Longevity Meme Newsletter, September 03 2007
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September 03 2007

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.



- Researchers on Longevity Science
- SENS 3 Starts on September 6th
- Discussion
- Latest Healthy Life Extension Headlines


Researchers on the Gerontology Research Group mailing lists have been debating the nature and organization of longevity science over the past week. You'll find views from Robert Bradbury and Derya Unutmaz reproduced at Fight Aging!:


"It should be realized that for a number of reasons one can view 'aging research' as a situation similar to that of the 1986 movie with Tom Hanks and Shelly Long, 'The Money Pit.' ... It is useful to keep in mind that Larry Ellison, through the Ellison Medical Foundation, has probably personally dumped between $100 and $200 million into aging research and it could easily be argued that there is little to show for it. One of the key reasons for that, IMO, is that the money was spent within a 'research' framework rather than a business (solution) framework."


"I fully agree that there is no biological reason why human life can not be extended indefinitely and at some point in future (hopefully near one) in my opinion it is almost a certainty this will be achieved. The point that I disagree with (if I understood correctly) is that the current biological research somehow can be directed, made less wasteful and if the money were to be spent 'wisely' we can then achieve the above goal much quicker. Research by its nature, especially in biological sciences because of enormous complexity, is very wasteful. This is simply because we have not yet identified all the components of the system we are studying, let alone have the capability to put it together from it's individual pieces."

From where I stand, it seems to me that research is no more inherently risky or complex than starting a company - the same risk management and investment strategies can be applied. What most large funding organizations (especially arms of government like the NIH) are lacking are accountability for results, explicit goals and timelines. In the absence of strong incentives for success and consequences for failure, there will always be massive waste of resources and slower progress - ergo matters can indeed be made to move much more rapidly than at present:



The third Strategies for Engineered Negligible Senescence conference kicks off on the 6th in Cambridge, UK:


"The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Methuselah Mouse Prize), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair -- reverse -- those changes, rather than merely to slow down their further accumulation."

The program and list of accepted abstracts show the breadth of biomedicine relevant to the repair of age-related cellular and molecular damage:


A number of Immortality Institute folk and Methuselah Foundation volunteers are planning a pre-conference meeting on the 5th:


Also worth noting: members and valued donors of the Foundation's Three Hundred will be meeting for dinner that evening:



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!




To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

A Glance at AGE-Breaker Research (August 31 2007)
Given the role played by advanced glycation end-products (AGEs) in aging, scientists continue to search for ways to destroy or limit the accumulation of these compounds. Regulation generally forces such studies to relate to the treatment of age-related diabetes - intervention in aging is not recognized as a legitimate field of research by the FDA, so therapies will not be approved for use, and thus funding cannot be found for development. "We investigated the effects of various concentrations of a compound, LR-90, on the progression of renal disease and its effects on AGE and receptor for AGE (RAGE) protein expression on the kidneys of [diabetic rats] ... LR-90 treatment [reduced] kidney AGE/ALE accumulation and RAGE protein expression ... In vitro, LR-90 exhibited general antioxidant properties ... The compound also prevents AGE-protein cross-linking reactions. These findings demonstrate the bioefficacy of LR-90 in treating [diabetic animals] by inhibiting AGE accumulation, RAGE protein expression, and protein oxidation in the diabetic kidney. Additionally, our study suggests that LR-90 may be useful also to delay the onset and progression of diabetic atherosclerosis." All of which would be beneficial as applied to normal aging - assuming that this compound is useful in people. Most prospective AGE-breakers coming from animal studies fail to do much good in humans, as the mix of AGE compounds is quite different.

Life Extension by Calorie Restriction in Humans (August 31 2007)
More scientists are weighing in with estimates of the effects of calorie restriction (CR) on humans - estimate being the key word: "in humans there are no life-long studies of CR, only short term trials which indicate that 20% CR acting over periods of 2 to 6 years is associated with reduced body weight, blood pressure, blood cholesterol and blood glucose, risk factors for the major killer diseases of cardiovascular disease and diabetes. In addition recent research has shown that CR acting for 6 months is able to improve biomarkers for longevity (deep body temperature and plasma insulin) and thus should increase life expectancy. The magnitude of the life extension effect of CR in humans can only be estimated. The Okinawans, the longest lived people on earth, consume 40% fewer calories than the Americans and live only 4 years longer. Similarly, women in United States consume 25% fewer calories than men and live 5 years longer. From the survival studies of overweight and obese people it is estimated that long-term CR to prevent excessive weight gain could add only 3 to 13 years to life expectancy. Thus the effects of CR on human life extension are probably much smaller than those achieved by medical and public health interventions, which have extended life by about 30 years in developed countries in the 20th century." The health benefits are still inarguably good, of course.

Blowing Up the Immortal Strand Hypothesis (August 30 2007)
From PhysOrg.com: "How do adult stem cells protect themselves from accumulating genetic mutations that can lead to cancer? For more than three decades, many scientists have argued that the 'immortal strand hypothesis' - which states that adult stem cells segregate their DNA in a non-random manner during cell division -- explains it. ... [researchers] labeled DNA in blood-forming mouse stem cells and painstakingly tracked its movement through a series of cell divisions. In the end, they found no evidence that the cells use the immortal-strand mechanism to minimize potentially harmful genetic mutations. ... This immortal strand idea has been floating around for a long time without being tested in stem cells that could be definitively identified. This paper demonstrates that it is not a general property of all stem cells." The more we know about the changes that accumulate in cells with age - and the mechanisms by which those changes occur - the better armed we are work towards the repair of aging.

A Future of Molecular Manufacturing (August 30 2007)
An article by Chris Phoenix of the Center for Responsible Nanotechnology can be found at Nanotechnology Now. Molecular manufacturing (MM) will bring a new industrial revolution, in effect, and one of the areas to benefit greatly will be medicine: "Although the human body and brain are awesomely complex, MM will lead to rapid improvement in the treatment of many diseases, and before long will be able to treat almost every disease, including most or all causes of aging. The first aspect of medicine to benefit may be minimally invasive tests. ... Even with a conservative approach, inexpensive continuous screening for a thousand different biochemicals could give doctors early indications of disease. (Although early MM may not be able to build a wide range of chemicals, it will be able to build detectors for many of them.) Such monitoring also could reduce the consequences of diseases inadvertently caused by medical treatment by catching the problem earlier. ... Today, in advanced arthroscopic surgery, simple surgical tools are inserted through holes the size of a finger; a nano-built surgical robot with far more functionality could be built into a device the width of an acupuncture needle."

Molecular Basis of Aging, Conference Review (August 29 2007)
Chris Patil was kind enough to post on his review of a recent conference on aging science, including the full PDF version: "Nearly 20 years ago, researchers discovered that lifespan can be extended by single-gene mutations in the nematode worm Caenorhabditis elegans. Further studies revealed that the mechanisms governing aging in the smallest organisms have been evolutionarily conserved and may operate in human beings. Since then, the field of biogerontology has expanded considerably, learning from - and contributing to - such disparate fields as cell signaling, metabolism, endocrinology, and a wide range of human diseases including cancer. To date, newly discovered connections and novel interdisciplinary approaches gradually unify what once seemed unrelated observations between seemingly disparate research areas. While this unification is far from complete, several overlapping themes have clearly emerged. At the 95th International Titisee Conference, devoted to 'The Molecular Basis of Aging,' 60 of the world's pre-eminent biogerontologists shared their most recent findings in the biology of aging, and discussed interdisciplinary connections between diverse fields."

Progress in Gene Therapy Versus Alzheimer's (August 29 2007)
Researchers continue to make solid progress in the development of gene therapies to clear out aggregations of unwanted compounds in our bodies: "Alzheimer's involves a protein called amyloid-beta, which makes up gooey clots or plaques that form in the brain. These toxic clumps, along with accessory tangled fibers, kill brain cells and interfere with memory and thinking. The situation has been compared to a build-up of cholesterol in coronary arteries. ... Delivery of genes that led to production of an enzyme that breaks up amyloid showed robust clearance of plaques in the brains of the mice ... The gene delivery technique employed by the research team has been used in several other trials with animals that model human diseases, including cancers. The procedure involves removing cells from patients, making genetic changes, and then putting back the modified cells, which should treat a disease or disability. So far, this approach has produced encouraging results for cancers, blood, muscle, and eye diseases, spinal cord injuries, stroke, Parkinson's and Huntington diseases, and amyotrophic lateral sclerosis."

Another View of Alzheimer's Research (August 28 2007)
The amyloid and tau focus of Alzheimer's research is not universal in the scientific community. From the NYAS: "the well-characterized buildup of amyloid plaques and tangles of tau are not the only biochemical phenomena wrought by this neurodegenerative disease. And this line of investigation, while able to clarify many of the mechanisms that lead to the pathological activity of these proteins, has yet to produce a new drug that successfully treats the disease. ... Aaron Chuang of GlaxoSmithKline characterized this intellectual history of [Alzheimer's disease (AD)] research by referring to a proverb: A frog that grows up in the bottom of a well believes the little sliver of sky he sees is the whole world. Along these lines, the little that we've known about AD until recently has limited the questions that we've asked. While [amyloid beta] and tau are certainly important in the disease, the etiology and mechanisms of AD are probably much broader. Other approaches to thinking about the disease may be essential to unearth new insights and strategies for drug therapies."

Myostatin, Follistatin and Mightier Mice (August 28 2007)
You might recall manipulation of myostatin touted as a potential therapy for age-related muscle decline and wasting diseases. EurekAlert! notes that the basic science has already been improved: "mice that lack the gene that makes myostatin have roughly twice the amount of body muscle as normal, mice without myostatin that also overproduce follistatin have about four times as much muscle as normal mice. ... follistatin was capable of blocking myostatin activity in muscle cells grown under lab conditions. When he gave it to normal mice, the rodents bulked up, just as would happen if the myostatin gene in these animals was turned off. He then genetically engineered a mouse that both lacked myostatin and made extra follistatin.... To my surprise and delight, there was an additive effect ... these muscular mice averaged a 117 percent increase in muscle fiber size and a 73 percent increase in total muscle fibers compared to normal mice. These findings show that the capacity for increasing muscle growth by targeting these pathways is much more extensive than we have appreciated."

Engineering Heart Regeneration (August 27 2007)
Tissue engineering and regenerative medicine are starting to see a synthesis of the variety of techniques prototyped in past years. Here's a good example of the type via ScienceDaily, using many of the methods so far developed: "When human heart muscle cells derived from embryonic stem cells are implanted into a rat after a heart attack, they can help rebuild the animal's heart muscle and improve function of the organ ... researchers had struggled to get stem cells to differentiate into just cardiomyocytes, or heart muscle cells - most previous efforts resulted in cell preparations in which only a fraction of 1 percent of the differentiated cells were cardiac muscle cells. By treating the stem cells with two growth factors, or growth-encouraging proteins, and then purifying the cells, they were able to turn about 90 percent of stem cells into cardiomyocytes. The researchers dealt with the other big challenge of stem cell death by implanting the cells along with a cocktail of compounds aimed at helping them grow. The cocktail included a growth 'matrix' - a sort of scaffolding for the cells to latch on to as they grow - and drugs that block processes related to cell death. ... 100 percent of rat hearts showed successful tissue grafts."

SENS 3 Starts Soon: September 6th (August 27 2007)
Researcher Attila Chordash reminds us that the third Strategies for Engineered Negligible Senescence conference starts on September 6th: "The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Methuselah Mouse Prize), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem ... SENS3 is not an average conference in any respect and I am really happy to [participate], firstly, as this was the only conference I found where there are both good mitochondrial and stem cell biology sessions and those are my 2 major biological topics. [Secondly] there will be a lot of biogerontology presentations on aging. [Thirdly] because this is the only scientific conference that includes the heavyweight life extension supporter scholar fellows, including the organizer Aubrey de Grey or the practical life extensionist Ray Kurzweil."


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