Longevity Meme Newsletter, August 24 2009

August 24 2009

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.



- Laser Ablation Fundraising Successful
- The A4M Version of the Longevity Dividend
- An Update on AGE-Breaker Research
- Discussion
- Latest Healthy Life Extension Headlines


I'm pleased to report success for the Immortality Institute's most recent grassroots fundraising initiative was a success. The funds - more than $16,000 once all the matching is completed - will go to a project intended to validate the use of lasers to break down damaging accumulation of lipofuscin in aged cells:


"Congratulations are due to the volunteers and advocates who managed the fundraising efforts. This sort of thing is a great model for the future of biotechnology, in which important proof of concept research becomes so cheap - indeed, has already become so cheap - that it can be funded in this manner.

"It will take a couple days to get the exact accounting of the amount donated. Then Imminst will cut a check to [the SENS Foundation, who will be managing the actual research project]. Nason [Schooler] has already begun preparations for full blown experiments and expects to keep us up to date when things start in earnest. So things are already set-up and should get going in about a week or two."

Many thanks to those newsletter readers who chipped in to help make this a success. This is era in which important work in biotechnology can get underway with comparatively little money, and here we are demonstrating just that.


One of the larger and more influential organizations in the "anti-aging" marketplace recently put forward what is in effect their own version of the Longevity Dividend proposal. I see this as an interesting sign of the times:


"Now regardless of your thoughts on the content or the nature of the messenger - and as for many of these things there's some sanity and good sense mixed in there if you want to dive in and look for it - this seems very much to me like a vote of confidence in the Longevity Dividend. The folk at A4M believe that the Longevity Dividend - or something very much like it - will succeed in redirecting a significant amount of government funding towards applied aging research. You'll recall that the Longevity Dividend itself is essentially a proposal for how to spend public funds on medical research and development to slow the aging process. Spending without end, limit, or sense of consequence is in the air, it seems, and groups are looking at how best to position themselves before the trough in their particular neck of the woods is filled.

"Given the zeitgeist, more public funding for anything and everything that has political pull seems likely. It will be interesting to see - in that watching an avalanche roaring down the slope towards you sort of way - exactly how these particular tumbling rocks fall. Are these unfolding political efforts a fair proxy for the evolving opinions of the masses in regard to longevity science or not? If they are, then we may see a promising evolution of distributed efforts in aging-related biotechnology development in the years ahead as costs fall - distributed efforts that should be somewhat protected from whatever economic disasters are being set up by present policies."


Advanced glycation endproducts (AGEs) are another form of unwanted biochemical that are both ingested in the diet and generated by the body's own metabolic processes. Some are short-lived but nonetheless grow in number as the body ages, whilst others are very long-lived and accumulate because the body cannot break them down. One long-running - but unfortunately not very popular - line of longevity research is the development of AGE-breakers, drugs that can safely remove the types of AGE important in humans and thereby reverse this aspect of the aging body.

Here, I look at Torrent Pharmaceuticals, one of the few groups presently working in this field, and their drug candidate TRC4186:


"Most commercial AGE-breaker research focuses on diabetes because regulatory bodies such as the FDA do not recognize aging or 'normal' AGE accumulation as diseases, and won't approve any medical application of therapies to that end. Thus researchers are forced into channeling research towards officially approved and defined diseases that happen to include some of the same issues in their pathology. Diabetes is the best option for commercial application of AGE-breakers under these imposed limits because of its biochemistry and the fact that it is widespread in this age of too much food and not enough exercise.

"Without meaning to denigrate the hard work of the researchers here, TRC4186 isn't all that exciting based on [this latest animal study in rats]. In fact, this looks very much like a repeat of ALT-711 or alagebrium, an early AGE-breaker compound - predating modern designer drug methodologies enabled by new biotechnology - that performed well in rats but terribly in humans. As it turns out, the difference in rat versus human life span leads to very different types of AGEs being important. The lesson learned there is that animal studies of AGE-breakers are in no way a convincing demonstration of their utility, as is unfortunately sometimes the case in new medical technology."


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




Here is something for those of you who will be in the New York area this time next month: "The Singularity Institute for Artificial Intelligence is co-sponsoring a program on ending aging with gerontology researcher Aubrey de Grey and the New York Academy of Sciences, on the evening of Tuesday, September 22nd in New York City. ... Could it be possible for humans to live hundreds of years in the very near future? Is aging a curable disease? Iconoclast Aubrey de Grey predicts it's only a matter of decades before regenerative medicine extends human life expectancy indefinitely. This event is one of five events in the 2009 Provocative Thinkers Series presented by Science & the City, a program of the New York Academy of Sciences. Cosponsored by the Singularity Institute." A large number of de Grey's past presentations to groups large and small can be found at YouTube - you might want to take a look.

A dialysis machine, intended to replace the function of damaged kidneys, might weigh 55kg. Researchers now have that down to 5kg in a wearable form, a machine which does a better job to boot. Looking ahead, we'd expect even more effective implants or bracelets worn over surface veins in the 2020s - essentially viable artificial replacements for the function of an organ. This is an important trend to watch, as I believe it will ultimately contribute to enhanced longevity just as greatly as regenerative medicine: "Our vision of a technological breakthrough has materialized in the form of a Wearable Artificial Kidney, which provides continuous dialysis 24 hours a day, seven days a week ... The device - essentially a miniaturized dialysis machine, worn as a belt - weighs about 10 pounds and is powered by two nine-volt batteries. Because patients don't need to be hooked up to a full-size dialysis machine, they are free to walk, work, or sleep while undergoing continuous, gentle dialysis that more closely approximates normal kidney function. ... We believe that the Wearable Artificial Kidney will not only reduce the mortality and misery of dialysis patients, but will also result in significant reduction in the cost of providing viable health care."

Mitochondrially-targeted antioxidants - such as catalase - have been shown to extend life span in mice. Here is a method of using catalase that employs a viral vector: "Earlier studies have found that mice would live longer when their genome was altered to carry a gene known as mitochondria-targeted catalase gene, or MCAT. However, such approaches would not be applicable to human. Duan and Dejia Li [took] a different approach and placed the MCAT gene inside a benign virus and injected the virus into the mice. Once injected, Duan and Li tested the mice and found that they could run farther, faster and longer than mice of the same age and sex. Duan attributes this performance enhancement to the MCAT and believes the gene is responsible for removing toxic substances, known as free radicals, from the mitochondria, the powerhouse of the cell. By using this specific gene therapy vector, the virus, to introduce the longevity gene, Duan and Li opened the possibility of human treatment. ... Our results suggest similar therapy may one day improve the life quality of the elderly. This could have important implications for many diseases, such as muscular dystrophy, heart disease, diabetes and neurodegenerative diseases. These patients typically have too many toxic free radicals in their cells."

LIKE CLOCKWORK (August 20 2009)
Mainstream press articles on increasing life expectancy arrive on a schedule like clockwork: "U.S. life expectancy has risen to a new high, now standing at nearly 78 years ... The increase is due mainly to falling death rates in almost all the leading causes of death. The average life expectancy for babies born in 2007 is nearly three months greater than for children born in 2006. ... Life expectancy is the period a child born in 2007 is expected to live, assuming mortality trends stay constant. U.S. life expectancy has grown nearly one and a half years in the past decade, and is now at an all-time-high. ... Japan has the longest life expectancy - 83 years for children born in 2007, according to the World Health Organization. The CDC report found that the number of deaths and the overall death rate dropped from 2006 - to about 760 deaths per 100,000 people from about 776. The death rate has been falling for eight straight years, and is half of what it was 60 years ago. Heart disease and cancer together are the cause of nearly half of U.S. fatalities. The death rate from heart disease dropped nearly 5 percent in 2007, and the cancer death rate fell nearly 2 percent, according to the report." Life expectancy is a statistical construct that looks back into the past to measure trends; it doesn't actually have anything to say about how long people born today are likely to live. This, after all, is an era of great change and progress in biotechnology.

From Accelerating Future, thoughts on goals: "Superlongevity, superintelligence, and superabundance are a perfect summary of what we want and need. How can we achieve them? Superlongevity can be achieved by uncovering the underlying mechanisms of aging and counteracting them at the molecular level faster than they can cause damage. Huge research project, a long-term effort, but definitely worth the time and money. Leading organization in this area? The SENS Foundation. Superintelligence will be a difficult challenge, creating an intelligent being smarter than humans in every domain. It could take decades, or possibly longer, but it does seem possible. ... Superabundance can be achieved by creating programmable self-replicating machines powered and supplied by easily available resources and materials ... Achieving superlongevity, superintelligence, and superabundance will be incredibly challenging, but seemingly inevitable as long as civilization continues to progress ... There is no guarantee that we will achieve these goals in our lifetime - but why not try? Achieving any of these milestones would radically improve quality of life for everyone on Earth. The first step to making technological advancements available to everyone is to make them available for someone."

Researchers are looking for ways to apply knowledge of the longevity gene klotho for medical benefit: "A newly-discovered anti-aging gene could be manipulated to stop or even prevent high blood pressure, a leading contributor to early death ... Persistent high blood pressure, also called hypertension, can lead to stroke, heart attacks and kidney failure. About one-third of Americans struggle with the condition ... an anti-aging gene called klotho decreases as humans age while hypertension tends to increase. Increasing the expression or output of the gene in lab animals reduced blood pressure and reversed kidney damage from hypertension. Sun said testing on humans is the next step, and it would be years before a therapy could be sold. ... All of us will be and should be extremely hopeful this can occur. ... it's possible the therapy could protect other organs - such as the brain and eyes - from conditions related to aging." This is all pretty speculative beyond the fact of the animal study results - and for most people lifestyle conditions like hypertension are very avoidable. Lead a fat, sedentary life, and don't be surprised when your body starts to fail more rapidly than those who kept fit or practiced calorie restriction.

Scientists continue to experiment successfully with the use of stem cells to engineer regeneration: "researchers have identified stem cells that are able to grow new coronary arteries, a finding that could lead to new ways to treat atherosclerosis. ... We have defined this novel class of primitive cells and named them coronary vascular progenitor cells [CVPCs]. These cells possess all of the fundamental properties of stem cells and are distributed within niches located in the vessel wall of the entire human coronary circulation system. ... To test the activity of these cells, the scientists created a blockage in a coronary artery in dogs and injected human CVPCs in the blocked artery. After one month, the dogs showed improvements in blood flow and heart functioning. The researchers found that the dogs had grown large, intermediate and small human coronary arteries. ... The findings suggest that the human heart contains a reservoir of CVPCs that can be used to create a biological bypass in patients with chronic coronary artery disease and ischemic cardiomyopathy, which results when arteries that supply blood and oxygen to the heart are blocked."

To the man in the street and mainstream journalism, medical science is nothing more than drug development - an unfortunate and blinkered viewpoint. Here is that viewpoint turned to regard research into metabolic manipulation to slow aging: "It may be the ultimate free lunch - how to reap all the advantages of a calorically restricted diet, including freedom from disease and an extended healthy life span, without eating one fewer calorie. Just take a drug that tricks the body into thinking it's on such a diet. It sounds too good to be true, and maybe it is. Yet such drugs are now in clinical trials. Even if they should fail, as most candidate drugs do, their development represents a new optimism among research biologists that aging is not immutable, that the body has resources that can be mobilized into resisting disease and averting the adversities of old age. This optimism, however, is not fully shared. Evolutionary biologists, the experts on the theory of aging, have strong reasons to suppose that human life span cannot be altered in any quick and easy way. But they have been confounded by experiments with small laboratory animals, like roundworms, fruit flies and mice. In all these species, the change of single genes has brought noticeable increases in life span."

Here's video of a recent presentation by biomedical gerontologist and longevity science advocate Aubrey de Grey: "Dr Aubrey de Grey, author of the book 'Ending Ageing', explains in a clear, concise way in which it may be possible to add years onto the average life expectancy of a human being. Biological ageing is a progressive, degenerative process of decay. As ageing damage accumulates in our functional cellular and molecular structures, the healthy order laid down in our youth slowly falls apart. This damage occurs, as a result, of a series of unintended biochemical side effects of normal metabolism. As more and more of our cellular and molecular structures suffer this damage, functionality is lost, and health, resilience and vitality are slowly taken away from us, leading to increasing age-related pathology. Thus, metabolism causes ongoing ageing damage; this eventually accumulates to reach a critical mass at which it causes age-related frailty, disability, disease, and ultimately death. Aubrey looks at what approaches are already being taken e.g. in the areas of Geriatrics and Gerontology and introduces a third theoretical approach: SENS, which targets the damage of ageing itself, bringing it down to levels below the threshold at which it causes problems."

I notice that Genescient's newly relaunched website is up and running, and provides much more information as to what the company is up to: "Our focus is to extend healthy human lifespan by using advanced genomics to develop therapeutic substances that attack the diseases of aging. We are the first company founded to exploit artificial selection of animal models for longevity. Our extremely long-lived animal models (Drosophila melanogaster) have been developed over 700 generations. They are an ideal system for the study of aging and age-related disease because Drosophila metabolic genetic pathways that are highly conserved in humans. Our sophisticated analysis cross-links gene function in Drosophila with their human orthologs, thus revealing the targets for therapeutic substance development. To date we have discovered over 100 of these genomic targets, all related to the primary diseases of aging. This large library of targets, enables Genescient to effectively select and test therapeutic drug candidates. To date, Genescient's 'proof-of-concept' testing program has yielded a number of very promising therapeutic substances."



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