Longevity Meme Newsletter, November 10 2008

November 10 2008

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.



- Investigating Mitochondrial Uncoupling
- The Slow Diffusing of Transhumanist Ideals
- Linking Inflammation and Parkinson's Disease
- Discussion
- Latest Healthy Life Extension Headlines


As researchers seek the mechanisms by which natural longevity varies due to circumstances of diet and exercise, the process of mitochondrial uncoupling has attracted attention:


"Mitochondrial uncoupling is much as it sounds; a feedback mechanism in which processing of food within mitochondria is disconnected from ATP production; energy from food goes elsewhere, as heat for example. Because this affects free radical production, it seems to be important in tissue aging."

But the picture remains unclear. Studies show that uncoupling appears to increase during the practice of calorie restriction, but that inducing greater uncoupling through genetic engineering only seems to increase average life span in laboratory animals - unlike calorie restriction, which increases maximum life span as well. To add to the mystery, a drug that increases uncoupling does actually increase maximum life span in mice. It is unclear as to why one method produces different results from another.

Here we have a process emblematic of the state of calorie restriction research at the present time: scientists are documenting numerous mechanisms that show promise for engineered longevity, each discovered while investigating calorie restriction with the tools of modern biotechnology, but which are not yet fully understood.


Transhumanists organize and support many of the most interesting young initiatives of this new century. Some will go on to be the behemoths in their fields in years to come:


"If you look around at the serious efforts to make progress in longevity science or other means of postponing permanent death, you'll find members of the transhumanist community involved and amongst the most vocal supporters: the Methuselah Foundation; Alcor and the Cryonics Institute; the Immortality Institute. Similarly in the fields of strong artificial intelligence and advanced nanotechnology - organizations like the Singularity Institute, the Future of Humanity Institute and the Center for Responsible Nanotechnology are outgrowths of the transhumanist community of the 80s and 90s. Collectively these organizations and others have raised tens of millions of dollars over the years.

"All of these ideals - bioengineering, the defeat of aging, enormously lengthened healthy life spans, artificial beings, molecular manufacturing, and much more - will come to pass. Too many people are thinking about these goals now for any but the impossible to vanish from the horizon. It's just a question of when it all comes to pass - which is a very big question when it comes to the development of medical technologies that can rescue us from aging to death. Soon enough, or too late? What are you doing to help things along?"


More good reasons to try to reduce your burden of chronic inflammation:


"Patients with Parkinson's disease (PD) have elevated levels of the protein called alpha-synuclein in their brains. As the protein clumps, or aggregates, the resulting toxicity causes the death of neurons that produce the brain chemical dopamine. Consequently, nerves and muscles that control movement and coordination are destroyed. It looks possible that the reason behind all this clumping synuclein is chronic inflammation - that catch-all bugbear that appears to contribute to all the major diseases and degenerations of aging."

There exists more than enough evidence to demonstrate that chronic inflammation is bad for your health and longevity, even if this proposed link to Parkinson's is refuted. Making life choices to minimize inflammation as best you can seems a sensible response to the research findings amassed to date:



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/

The Most Important Research (November 07 2008)
From the ExchangeMorning Post, a statist, public funding viewpoint on longevity science: "Learning how to turn back time - or at least how to slow the aging process - may be more important for improving our overall health than the discovery of a cure for cancer ... there are real, tangible benefits, for society as well as individuals, to slowing down the aging process. 'By extending the life span, people would remain in the workforce longer, personal income and savings would increase, age entitlement programs would face less pressure from shifting demographics, and national economies would flourish' ... almost half of the current population over 75 years old is limited in their activity by chronic conditions, with costs to society set to rise dramatically ... Given the current predicament we face, we can't ignore the call to tackle aging more aggressively. To those who ask: 'Can we really afford to invest more in such research?' we can reply: 'Can we really afford not to tackle aging?' ... the greatest obstacle will be convincing the general public that slowing the aging process is both feasible and deserving of a larger share of the funds available for scientific research."

An Overview of Cryonics (November 07 2008)
A good article on cryonics from Engineering and Technology: "The field of cryonics, which made its debut in the 1960s, continues to push the envelope and search for a solution to death. The process consists of preserving legally dead humans or pets at very low temperature (below -130C) in the hope that future science can restore them to life, youth, and health. ...The advancement of medicine and science is so much faster than it used to be. Science fiction is becoming science fact on a daily basis. All of a sudden, cryonics doesn't look quite so far-fetched. ... Most cryonicists believe reanimations will occur within 50 to 100 years for those currently being cryopreserved. ... Within that time frame, virtually all current diseases should be curable and elderly people can probably be rejuvenated to a youthful condition. ... With full disclosures and signed consent, [cryonics] is highly ethical. When you think about the grand scheme of things, cryonics is a lot more conservative than burial or conventional cremation. ... Tissue preserved at the temperature of liquid nitrogen does not deteriorate, even after centuries of storage. Therefore, if current medical technology can’t keep us alive, we can instead choose to be preserved in liquid nitrogen, with the expectation that future medical technology should be able to reverse any cryopreservation injury and restore good health. If sceptics don't want to pursue this area, that's fine, but I ask them not to interfere with my own efforts to save the lives of myself and the people I love."

Cells as Vectors For Targeted Therapies (November 06 2008)
The possibilities of bioengineering are endless, and one of the most energetic branches of the research community is involved in developing methods of precisely targeting therapies: "MIT engineers have outfitted cells with tiny 'backpacks' that could allow them to deliver chemotherapy agents, diagnose tumors or become building blocks for tissue engineering. ... The polymer backpacks allow researchers to use cells to ferry tiny cargoes and manipulate their movements using magnetic fields. Since each patch covers only a small portion of the cell surface, it does not interfere with the cell's normal functions or prevent it from interacting with the external environment. ... researchers worked with B and T cells, two types of immune cells that can home to various tissues in the body, including tumors, infection sites, and lymphoid tissues - a trait that could be exploited to achieve targeted drug or vaccine delivery. ... The researchers found that T cells with backpacks were able to perform their normal functions, including migrating across a surface, just as they would without anything attached. By loading the backpacks with magnetic nanoparticles, the researchers can control the cells' movement with a magnetic field."

Towards a Rejuvenated Thymus (November 06 2008)
One approach to the issue of declining naive T-cells with age - and consequence failure of the immune system - is to boost production by manipulating the thymus: "a key gene may be crucial to maintaining the production of the thymus and its disease-fighting T-cells after an animal's birth. The discovery could help scientists find out how to turn the thymus back on so it could produce T-cells long after it normally shuts down most of its function, which, for humans, occurs by early adulthood. If the finding leads to further ways to manipulate the gene, the result could be a new avenue for the body to fight disease more effectively as the body ages. ... Such things as infectious diseases, inflammation and heart problems are all related to immune response. You don't have to think far to see how understanding the effect of this gene could affect the quality of life for older people and others as well. ... If [physicians] were able selectively to turn T-cell production back on, then many diseases that currently afflict older people could become manageable if not, in cases, entirely absent."

Boosting the Aging Immune System (November 05 2008)
Many research groups are working on ways to boost the effectiveness of an exhausted immune system - due to either chronic viral infection or aging - without necessarily aiming to address the root causes: "In contrast to most normal somatic cells, which show little or no telomerase activity, immune cells up-regulate telomerase in concert with activation. Nevertheless, during aging and chronic HIV-1 infection, there are high proportions of dysfunctional [immune cells] with short telomeres ... exposure of CD8(+) T lymphocytes from HIV-infected human donors to a small molecule telomerase activator (TAT2) modestly retards telomere shortening, increases proliferative potential, and, importantly, enhances cytokine/chemokine production and antiviral activity. The enhanced antiviral effects were abrogated in the presence of a potent and specific telomerase inhibitor, suggesting that TAT2 acts primarily through telomerase activation. Our study is the first to use a pharmacological telomerase-based approach to enhance immune function."

How Inflammation Causes Cancer (November 05 2008)
Chronic inflammation, a source of age-related cellular and molecular damage, is linked to most of the common age-related conditions. It might be thought of as a form of rust that hastens the failure of the machinery. Here, researchers show how inflammation causes one specific form of cancer: "evated levels of a single proinflammatory cytokine, an immune system protein called interleukin-1 beta (IL-1beta), can start the progression towards stomach cancer. ... accumulation of IL-1beta, which is induced by infection with the bacterium Helicobacter pylori (H. pylori) in the gastrointestinal tract, is a significant contributor to the onset of stomach cancer ... We show in this study that IL-1beta works by activating a type of white blood cell known as myeloid derived suppressor cells (MDSCs), which in our study appeared to be strongly pro-inflammatory. Blocking IL-1beta or the myeloid (MDSCs) cells may represent a potential strategy to prevent stomach cancer ... these findings help to explain why only a small percentage of those with H. pylori infection go onto develop stomach cancer - a genetic predisposition for high expression levels of proinflammatory cytokines." So a ugly feedback loop of accelerating inflammation and damage is kicked off by an initial event and predisposition to reach the threshold that will activate that loop.

After Resveratrol, SRT1720 (November 04 2008)
From EurekAlert!: "A drug designed to specifically hit a protein linked to the life-extending benefits of a meager diet can essentially trick the body into believing food is scarce even when it isn't .. SRT1720, which acts through the protein SIRT1, enhances running endurance in exercised mice and protects the animals against weight gain and insulin resistance even when they eat a high-fat diet, the researchers report. The drug works by shifting the metabolism to a fat-burning mode that normally takes over only when energy levels are low. ... It also helps lay to rest a long-standing controversy in the scientific world over the metabolic benefits of [resveratrol]. Resveratrol also acts on SIRT1, but its influence on other metabolic actors had left room to question exactly how it works. .. There has been a lot of controversy in the field about resveratrol action. We find that the majority of the biology of resveratrol can be ascribed to SIRT1. ... While SIRT1 might not explain all of resveratrol's effects, the new results suggest that the central metabolic protein is responsible for about '80 percent of the picture.'" Which suggests that resveratrol and SRT1720 are not capturing all of the biochemical benefits of calorie restriction.

Posts Wanted For Hourglass V (November 04 2008)
The fifth Hourglass blog carnival on aging and longevity science draws near - remember to send in your submissions. "Hourglass is a monthly blog carnival devoted to biogerontology. Its main purpose is to provide a regular showcase for the growing number of excellent blog posts about the biology of aging. We are soliciting entries in the general subject area of aging and biogerontology: 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. ... Just about the only sorts of things we'll turn away are quackery and promotions of commercial products (including brazenly for-profit websites of no redeeming scientific value). So, no growth hormone commercials or glowing reviews of your own book, please. ... Submissions should be emailed to [hourglass.host][at][gmail][dot][com]."

Incremental Improvements in Scaffolding (November 03 2008)
From the MIT Technology Review: "Engineering heart tissue presents particularly tough problems for researchers, since the heart is an active organ ... scaffolds designed for other kinds of tissues did not have the right mechanical properties for heart tissue. Heart tissue must be flexible enough to change shape as the heart contracts, but also strong enough to withstand the intense forces generated by these contractions. ... The researchers designed the scaffold to encourage cells to align themselves in the same direction to better mimic this property of natural heart muscle tissue. Using a laser cutting technique, they created a pattern of oblong holes in the polymer; the result is a flexible, honeycomb-like structure that is stiffer in one direction than another. ... just as rowers line up in one direction to propel a boat forward, 'all the heart muscle cells in a given region have to be lined up and contracting in the same direction' in order for the heart to beat efficiently. The honeycomb-like scaffold [represents] a 'substantial jump' toward that goal ... If we had a biodegradable biomaterial, which had beating heart cells, we might be able to return function to [damaged parts] of the heart."

A General Interest Calorie Restriction Article (November 03 2008)
As the science advances, these articles get more positive. Recall the ridicule heaped upon the practice of calorie restriction even just a few years ago. "Some people are doing it strictly to enhance longevity. Others do it to avoid age-related disease, or because they already have diabetes, high cholesterol or clogged arteries and want to clean up their bodies by using diet. ... In rich countries, 90 percent of the population probably eats, on average, about 50 percent too much. ven if they were to reduce their calorie intake by half, they would still only be at baseline ... A wealth of scientific evidence has confirmed that maintaining that balance helps prevent type-2 diabetes, cardiovascular disease and cancer. But experiments with both animals and humans have also shown that pushing one's calorie intake 10 to 20 percent below that baseline threshold -- without lowering nutrients -- may provide additional health advantages. ... Will this add 10 years to your life? Nobody knows. But one thing is sure -- calorie restriction will help you reach your maximum lifespan potential, which is different for all of us depending on our genetic profile."



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