Longevity Meme Newsletter, April 13 2009

April 13 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.



- SENS Foundation Launches
- Progress in SENS Research
- Excess Fat and Cognitive Decline
- Discussion
- Latest Healthy Life Extension Headlines


The big news of the last week is that the Methuselah Foundation has split into two: Strategies for Engineered Negligible Senescence (SENS) research will be managed by the new SENS Foundation, while the Methuselah Foundation now focuses on the Mprize for longevity science and new initiatives aimed at expanding the pro-longevity community:


"Back a few years, it seemed self-evident that the Mprize and SENS Research were synergistic programs for a single organization to operate, the growth of each boosting the other. Advocacy and encouragement for scientific research into extending healthy life on the one hand, and a specific research program aimed at doing just that on the other hand. That sounded sensible. It still sounds sensible. As it turned out, it didn't work that way in practice, however. The people and strategies best employed on the two sides of the house were different and really didn't operate in synergy. Instead of an engine, you have something more like a gentle tug of war on resources and goals. ... So now we'll see two organizations heading in the directions they feel most comfortable taking for success. There are signs that the Methuselah Foundation is looking to tap new communities for its pro-longevity advocacy, for example, aiming to grow the healthy life extension community via a more populist approach than was employed in the past."

If you are presently donating to the Methuselah Foundation in support of SENS research, your funds will be passed through to the SENS Foundation - you don't need to make any changes.


I should draw your attention to Aubrey de Grey's open letter on the launch of the SENS Foundation, in which he mentions some of the recent progress:


"I want to give you a feel for what we are achieving by summarising just two of the many recent elements of SENS-related scientific progress. One shining example is the discovery of enzymes that can destroy A2E, a by-product of the chemistry of sight, which is thought to be the primary cause of age-related macular degeneration (in turn, a major cause of blindness in the elderly). Kent Kemmish, a scientist working for the Methuselah Foundation's research group in Phoenix, leveraged knowledge built up in disparate fields over many years to have an inspired insight as to what type of enzyme might perform this task, and he was rapidly able to confirm this in the laboratory. The other example, this time relating to mitochondrial mutations (the strand of SENS that was my own first interest), is the breakthrough by Marisol Corral-Debrinski's Methuselah-funded group in Paris in cracking the problem of hydrophobicity of the proteins encoded by mitochondrial DNA. This obstacle, which had for over a decade completely stalled progress in the 20-year-old idea of making mitochondrial DNA redundant by duplicating it in the nucleus, is now largely solved, and there is great hope that this strand of SENS can be brought to complete fruition within only a few more years."

You can read more about these research programs, and how they apply to reversing the progression of aging, at the SENS Foundation site:



The evidence pointing to excess fat in early life as very damaging for your long-term health is weighty indeed - which likely means not just the fat, but the lack of exercise and diet required to attain it. Here's another study to add to all those that draw much the same conclusion:


"The participants completed baseline surveys in 1963 or 1973 (mean age 41.6 years, range 25-63 years). The surveys included questions about height, weight, diseases, and lifestyle factors. Beginning in 1986, the same individuals were assessed on neuropsychological tests every 3 years ... Persons with higher midlife BMI scores had significantly lower general cognitive ability and significantly steeper longitudinal decline than their thinner counterparts.

"Getting fat generally implies more eating and less exercise. In recent years, researchers have proposed a range of plausible biochemical mechanisms linking overeating, excess fat, and reduced exercise to a faster rate of progressive deterioration in the brain. The weight of scientific evidence tells us that if you're presently overweight and would like a better chance of living a longer, healthier life, then you should adopt a healthier lifestyle and diet that results in a lower stable weight and less visceral fat tissue."


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!




Steps Towards Reprogramming Cells For Regeneration (April 10 2009)
Researchers are working, step by step, towards the knowledge needed to reprogram cells to regenerate damage they presently let stand. Here is one small step forward: "A protein that the heart produces during its early development reactivates the embryonic coronary developmental program and initiates migration of heart cells and blood vessel growth after a heart attack ... The molecule, Thymosin beta-4 (TB4), is expressed by embryos during the heart's development and encourages migration of heart cells. ... Tremendous medical progress has been made to counter the damaging effects of heart attacks, but ordinarily, mammalian hearts are incapable of repairing themselves following damage. They are also limited in their ability to form new blood vessels. ... In this mouse study researchers found that TB4 initiates capillary tube formation of adult coronary endothelial cells in tissue culture. The molecule also encourages cardiac regeneration by inhibiting death in heart cells after an injury such as a heart attack and by stimulating new vessel growth. ... We observed that by injecting this protein systemically, there was increased cardiac function after a heart attack. We hope this protein can inhibit cell death that occurs during a heart attack in the short term, and that it may initiate new growth of coronary vessels by activating progenitor cells in the long term."

Stem Cells Versus Corneal Damage (April 10 2009)
From EurekAlert!: "Stem cells collected from human corneas restore transparency and don't trigger a rejection response when injected into eyes that are scarred and hazy ... The findings suggest that cell-based therapies might be an effective way to treat human corneal blindness and vision impairment due to the scarring that occurs after infection, trauma and other common eye problems ... corneal stem cells were able to remodel scar-like tissue back to normal. ... Our experiments indicate that after stem cell treatment, mouse eyes that initially had corneal defects looked no different than mouse eyes that had never been damaged ... The ability to grow millions of the cells in the lab could make it possible to create an off-the-shelf product, which would be especially useful in countries that have limited medical and surgical resources but a great burden of eye disease due to infections and trauma. ... The cornea and [its] stem cells themselves appear to be 'immune privileged,' meaning they don't trigger a significant immune response even when transplanted across species."

Common Sense, Health, and Longevity (April 09 2009)
The things that common sense tells us are good for long term health are in fact mostly good for long term health. Good diet and exercise will do more for you in the long term than any presently available therapy - which is all the more reason to get behind the wheel to push for the working medicines of rejuvenation that we know enough to create in the decades ahead. Here, Forbes looks at the basics: "Researchers at the University of Cambridge in England followed 20,000 middle-aged men and women in England for 11 years and found that nonsmokers with the healthiest eating and exercise habits at the outset had a 14-year-life-expectancy edge over the people with the worst habits. This followed a 2001 Loma Linda University finding that Seventh-Day Adventists who kept good habits lived to an average age of 88, versus 78 for those who behaved less well. ... Seventh-Day Adventists [have] a life expectancy four to seven years longer than that of average Americans, probably because their faith preaches a vegetarian diet and exercise. ... Researchers at the Pacific Health Research Institute in Hawaii who followed 5,820 Japanese American men for 40 years found those who avoided risk factors such as obesity, heavy drinking, smoking and high blood pressure in middle age had a 69% chance of living to be 85, versus just 22% for men with six or more risk factors."

Call For Submissions: Hourglass IX (April 09 2009)
Chris Patil is looking for your blog submissions for the next Hourglass blog carnival on aging science: "The ninth installation of Hourglass, a monthly blog carnival devoted to the best blogging about biology of aging, will appear at psique on Tuesday, April 14th. ... Topics of posts should have something to do with the biology of aging, broadly speaking - including fundamental research in biogerontology, age-related disease, ideas about life extension technologies, your personal experience with calorie restriction, maybe even something about the sociological implications of increased longevity. Opinions expressed are not necessarily those of the management, so feel free to subvert the dominant paradigm. If in doubt, submit anyway. Submissions should be emailed to [hourglass.host][at][gmail][dot][com]. ... By the way, if you'd like to volunteer to host, please email [Chris Patil] directly - basically the rest of 2009 is wide open. If you've already hosted before, don't let that hold you back; while the carnival is young, some repeat hosting is going to be par for the course."

CXCL5 and the Imflammation That Fat Tissue Generates (April 08 2009)
Researchers have been demonstrating over the past couple of years that excess fat tissue contributes to chronic inflammation, with the role of macrophage cells being particularly important. Here's more on that topic from EurekAlert!: "the inflammatory chemokine known as CXCL5 rises and falls with obesity and subsequent weight loss in humans. (Chemokines are structurally related signaling proteins that are secreted by cells.) ... Fat tissue known as white adipose tissue (WAT) is primarily involved in energy storage in the form of triglycerides and energy release in the form of free fatty acids, Fajas' team explained. However, WAT is more than a fat storage organ; it also secretes numerous other factors with roles in both health and disease. ... [CXCL5] is expressed at high levels in WAT, particularly in immune cells known as macrophages. Moreover, they report that CXCL5 is dramatically increased in the blood of people who are obese compared to those who are lean. Those CXCL5 levels drop when obese people lose weight and are also lower in obese individuals that continue to respond to insulin than in those who are insulin resistant. .... the [receptor for CXCL5] is active outside of muscle, in cells that line blood vessel walls and in the lung and intestine, for example. Therefore, increased CXCL5 circulating levels as observed in obesity could lead to other problems, including atherosclerosis and other inflammatory diseases."

How Overeating Leads to Insulin Resistance? (April 08 2009)
While some researchers are exploring the mechanisms by which calorie restriction brings health and longevity benefits, others are looking at how overeating harms us: "Obese people have been found to harbor proteins called branched-chain amino acids (BCAAs) at far higher levels than non-obese people. The suspicion has been that these amino acids, in combination with a high-fat diet, contribute to insulin resistance. ... In the case of the amino acids, we also are finding increased levels of their metabolic breakdown products, which suggests the whole system for handling the amino acid metabolic process has been overloaded. Our rat studies show that this overload causes changes at the cellular level that can lead to insulin resistance ... Insulin resistance occurred in animals with a diet high in the branched-chain amino acids, but only if they were ingested along with a high level of fat in the diet ... BCAAs comprise as much as 25 percent of amino acids in dietary protein, and are particularly enriched in diets high in animal (meat) proteins. ... I want to be clear that our animal data suggest that there is nothing wrong with obtaining protein from sources that are high in branched-chain amino acids, as long as you are not eating beyond what your energy needs are. If you add a lot of unneeded protein to a fatty diet, perhaps that's where you get into problems. The ancient Greeks were right: everything in moderation."

Where the Methuselah Foundation Goes From Here (April 07 2009)
An update from Methuselah Foundation CEO Dave Gobel: "The restructuring of Methuselah Foundation allows us to be more nimble as we grow, and enables us to incubate and launch a variety of programs. I'm writing you today to share with you our short, medium and long-term strategies that advance our core mission of ending age-related diseases through awareness, education, scientific research, and direct community outreach. ... As you know, it is has been a challenge to communicate our message to the mainstream public. It is our belief that providing instant real world updates to those with life threatening diseases, and their support networks, will introduce a significantly larger audience to our overall mission while providing a beneficial program for people in need. ... The core focus in our fight to end age related diseases is found in the MPrize, a breakthrough approach to giving cutting-edge science the resources needed to solve one of the largest humanitarian crises of our time. The MPrize springs from a simple truth: the greatest innovations in human history have always been fueled by three things... competition, imagination and the entrepreneurial spirit. Science is no different. ... We remain firmly committed to continuing support for groundbreaking rejuvenative research, taking further strides in our global mission to develop, promote, and provide widespread access to regenerative medicine solutions and therapies to end the disabilities and diseases of aging. We have many exciting new breakthrough rejuvenation projects in the works, which we will be announcing in the very near future."

SENS Foundation Launches (April 07 2009)
Strategies for Engineered Negligible Senescence (SENS) research will be conducted by the SENS Foundation going forward. This initiative is spun off from the Methuselah Foundation, which will renew its focus on the Mprize for longevity science and a number of other less research-focused endeavors. From biomedical gerontologist and SENS Foundation co-founder Aubrey de Grey: "I want to give you a feel for what we are achieving by summarising just two of the many recent elements of SENS-related scientific progress. One shining example is the discovery of enzymes that can destroy A2E, a by-product of the chemistry of sight, which is thought to be the primary cause of age-related macular degeneration (in turn, a major cause of blindness in the elderly). ... The other example, this time relating to mitochondrial mutations, [is] the breakthrough by Marisol Corral-Debrinski's Methuselah-funded group in Paris in cracking the problem of hydrophobicity of the proteins encoded by mitochondrial DNA. This obstacle, which had for over a decade completely stalled progress in the 20-year-old idea of making mitochondrial DNA redundant by duplicating it in the nucleus, is now largely solved, and there is great hope that this strand of SENS can be brought to complete fruition within only a few more years. I have no doubt that SENS Foundation is the right organization to take the next evolutionary steps in the engineering of comprehensive regenerative therapies. ... It promises to be a remarkable journey, and I look forward to your continued interest, support and collaboration as we increase our pace and set our sights ever closer to the horizon."

Building Tissue From Embryonic Stem Cells (April 06 2009)
A proof of concept for the use of pluripotent cells in tissue engineering from ScienceDaily: scientists "report on their research to optimize the potential of [human embryonic stem cells or hESC cells] to generate complex, functional multilayer tissues, such as the oral mucosa and skin, and to understand how tissue fabrication is controlled and directed. ... [Researchers] used tissue engineering principles to produce complex oral-lining tissues that mimic many features of their counterparts found in the oral cavity. Making these tissues was a two-step process. With a combination of chemical signals and specialized surfaces on which these cells attach, an hESC cell line [was] directed toward two divergent cell populations. The first population comprises the surface layer (epithelial cells) of complex tissues, while the other is found beneath these cells (mesenchymal cells). ... The populations were then grown at an air-liquid interface to mimic their growth environment in the oral cavity. Within two weeks, tissues developed that shared many features in common with normal tissues that were constructed with mature cells that are the 'gold standard' of normal tissue generation in our lab."

Stem Cells That Grow New Blood Vessels (April 06 2009)
Via EurekAlert!, we learn that a research group has "has identified how to use selected stem cells from bone marrow to grow new blood vessels to treat diseases such as peripheral artery disease. ... [Researchers] drew human bone marrow and simultaneously isolated three different types of stem cells that co-ordinate together to form new blood vessels. These are called pro-angiogenic stem cells. They were purified to remove any inflammatory or contaminated cells, and then injected into the circulation of mice which had one of their leg arteries ligated and removed. The researchers showed how these stem cells have a natural ability to hone in on the area of ischemia to induce blood vessel repair and improve blood flow ... We can select the right stem cells from the patient's own bone marrow and put them back in the area of ischemia to allow these cells to coordinate the formation of new blood vessels. These principles could be applied not only to ischemic limbs, but to aid in the formation of new blood vessels in ischemic tissue anywhere in the body, for example after a stroke or heart attack."



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