in the vicinity of an injury (apparently similarly to other, more 'traditionally' regenerating creatures such as salamanders). Matrix metalloproteinases secreted by inflammatory cells recruited to the wound site are apparently essential to this aspect of the healing process."

Link: http://ouroboros.wordpress.com/2007/04/06/conference-report-the-edmonton-symposium-on-aging/

More From the Edmonton Aging Symposium
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From The Gateway, another report from the recent Edmonton Aging Symposium: "held at the University of Alberta last weekend, [the symposium] brought together 37 top scientists, academics and theorists from around the world to take a look at the science and ethics of aging. This conference explored the possibility that the detriments of aging are no longer unavoidable, and that technologies capable of drastically extending the human lifespan are almost within reach. ... 'It's very probable that the first person to live to 1000 will be less than 20 years younger than the first person to live to 150,' de Grey suggests. Although this claim may seem surprising, [the] feat of doubling life expectancy has already been accomplished in one lifetime. ... At the turn of the century average life expectancy was somewhere around 39 ... now it is much older, [around 80 years old] ... The logic of [a 1000 year lifespan] is actually much more certain and much more incontrovertible than any of the more near-term stuff that I talk about - which is, after all, the nuts and bolts of how to get there in the first place - and yet it's the discussion of four-digit lifespans that really gets people upset."

Link: http://www.thegatewayonline.ca/the-fountain-of-youth-20070405-528.html

Calorie Restriction Research Roundup
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As Chris Patil notes, "The calorie restriction (CR) literature is exploding: dozens of papers are published each month, many of which are noteworthy in some way. ... Calorie restriction in adult men and women causes beneficial metabolic, hormonal, and functional changes, but the precise amount of calorie intake or body fat mass associated with optimal health and maximum longevity in humans is not known ... Fertility was not altered by CR in any of the examined groups. ... This preliminary study encourages speculation that mild regimens of CR can produce health and longevity benefits without the 'costs' of impaired reproductive potential. ... These observations combined with the recent suggestion of active alterations in aging processes by antiaging genes do suggest the potential for significant beneficial effects of CR in humans consistent with the effects that are emerging in the nonhuman primate studies. However, some theoretical analyses alternatively suggest that there may be only a limited potential of CR to extend lifespan and reduce morbidity in humans."

Link: http://ouroboros.wordpress.com/2007/04/05/research-roundup-calorie-restriction-unlimited/

Wisdom From the Readership
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I felt obliged to share this pearl with you folk, emailed by HH the other day:

A lot of people say, "Who wants to live to be 80?"

They keep on saying it until they are 79.

So very true; here's an example from a youngster of 22 from the past week:

But after listening to Dr Daniel Callahan, international program director of The Hastings Center (a bioethics think-tank), I for one am not convinced that money spent on longevity research couldn’t be better spent elsewhere. After all, there are very few compelling reasons for extending life spans, and a multitude of negative repercussions if we do.

...

All things considered, the prospect of extending my life an extra ten years or so isn’t really appealing - not necessarily for personal reasons, but for the impact that it would have on those around me. Who would be expected to take care of me for another decade?

Where is the foresight? Where is the planning, evident in saving for financial security in later life, yet so very absent when it comes to the security of your health? I've said it before, but I think it merits saying often:

The lifestyle choices most likely to dimish your health, shorten your life and leave you more frail and suffering in old age - not to mention poor, broken by the cost of therapies - are no big secret. ... Yet still, the majority of the population in more comfortable, wealthy locations in the world persists in indulging. Such is the power of choice, and the consequence of that primate-scale level of time preference we humans have inherited. We've all stolen quality and years of life from the person we will be in future decades - and some of us just keep on doing it right up until we're living (and dying) in the pocket we once picked.

The disconnected observer might suspect that most people are eagerly engaged in plotting the misfortune, illness and demise of their future selves. At this point, our inaction in the face of great opportunity in biotechnology research, and easy means to support meaningful longevity science, is doing far more damage than the overeating and lack of exercise.

This must change if we are not all too soon to be old and broken, looking back and cursing our younger selves for fools whilst suffering and dying from age-related degenerations of the body and mind.

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New York State To Fund Stem Cell Research
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(From Science). Following on from my last note on the topic, it looks like public funds will be directed to stem cell research in New York: "On the night of 31 March, minutes before the beginning of the state's 2008 fiscal year, legislators passed a budget that includes $100 million for stem cell research. The money will be administered by a new entity set up within the state health department. In addition, for the next 10 years, the state will provide up to $50 million annually for stem cell research from a fund created from the sale of state-run insurance plans to private entities. In addition to [this], stem cell supporters are optimistic that the legislature will appropriate an additional $50 million a year. ... The law calls for the establishment of a 13-member Empire State Stem Cell Board to be appointed by the governor, which will administer the new Empire State Stem Cell Fund for research in the state. ... the board will set up panels of outside scientists - most likely not from New York - to review the grants."

Link: http://sciencenow.sciencemag.org/cgi/content/full/2007/402/4

On the Way To Replacing the Brain
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If we are going to replace the brain for the long term, it will be slowly, neuron by neuron, with something more durable. The first, early steps on the path to the necessary technology are already underway, as reported in Popular Science: "The chip's ability to converse with live cells is a dramatic first step, he believes, toward an implantable machine that fluently speaks the language of the brain - a machine that could restore memories in people with brain damage or help them make new ones. Remedying Alzheimer's disease would, if Berger's grand vision plays out, be as simple as upgrading a bit of hardware. No more complicated drug regimens with their frustrating side effects. A surgeon simply implants a few computerized brain cells, and the problem is solved. ... I don't need a grand theory of the mind to fix what is essentially a signal-processing problem. A repairman doesn't need to understand music to fix your broken CD player. ... What the chip is saying is anyone's guess - the content of the conversation is beside the point ... It's straight mechanic-talk from the man who has created a prototype of the world's first memory implant, basically a hardware version of the brain cells in your hippocampus that are crucial to the formation of memory. The chip is meant to replace damaged neurons in the same way other prosthetic devices stand in for missing limbs or improve hearing."

Link: http://www.popsci.com/popsci/printerfriendly/science/0e54d952c97b1110vgnvcm1000004eecbccdrcrd.html

Sirtuins and Lamin A from Ouroboros
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I should point you to a pair of good posts from Chris Patil of Ouroboros, a blog that should be on your reading list if it is not so already.

Lamin A mutation and the cell cycle: A connection between progeria and normal aging:

Indeed, an extensive body of work over the past 5 years has clearly demonstrated that a particular mutation in the lamin A gene (LMNA) results in severe nuclear malformation. In humans, this mutation gives rise to a devastating disease, Hutchinson-Gilford progeria syndrome (HGPS).

...

Progerin [the mutated form of lamin A] is generated at some rate in normal cells (probably because the splice site ablated in the mutant is not 100% efficient), and when it accumulates to a detectable level, the same cell cycle interference and mitotic failures seen in HGPS can occur in an otherwise normal cell.

If the binucleated progeny of these cell divisions escape apoptosis, they will presumably undergo some type of permanent cell cycle arrest (e.g. senescence), and persist in the tissue - unable to divide further, but certainly available to cause damage to their microenvironment and contribute to age-related decline in tissue function.

Progeria now appears to be a grand exaggeration of a process that occurs at a low level in all our cells; learning to defeat progeria may just lead to a small portion of the medical technology needed for the defeat of all age-related degeneration. It continues to be the case that extreme examples of mutation or biochemical behaviors have a lot to teach us about the more normal workings of our cells and bodies.

Moving on:

Two on Sirtuin-2:

The sirtuins are a family of proteins named (somewhat unfortunately, in my opinion) after their founding and first-described member, the yeast histone deacetylase SIR2. In mammals, there are seven family members, SIRT1-7. Over the past few years, characterizing the function of each protein in every tissue it happens to be expressed has become something of a cottage industry: at the Cold Spring Harbor aging conference last fall, easily 25% of the talks were sirtuin-related.

...

This happens to be Sirt2’s week in the sun, with two independent studies revealing the protein’s role in regulating the cell cycle and differentation of the glial cells where it is expressed.

Modern biotechnology enables researchers to generate enormous amounts of data given starting points like sirtuins and a complex system like metabolism; the real challenge in the years ahead is the efficient synthesis of this data into new knowledge. For all the data collection, we don't yet have a clear understanding of how sirtuins fit into the way in which calorie restriction (or resveratrol, or other calorie restriction mimetics) produce beneficial effects on health and longevity.

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Pondering Pancreas Cell Regeneration
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From EurekAlert!, a good example of challenge, learning and progress in the field of regenerative medicine: "Replacing faulty or missing cells with new insulin-making cells has been the object of diabetes research for the last decade. Past studies in tissue culture have suggested that one type of pancreas cell could be coaxed to transform into insulin-producing islet cells. Now, [researchers] have demonstrated that these pancreatic acinar cells do not become insulin-producing cells in an animal model. However, they did show that injured pancreatic cells readily regenerate back into healthy acinar cells, which has implications for treating cancer and inflammation of the pancreas. ... Under certain conditions in tissue culture, acinar cells can synthesize insulin as well as amylase, a digestion enzyme. ... It is very clear that the acinar and islet compartments remain separate during regeneration in a live animal ... Although our work shows that acinar cells do not contribute to the insulin-producing compartment of the pancreas in an animal model, it is possible that other strategies might be successful in generating the islet cells. The hope is that these acinar cells would continue to make insulin after being transplanted back into the mouse."

Link: http://www.eurekalert.org/pub_releases/2007-04/uops-psp040307.php

The Latest Mprize Competitor Steps Forward
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The Methuselah Foundation announces the latest competitor for the Mprize: "The focus of Mr. Cash's research and development at Terra Biological LLC is on small molecules that simulate the genomic effects of caloric restriction ("caloric restriction mimics" or "CR mimetics"). CR mimetics have been shown to increase the lifespan of laboratory test animals, namely C. Elegans worms, D. Melanogater flies and, in a small pilot test, M. Musculus mice by up to 36%. ... The NIA/NIH is currently evaluating the inclusion of one of Terra Biological's CR mimetics in its ITP test program in mice to measure its biological effects on life and health span. These larger scale mouse tests will constitute the entry into the Mprize competition. ... My hopes in entering the Mprize competition are to demonstrate and confirm, on a larger scale in mice, the effectiveness of specific small molecule, biochemical control of aging. This biochemical control, which has already been shown to simulate calorie restriction - CR, a scientifically tested and accepted method of increasing life and health span - will be tested beginning with middle aged mice, about 16 months old."

Link: http://blog.methuselahfoundation.org/2007/04/methuselah_foundation_announce.html

Thoughts on Calorie Restriction Research
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Scientists are chewing over the past year of advances in calorie restriction and calorie restriction mimetic research, as indicated by a couple of recent papers on the subject.

Vertebrate aging research 2006:

The year's highlights include studies of oxidation damage in the very-long-lived naked mole-rat, and of caloric restriction in monkeys, humans, and growth hormone-unresponsive mice. Two studies of resveratrol, one showing its ability to extend lifespan in a short-lived fish, the other demonstrating beneficial effects in mice subjected to a diet high in fat, may well be harbingers of a parade of intervention studies in the coming decade.

Starving for Life: What Animal Studies Can and Cannot Tell Us about the Use of Caloric Restriction to Prolong Human Lifespan:

Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

"Starving" is over the top - even scientists are vulnerable to the urge for a better headline, it seems. Calorie restriction is anything but starvation, given the focus on optimal nutrition - and it's only infeasible if you're disinterested in looking after your health.

Still, some interesting points are raised, especially the idea that hunger might play a role in the regulatory mechanics that produce beneficial effects in our biochemistry. I can see that proposition spurring debate amongst the members of the Calorie Restriction Society, given the very different levels of self-reported hunger and various methodologies for managing it.

It's nice to see a researcher planting a flag in the map on the degree to which calorie restriction will extend human life span; all too few folk are willing to do that in public. It's interesting that those who do so tend to be the skeptics - not skeptical that it will work, but skeptical that calorie restriction will provide more than a couple of extra years of life in humans. Which is a couple of extra years of life on top of avoiding most of the common age-related illnesses, and generally being exceptionally healthy in old age, if the human studies continue to hold up.

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Heart Valve Grown From Stem Cells
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From the Guardian, another modest step towards bioengineered replacement hearts: "A British research team led by the world's leading heart surgeon has grown part of a human heart from stem cells for the first time. If animal trials scheduled for later this year prove successful, replacement tissue could be used in transplants for the hundreds of thousands of people suffering from heart disease within three years. ... By using chemical and physical nudges, the scientists first coaxed stem cells extracted from bone marrow to grow into heart valve cells. By placing these cells into scaffolds made of collagen, [scientists] then grew small 3cm-wide discs of heart valve tissue. Later this year, that tissue will be implanted into animals - probably sheep or pigs - and monitored to see how well it works as part of a circulatory system. ... Growing a suitably-sized piece of tissue from a patient's own stem cells would take around a month but he said that most people would not need such individualised treatment. A store of ready-grown tissue made from a wide variety of stem cells could provide good matches for the majority of the population."

Link: http://www.guardian.co.uk/medicine/story/0,,2048062,00.html

Let's Sequence the Exceptionally Long-Lived Mammals
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Via the Gerontology Research Group mailing list, my attention was drawn today to a proposal from biologist João Pedro de Magalhães and others to sequence the genomes of certain exceptionally long-lived mammals.

Proposal to Sequence Genomes of Unique Interest for Research on Aging

The proposal focuses on three organisms (in order of priority): the naked mole-rat (Heterocephalus glaber) whose record longevity of 28.3 years makes it the longest-lived rodent, the white-faced capuchin monkey (Cebus capucinus) which can live over 50 years, and the bowhead whale (Balaena mysticetus), the longest-lived mammal with an estimated longevity of over 200 years. If approved, these organisms will be added to the queue of target organisms to be sequenced, the sequencing will be carried out in one of the NHGRI-funded sequencing centers, and the entire genome sequences will be deposited in free public databases.

...

Aging is not only a major puzzle of biology but it has a profound impact on medicine with age-related diseases like heart diseases, type II diabetes, cancer, and neurodegenerative diseases among the leading causes of death in modern societies. Recent research has revealed several gene systems that can regulate longevity, aging, and multiple age-related diseases in short-lived model organisms. Nonetheless, the longevity effects of these genes are modest when compared to the lengthening of lifespans during evolution. Among mammals alone there is at least a 40-fold variation in maximum longevity. We still do not know why different species of similar body plan, biochemistry, and physiology can age at such different rates, but these differences must be seated in the genome.

In this white paper, we champion the idea that longevity should also be taken into consideration when choosing target organisms for sequencing, and we propose the sequencing of three organisms of unique interest for aging research (in order of priority) ... In particular Heterocephalus and Cebus have a much longer lifespan than expected for their body size.

The scientists backing the proposal are looking for letters of support from other engaged life scientists; give it some thought if you fit that description and are supportive of government-funded work on genome science.

As for myself, I am neither of these things, but the basic idea seems more interesting in many ways than the search for longevity genes in humans. I have mentioned whale longevity in the past; it is one good example of the way in which mammalian biochemistry could be reconfigured to be far more efficient than human biochemistry. Whales have many times as many cells as we do, and thus many times the risk of cancer, were they built the same way as humans - but they still make it through multiple centuries of life. For all that, the naked mole-rats are in many ways even more impressive, living more than eight times longer than similarly-sized peers in the animal kingdom.

A couple of other items of interest from the past on animal longevity:

I don't see the re-engineering of our biochemistry for longevity as a short-term proposition - it's a fearsomely complex undertaking. This sort of endeavor sounds like something we'll see much more of around the time that the first reseachers are designing entire human genomes with a good idea as to how to make things better. This will likely prove to be decades past the time at which we could have learned how to repair age-related damage in our present biochemistry. First things first, I say, for all that these prospects for the future are exciting ones.

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Calorie Restriction Late in Life
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How and why does calorie restriction provide health benefits if started late in life? EurekAlert! notes work on these and related questions: "Much research has shown that reduced calorie intake can increase health and longevity. Professor Stephen Spindler [and] his collaborators have discovered that reducing calorie intake later in life can still induce many of the health and longevity benefits of life-long calorie reduction. Importantly, this also includes anti-cancer effects. They are using this knowledge to establish a novel screening technique to find drugs which mimic this longevity effect. ... Physiological changes associated with ageing include cell damage and the emergence of cancer cells. The most important effects of low calorie diets and longevity therapeutics given late in life may not be to prevent this damage, but instead to stimulate the body to eliminate damaged cells that may become cancerous, and to stimulate repair in damaged cells like neurons and heart cells. Low calorie diets drive the body to replace and repair damaged cells. This process usually slows down as we age, but low calorie diets make the body re-synthesise and turn over more cells - a situation associated with youth and good health."

Link: http://www.eurekalert.org/pub_releases/2007-04/sfeb-int032907.php

Defending Human Enhancement
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Russel Blackford is commencing a discussion of the defense of human enhancement. "As a species, we have reached a point in our history where we've developed sophisticated, and increasingly powerful, forms of technological intervention in the functioning of our own bodies. ... Future technologies may go much further than anything available today in enabling transformation, and even the redesign, of human minds and bodies." Greatly extending the healthy human life span through forseeable medical technology is an enhancement. We shouldn't forget that all the froth and noise over preventing people from manipulating their own bodies and property very much boils down to "allowed to live or not." Which should hopefully trigger a response along the lines of "who are these damn fools telling me how and whether I can live or not? To hell with them!" So much of what passes for deep philosophical and ethical thinking these days is rendered obviously silly if you start from the premise that you own your body, and are free to do as you will with it provided you do not harm others, provided you take responsibility for the consequences of your actions, financial and otherwise.

Link: http://metamagician3000.blogspot.com/2007/04/prolegomema-to-defence-of-human.html

Commerce Drives Progress
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From FuturePundit, some thoughts on where you should be looking to see progress in implementing the next stages of regenerative medicine and enhancement built upon growing use of stem cells: "Professional athletes are not risk averse. The doping in baseball and by athletes in other sports demonstrates the huge health risks they'll run in order to win. Plus, they have big dollars to spend. Imagine that Michael Jordan could have gotten his knees fixed with stem cell therapies. He could have made millions more by playing more seasons. If athletes can find ways to take risks with stem cell therapies then stem cell therapies will advance more rapidly. I am also expecting plastic surgeons to embrace a lot of experimental stem cell therapies ahead of the mainstream medical community that treats diseases. The plastic surgeons mostly market to people who pay out of their own pockets. This gives them more flexibility. ... Once stem cell therapies for injury repair start happening then expect to see the therapies take off for rejuvenation. A bad joint from hard football tackles needs some of the same kinds of repairs as a bad joint from decades of wear and tear in the bodies of the elderly. ... Once a substantial market develops then part of the research to further improve treatments will get funded from cash flow."

Link: http://www.futurepundit.com/archives/004158.html

On Convincing People of the Merits of Healthy Life Extension
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A discussion is presently ongoing at the Immortality Institute, kicked off by thoughts on the frustrations and vicissitudes inherent in persuading people that healthy life extension to the degree of decades and centuries is plausible and desirable. Perhaps more importantly, that the process of developing the needed technology merits material support today.

Some time ago I decided to try and see how the concept of radical life extension would be accepted with some students from my university. So I introduced the idea to some of my acquaintances.

Well, I was faced with some religious arguments, which was to be expected, but the most overwhelmingly popular response was that of ridicule and unwillingness to accept that anything like this would EVER be possible.

I felt like everyone thought I was whacked in the head and there was no convincing that would help them believe that 20-30 years of life extension to reach the escape velocity would be possible.

Well, I said not to take my word for it and promised I would provide some material to prove that I am not completely gone crazy and some agreed (with a smirk). So I provided them with [biomedical gerontologist Aubrey de Grey's] presentation, [the Immortality Institute website], [the Exploring Life Extension film], Aubrey's site, [the Mprize for longevity research] and some others, all tied into a neat little package.

And the response to that: nothing, propably just assured them that I was insane. And the most obvious thing was that even though many of them weren't religious, it seemed that no-one cared. It was as if the whole matter couldn't be anymore insignificant.

We've all seen something of this response, I imagine. Just look at how long it takes any concept to overcome the resistance folk have to change; most people are slow to identify in public with any position not reinforced by their peers. It doesn't matter how obvious the new position is in hindsight, or how ridiculous and evil the present state of affairs is, the weight of opinions held by others is very important to most.

We are creatures built upon a foundation of ape instinct; normalization of expressed opinion and action within a hierarchy is second nature to us, and embracing the new on its merits as a leader, ahead of the curve, is not the human default. Facts are never as important as what others say about the conclusions supported by those facts - sad but true. Thus evangelizing the new takes time and effort. Yes, it is frustrating - but the frustration of the moment is really a matter of expectations. What are your expections with regard to the practical and possible rates of progress? What are your expections with regard to goals you might attain in the course of your activity?

That said, there is little worse than failing to try. The fellow quoted above made the effort - more effort than many do - to change the future for the better by bringing more people to think about living longer, healthier lives, and about the research that must be accomplished to make it happen. All of us can play a part in making support for healthy life extension research an accepted mindset. All it takes is the effort to talk to people about it; if we keep at it, if we persist, these ideas will gain the foothold needed to win out, blossom and spread on their merits in the mainstream of our culture.

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