Longevity Meme Newsletter, May 18 2009

May 18 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.



- Learning From the Past
- Present Attitudes to Engineered Longevity
- Kindle Editions of Fight Aging! and the Longevity Meme
- Exercise and Antioxidants
- Discussion
- Latest Healthy Life Extension Headlines


"According to the actuarial tables used by insurance companies, if you are in your 20s now you prob­ably have about 50 years more to live. If you are in your 40s, you have only about 30 years more and if you are in your 60s your life-expectancy is only about 10 years. These tables are based on averages, of course - not everybody dies precisely at the median age of 72.5 years - but these insurance tables are the best mathematical guesses about how long you will be with us. Right? Wrong. Recent advances in gerontology (the science of aging, not to be confused with geriatrics, the treatment of the aged) have led many sober and cautious scientists to believe that human lifespan can be doubled, tripled or even extended indefinitely in this generation. If these researchers are right, nobody can predict your life expectancy. All the traditional assumptions on which the actuarial tables rest are obsolete. You might live a thousand years or even longer."

The words above were written in 1978 by Robert Anton Wilson, one of a number of advocates for engineered longevity who have since aged to death. They looked at the pace of research in their era and saw themselves at the dawn of an age of biotechnology and radical life extension. They were wrong, and they were too early - which should make all of us at least a little uncomfortable. How are we any different? What can we point to that shows us to be in a better situation, actually at the dawn of the era of engineered longevity, rather than once again a generation too early?


"The Strategies for Engineered Negligible Senescence (SENS) could have been proposed in the 1970s, in a very similar way to their present form, had some determined fellow existed with the keys to research vaults and a great deal of time to assemble all the necessary insights. ... But in the 1970s, getting proto-SENS to work in mice would not have been a billion-dollar, ten year proposal as is presently the case. It would have required a far greater initiative, one to rival the space program or the formation of the NIH. In 2009 we live in an age of biotechnology and life science capabilities that is far, far removed from the rudiments of 1970. Work that today can be achieved by a single postgrad in a few months for a few tens of thousands of dollars would have required entire dedicated laboratories, years of labor, and tens of millions of dollars in the 1970s.

"Today, we can point to such things as successful efforts in the laboratory to safely replace all damaged mitochondria in living animals, for example. The Fight Aging! archives are rife with examples of the sort of barnstorming experimentation and success taking place in the life sciences over the past few years: cells reprogrammed, mechanisms uncovered, organs created, and so forth. We know that the present state of biotechnology is sufficient to make real progress in the repair of aging, and that this technology base is advancing much more rapidly than in the past."



Links to a couple of long posts on today's society and the prospects for greatly extending our healthy lives through scientific research and medical development:


"Most people who think it would be 'unnatural' to cure aging so that people can live for centuries probably do not think brushing their teeth is 'unnatural', but fundamentally it's the same thing. In both cases, one is using tools created by human intelligence to prevent damage which would otherwise slowly degrade one's health. Since we understand what causes tooth decay, it's perfectly natural for us as intelligent creatures to make and use tools to avoid it. The aging process is far more complex, as are the tools we will need to develop to stop it, but the principle is the same."


Since it was easy to do, I've set up the Longevity Meme News and Fight Aging! feeds to be accessible on Kindle devices. Whatever (very) minor revenue this produces will be donated to either the Methuselah Foundation or SENS Foundation. Links are in the following post:



Our biochemistry is exceedingly complex and far from fully understood. This means that much of its operation is counter-intuitive. See here, for example, recent findings on exercise and antioxidants (but be sure to read the whole thing, because there's much more than just the quote below):


"So, what actually causes [the beneficial effects of exercise on metabolism]? There has to be a signal (or set of signals) down at the molecular level that tells your cells what's happening, and initiates changes in their metabolism. One good candidate is the formation of reactive oxygen species (ROS) in the mitochondria. Exercise most certainly increases a person's use of oxygen, and increases the work load on the mitochondria (since that's where all the biochemical energy is coming from, anyway) ... as it turns out, antioxidant supplements appear to cancel out many of the beneficial effects of exercise. Soaking up those transient bursts of reactive oxygen species keeps them from signaling."


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!




Alzheimer's Looks as Avoidable as Diabetes (May 15 2009)
As this ScienceDaily release notes, Alzheimer's disease and type 2 diabetes share many of the same risk factors. Pack on the fat and stop exercising and you too can suffer metabolic syndrome that later blossoms into these and other degenerative conditions. "Modern societies face the increasing burden of age-related diseases, in particular Alzheimer’s disease (AD) and type 2 diabetes (T2D). There is some evidence that the causes underlying both diseases are linked. Do AD and T2D represent the endpoint of aged, exhausted, and dysfunctional cells having reached their maximal life expectancy or are AD and T2D the consequences of living in superabundance including excessive food supply, work demands, psychosocial stress, and an excessive sedentary life style? ... The mechanisms relating [excess fat tissue] and T2D to AD may include hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease, and products of adipose tissue metabolism. The implication of these associations is that a large proportion of the world population may be at increased risk of AD given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However these associations may also present a unique opportunity for prevention and treatment of AD."

What Can Be Achieved With Artificial Tissue? (May 15 2009)
Scientists are presently working towards artificial cells, and here we have an example of work on an artificial extracellular matrix. Building an appropriately complex and supporting scaffold - a matrix - for tissue engineered organs is a challenge presently facing researchers. So what could be done with the ability to turn out extracellular matrix to order? "The tissue in our bodies has a combination of traits that are very hard to recreate in synthetic materials: It is both soft and very tough. A team [has] now developed a novel, highly porous, sponge-like material whose mechanical properties closely resemble those of biological soft tissues. ... it consists of a robust network of DNA strands and carbon nanotubes. ... Different protein morphologies in the extracellular matrix produce tissue with a wide range of stiffness. Implants and scaffolding for tissue growth require porous, soft materials - which are usually very fragile. Because many biological tissues are regularly subjected to intense mechanical loads, it is also important that the implant material have comparable elasticity in order to avoid inflammation. At the same time, the material must be very strong and resilient, or it may give out. The new concept uses DNA strands as a matrix; the strands completely 'wrap' the scaffold-forming carbon nanotubes ... This results in materials that are as elastic as the softest natural tissues while simultaneously deriving great strength from the robust DNA links."

The Continuum of Calorie Restriction (May 14 2009)
An interesting piece from innovations report: "Moderate calorie restriction causes temporal changes in the liver and skeletal muscle metabolism, whereas moderate weight loss affects muscle ... 22 obese patients were randomized to a high-carbohydrate or low-carbohydrate [calorie restricted] diet. ... insulin action, cellular insulin signaling and [liver] triglyceride (IHTG) content [were determined] ... Researchers found that short-term CR caused a rapid decrease in IHTG content, an increase in [liver] insulin sensitivity and a decrease in endogenous glucose production rate, whereas longer-term CR and a moderate 7 percent weight loss improved skeletal muscle insulin sensitivity in conjunction with an increase in cellular insulin signaling. The effect of moderate CR in obese patients with either a low-fat or low-carbohydrate diet on metabolic function is a continuum, with differential effects on specific organ systems." The same sort of result most likely holds in people of normal weight, based on what I know of past research. Some benefits of CR take effect rapidly, some not, and the precise details vary with the details of diet.

Political Philosophy and the Science of Longevity (May 14 2009)
Of interest to those who like to see how the other half thinks about engineered longevity, here is a long post from a political philosopher in the "social justice" (i.e. forced redistribution of property) camp: "One of Rawls's 'simplifying' assumptions is that all the participants in the social contract are healthy, productive members ... Rawls invoked this simplifying assumption to help bracket particular complexities like healthcare, and in so doing come to an understanding of how wealth and income should be distributed and the weight to place on rights and freedoms. The problem is that this one simplifying assumption pretty much erases many of the central questions of justice that are in need of being addressed. To bracket them, so that attention can be placed on wealth, income and rights and freedoms gives one the impression that science and health policy are secondary, or even tertiary concerns. And that has certainly been the (unfortunate) consequence for the field 4 decades later. The reality today is that the inborn aging process is now the major risk factor for disease and death after around age 28 in the developed countries and limits average life expectancy at birth to approximately 85 years ... Aging predisposes our bodies to fall apart, making us vulnerable to chronic diseases like cancer, heart disease and stroke. Advances in evolutionary biology point us in the direction of potential interventions in the aging process that could expand the opportunities humans could have for health. Our neglect of human biology and science in general is unjustified."

A Science For Life Extension Foundation Meeting (May 13 2009)
Researcher Leonid Gavrilov recently visited Russia to talk to the folk behind the Science Against Aging initiative. Here, he translates a meeting report: "Aging -- not a destiny! This was the title of a charitable meeting of the Foundation 'Science for Life Extension', which took place in a comfortable informal environment of the Tsurtsum Cafe at the Winery place (Moscow, Russia). It is this environment, which provided an opportunity for guests to absorb the vast amount of knowledge about human aging, and about the opportunities offered, and to be offered by science to combat it. The purpose of the meeting - to allow guests (which were people of many different professions - politicians, businessmen, designers, representatives of the various foundations) to learn as much about aging as possible, and to learn that aging could be defeated in the foreseeable future. Knowledge leads to action, and therefore the second goal of the Foundation 'Science for Life Extension' was to get as many supporters and partners as possible. ... The chairman of the Board of Trustees of the Foundation, Michael Batin shared with guests his plans, and the most important of them - the development of an integrated interdisciplinary program 'Science against aging'."

The Immune System and Gender Differences in Longevity (May 13 2009)
There are plenty of candidate mechanisms for the well-known longevity gap between men and women. Here is another - the potency of your immune system: "women have a more powerful immune system than men. In fact, the production of estrogen by females could have a beneficial effect on the innate inflammatory response against bacterial pathogens. ... More specifically, estrogen naturally produced in women seems to block the production of an enzyme called Caspase-12, which itself blocks the inflammatory process. ... The positive effect of natural estrogen on our resistence to infection is also exhibited with synthetic hormones such as 17-beta-estradiol. This finding might therefore open the door to new therapeutic applications that reinforce the immune system." A more robust immune system can go a long way to boosting life expectancy. In addition to dealing with pathogens, the immune system is also responsible for eliminating damaging senescent cells and cancer cells, for example.

Scaffolds and Cartilage Regeneration (May 12 2009)
From the Technology Review: "Our joints are one of the first body parts to suffer the inevitable ravages of aging: cartilage may be torn in overzealous basketball games or slowly worn away over years of use. Scientists are now experimenting with a combination of stem cells and novel scaffold materials designed to mimic real tissue, in hopes of permanently vanquishing the pain that accompanies this damage and perhaps preventing the onset of arthritis. In animal models, these transplants appear to spur regeneration of cartilage that better resembles native tissue. ... In a recent pilot experiment in pigs, researchers sutured the cell-laden scaffolds over damaged cartilage in the animals' knees. Six months later, new tissue had formed, with a smooth surface and mechanical properties similar to those of native cartilage. The tissue also expressed molecular markers characteristic of normal cartilage. ... he aims to begin human tests in the next two years. First, his team must do additional studies in large animals, such as goats or sheep, over a longer period of time, to make sure that the treatment is safe and effective."

Upgrading Our Biochemistry (May 12 2009)
Are there comparatively simple, localized tweaks to human biochemistry that could be tested and implemented in a short enough timeframe to benefit the health and longevity of those of us reading this today? Perhaps. This might be one of them: "Oxygen metabolism (the process by which living cells produce energy), leads to the production of highly reactive oxygen species (ROS), which can cause significant neurodegenerative damage in cells that are unable to protect themselves. This is seen most remarkably in aging cells, which experience both an increase in ROS production and a decrease in defense mechanisms, a condition known as oxidative stress. Through their examination of cells in the laboratory, the researchers concluded that potassium channels are targets of ROS, resulting in modification to the cell that causes neuronal dysfunction. The researchers showed that by modifying a single cysteine residue, they could make the potassium channel resistant to oxidation, thereby allowing for normal functioning of the nervous system."

Klotho in Old Humans (May 11 2009)
Researchers continue to investigate the klotho gene and the effects it may have on human longevity: "In mice a defect of Klotho gene expression results in multiple aging-like phenotypes including short lifespan, osteoporosis and atherosclerosis, while its over-expression suppresses aging and extends lifespan. Contrasting data have been reported as far as the importance of the functional variant of Klotho termed "KL-VS" on human longevity, depending on the average age of the old subjects that were compared with young controls. We therefore performed a study on a large Italian population sample including people from very young to very old age (centenarians). ... found a significant increase of the heterozygous Klotho genotype in the class of elderly [non-centenarian] people compared to young controls. On the contrary, no difference was present between centenarians and young controls. [This is] is compatible with the hypothesis that this KL-VS heterozygous genotype is favorable for survival in old people, its beneficial effect decreasing thereafter. ... alleles and genotypes involved in aging and longevity may exert their biological effect at specific time windows." So evidence suggests one klotho variant helps humans survive into old age, but don't help us make it to extreme old age - which raises more questions as to the underlying mechanisms.

Autophagy Versus Cholesterol (May 11 2009)
Chris Patil of Ouroboros adds some pertinent thoughts to a recent Fight Aging! post on macroautophagy research: "stimulation of one autophagic pathway can reduce plasma lipoproteins and triglycerides ... Is the decrease in blood lipids a consequence of every cell in the body upregulating autophagy and therefore needing more cholesterol and triglycerides in order to rebuild membrane-bound organelles, or is this a consequence of the drug acting mainly on specific tissues/organs? ... Is there a down side? I'm wondering whether the effects of accelerating macroautophagy will be uniformly beneficial to all cell types. I'm especially concerned with respect to cognitive function: In worm and fly, age-related neuronal death is mediated by autophagy and there's building evidence that the same is true in mammals. (This makes sense: Cellular homeostasis is a balance between creation of new components and destruction of old ones; one can easily imagine a delicate and finicky cell like a neuron losing control of this balance if the rate of degradation were to suddenly rise)." On the other hand, wouldn't calorie restriction cause issues due to its boost to autophagy if that were the case? We'd all like to see life span studies in mice, I think.



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