Longevity Meme Newsletter, January 25 2010

January 25 2010

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.



- A Look at Calorie Restriction Mimetic Research
- Reports From a Youthful Cryonics Meeting
- Thoughts on Scientific Consensus
- Discussion
- Latest Healthy Life Extension Headlines


These days much of the investment into research aimed at slowing aging goes towards investigation and development of calorie restriction mimetics. These are drugs intended to replicate (or, ambitiously, improve upon) one or more of the beneficial changes in metabolism brought about through calorie restriction in mammals. These changes lead to greatly improved health and enhanced longevity in almost every species tested to date. Here is a small selection of recent research in the field:


"One of the more interesting frontiers in research aimed at slowing aging is the search for methods that complement calorie restriction rather simply recapturing a part of its benefits to health and longevity. To date, there have not been much in the way of results on this count, but I think that this will change: the number of ways to extend life in laboratory animals is expanding rapidly, as is the pool of funding for the field. ... Based on the behavior of rapamycin and calorie restriction tested separately in flies and mice, it would be consistent for rapamycin to further extend the life span of calorie restricted mice - and hence other mammals too. Which in turn means [that] there exist other accessible mechanisms of metabolic determination of longevity that are not triggered by calorie restriction."


"Both calorie restriction and exercise share some mechanisms in common, such as improving the operation of heat shock proteins ... Heat shock proteins are one aspect of the process of autophagy, wherein damaged materials and cellular components are recycled. Calorie restriction may operate largely through boosting autophagy ... If being charitable, we might think of any drug that boosts autophagy, the operation of heat shock proteins, or one of the other biochemical changes brought on by calorie restriction as a form of calorie restriction mimetic. ... Drugs engineered to boost or repair failing autophagic processes in the old are, to my eyes, the most promising potential outcome of this wide-ranging field of research. Improved autophagy in the old can clear out intracellular aggregates and the buildup of cellular damage, which is exactly a form of rejuvenation - restoring an aspect of the aging cellular environment to youthful levels. Therapies built upon such drugs would be limited to reversing only those forms of age-related damage that autophagy can clean up, but it is nonetheless a form of rejuvenation."


For the cryonics community to continue to move ahead, it must grow:


"Cryonics is the science and business of the low-temperature preservation of the body and brain upon clinical death. By preserving the fine structure of the brain, you preserve the data stored within - the mind itself. Cryopreserved individuals can then wait for as long as needed for technologies to advance to the point at which they can be restored to active life. Typically, this is envisaged to involve molecular manufacturing and medical nanorobots capable of cellular repair - none of which is impossible under our present understanding of the laws of physics.

"But the vitrified waiting part of the equation requires the cryonics community to continue and expand from generation to generation. From this community are drawn the (presently few) professionals in the cryonics field, financial support for operations, and other necessities for running a cryonics provider as a long-term business. Those older folk who presently support cryonics expect to be cryopreserved, and their legacy protected by younger supporters - which means that all the normal advocacy and community engineering undertaken in any successful field of human endeavor are especially important here. This noted, I see there are two reports published online in recent days from members of the community who attended a meeting of younger cryonics supporters and advocates, held earlier this month in Florida."


Science in practice is anything but neat and tidy, and reading the output of the scientific community is a skill that must be learned and practiced, just like any other:


"The scientific community doesn't produce an output of nice, neat tablets of truth, pronouncements come down from the mountain, however. It produces theories that are then backed by varying weights of evidence: a theory with a lot of support stands until deposed by new results. But it's not that neat in practice either. The array of theories presently in the making is a vastly complex and shifting edifice of debate, contradictory research results, and opinion. You might compare the output of the scientific community in this sense with the output of a financial market: a staggeringly varied torrent of data that is confusing and overwhelming to the layperson, but which - when considered in aggregate - more clearly shows the way to someone who has learned to read the ticker tape."


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!




Stroke is another cause of death wherein risk is significantly increased by obesity: "Analyzing the ARIC Study database in which subjects' BMI, waist circumference and waist-to-hip ratio were measured at the study's start, [researchers] followed 13,549 middle-aged black and white men and women in four U.S. communities from 1987 through 2005. Participants started the study free of cancer and cardiovascular disease. During the follow-up period of about 19 years, 598 ischemic strokes occurred. The researchers calculated incidence rate - the number of new cases per 1,000 people per year - according to groups representing different degrees of obesity, using each obesity measure ... the correlation between increasing stroke incidence and increasing degree of obesity was apparent in both races and genders ... Individuals in the highest BMI category had 1.43 to 2.12 times higher risk of stroke. When waist circumference was used as a measure of obesity instead of BMI, those risk ratios ranged from 1.65 to 3.19; and 1.69 to 2.55 when waist-to-hip ratio was used. Thus, for any obesity measure, individuals in the highest category had approximately two times higher risk of stroke compared to the lowest category in each race-sex group."

Via EurekAlert!, another of the many ways in which excess fat tissue hurts you: "Obesity comes with plenty of health risks, but there's one that's perhaps not so well known: an increased risk of developing cancer, and especially certain types of cancer like liver cancer. Now, a group of researchers [have] confirmed in mice that obesity does indeed act as a 'bona fide tumor promoter.' They also have good evidence to explain how that happens. ... liver cancer is fostered by the chronic inflammatory state that goes with obesity, and two well known inflammatory factors in particular. The findings suggest that anti-inflammatory drugs that have already been taken by millions of people for diseases including rheumatoid arthritis and Crohn's disease may also reduce the risk of cancer in those at high risk due to obesity and perhaps other factors as well ... [Researchers were] able to trace the source of obesity's tumor-promoting effect to a rise in two inflammatory factors known as IL-6 and TNF. Obese mice lacking either the TNF receptor or IL-6 don't show the same rise in liver cancer. Those treatments also led the mice to accumulate less fat in their livers, he said. ... They still get fat, but the distribution of the fat is different. The fat goes to other places, but not to the liver."

REVISITING P66(SHC) MICE (January 21 2010)
You might recall that p66(Shc) mice are long-lived for reasons that are still open for debate - they are a good illustration of the sheer complexity of attempting to safely extend life through metabolic manipulation, and the time taken to understand what is going on. Here is more on the subject: "Evidence is mounting that reactive oxygen species (ROS) produced because of stressful challenges could interfere with the proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in greater vulnerability to aging and neurodegeneration. Here we tested the hypothesis that p66(Shc-/-) mice, which have been described to have an extended life span and a high resistance to oxidative stress, might be less susceptible to the effects of inflammatory insults at adulthood. ... Overall, the greater resilience to inflammation-induced changes in the p66(Shc-/-) mutants might underlie the better health status and the greater longevity characterizing these mice." Chronic inflammation that increases with age - due to putting on visceral fat, or increasing disorder in the immune system - is a big issue. Protection against it is similarly important.

It is the common wisdom that people who practice calorie restriction don't tend to manifest minor illnesses like colds and the like - but I'm not aware of any study to back up that claim. A while back, research linked hunger hormone ghrelin with increased immune function, and here is another study on the topic of fewer calories leading to a more aggressive immune system: "researchers have discovered an elementary mechanism which regulates vital immune functions in healthy people. In situations of hunger which mean stress for the body's cells, the body releases more antimicrobial peptides in order to protect itself. ... his natural immune defence system is linked directly to the metabolic status via the insulin signalling pathway. ... If we have not eaten for a while or have to climb many stairs, the energy level of our cells drops and with it the level of insulin. The researchers from Bonn have now discovered that in the case of a low insulin level the FOXO transcription factor is activated. A transcription factor can switch genes on and off. FOXO switches genes for immune defence proteins on when energy is needed. These antimicrobial peptides (AMP) - not to be confused with antibodies - are subsequently jettisoned by the body's cells. They destroy possible pathogens by dissolving their cell walls." One would expect calorie restricted people to have more of this going on in their bodies.

A little cell biology research in the old school mode for you today: throw in some changes and see what happens. Here, the researchers build a case for the accumulation of advanced glycation endproducts (AGEs) with age (and especially with metabolic syndrome or type 2 diabetes) to interfere with the operation of heat shock proteins (HSPs). These HSPs are a vital component of the recycling and repair machinery that keeps cells operating well, and appear to be the root cause of the hormesis effect, wherein a little adverse stress put upon your biology inspires it to operate more effectively. Both calorie restriction and exercise appear to produce at least some part of their benefits on health and longevity through boosting the operation of HSPs. Here, then, is evidence for AGEs to have the opposite effect: "Nonalcoholic steatohepatitis (NASH) is a feature of metabolic syndrome. Advanced glycation end-products (AGEs) are formed by the Maillard reaction, which contributes to aging and to certain pathological complications of diabetes. A recent study has suggested that glyceraldehyde-derived AGEs (Glycer-AGEs) are elevated in the sera of patients with NASH. ... Among the intracellular Glycer-AGEs that were formed, heat shock cognate 70 (Hsc70) was identified as a GA-modified protein, and its modification reduced the activity of Hsc70."

A GLANCE AT CIRM FUNDING (January 20 2010)
From the Los Angeles Times: "The California Institute for Regenerative Medicine recently awarded 14 grants to stem cell-based projects that are close to being ready for clinical trials. Here are some of the projects. ... A team from City of Hope in Duarte plans to genetically modify the blood-forming stem cells of AIDS patients so that they can rebuild their immune systems with new T cells that aren't susceptible to HIV. ... Researchers from USC and UC Santa Barbara are growing human embryonic stem cells into retinal pigment epithelium cells that can replace damaged eye cells in patients with age-related macular degeneration. ... Scientists from UCLA, USC and Stanford are developing drugs to target the harmful stem cells that drive the growth of tumors in brain, colon and ovarian cancer. ... Researchers at Cedars-Sinai Medical Center in Los Angeles plan to inject heart-attack patients with concentrated amounts of their own cardiac stem cells, which naturally repair heart tissue."

Regularly infusing the body with large numbers of T cell immune cells has the potential to help with a range of issues, given that the immune system declines with age: recent research "provides new insights into how our immune system produces T cells, a type of white blood cell that is an essential part of the body's immune surveillance system for fighting infection. The findings pave the way for a new means of making purified T cells, which gets over one of many hurdles faced in the use of T cells in regenerative medicine and transplantations, and in addition will open up new avenues of research and applications in drug and toxicity testing in industry. ... It reveals for the first time how immature T cells can be grown without the need for supporting 'feeder' cells - these cannot be easily separated from T cell preparations, reducing their suitability for transplantation in the clinic. This may advance the field of regenerative medicine. ... This technology could enable the production of T cells for clinical applications such as their transplantation into immuno-compromised individuals."

Via ScienceDaily: researchers "have demonstrated that artificial muscles can restore the ability of patients with facial paralysis to blink ... the technique, which uses a combination of electrode leads and silicon polymers, could be used to develop synthetic muscles to control other parts of the body. ... electroactive polymer artificial muscle (EPAM) [is] an emerging technology that has the potential for use in rehabilitating facial movement in patients with paralysis. Electroactive polymers act like human muscles by expanding and contracting, based on variable voltage input levels. ... Facial muscles require relatively low forces, much less than required to move the fingers or flex an arm. ... The three-layered artificial muscle was developed by engineers [in] the 1990s. Inside is a piece of soft acrylic or silicon layered with carbon grease. When a current is applied, electrostatic attractions causes the outer layers to pull together and squash the soft center. This motion expands the artificial muscle. The muscle contracts when the charge is removed and flattens the shape of the sling, blinking the eye. ... researchers are now refining the technique on cadavers and animal models. They estimate the technology will be available for patients within the next five years."

The latest from the Immortality Institute, with updates on present projects after the introduction: "2010 has arrived and it is time to take stock of Imminst's position in the world of life extension. Thanks to generous member donations and an active website, Imminst grew its registration base and financial assets in 2009. This was accomplished during a poor economy and after spending large sums on two matching grants and student scholarships. We now have more funds and potentially more manpower to accomplish greater goals in 2010. The key to greater success will be transforming the activity of the forums into action in the real world. Contained within the daily discussions of life extension news and philosophy are a world of valuable ideas and actionable initiatives. I encourage everyone to formulate the many ideas into plans of action, post them in the Action Forum for evaluation, and then contribute some time to see the best ones through to success. A few minutes a week is all it takes to turn a good idea into a successful promotion, outreach effort, or fundraiser. Also, keep your eye out for more online charity contests in 2010. Facebook and other social networking platforms have proven to be great tools to promote charitable giving. Suddenly, just one click of the mouse can lead to serious grant money for Imminst and other like-minded organizations. Keep an eye out for periodic forum messages and emails containing information and instructions for competing in these contests. Let us make a bigger impact in 2010!"

An example of the sort of biochemical engineering research underway in this field: "the quest to create artificial blood is big business, with more than one billion pounds being spent over the last 20 years in an attempt to create a true alternative to blood. Among those around the globe seeking a viable blood alternative are scientists at the University of Essex who have just submitted a worldwide patent for their engineered hemoglobin. ... to date the world's scientists have failed to produce a safe alternative to blood. The reason for this failure, according to [the University of Essex researchers] lies in hemoglobin, the red molecule inside blood cells that carries oxygen around the body. Outside the protective environment of the red cell, hemoglobin can be toxic. Hemoglobin normally changes color from red to claret as it transfers oxygen around the body. However, when it is damaged the iron in hemoglobin is oxidized (like a car rusting) to produce dysfunctional brown and green products. ... Basically, hemoglobin produces free radicals that can damage the heart and kidneys. ... The trick with artificial blood is to modify the molecule to be less toxic, but still perform the vital role of carrying oxygen around the body."



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