LONGEVITY MEME NEWSLETTER
September 22 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.
- An Interesting Calorie Restriction Demonstration
- Also, Try Not to Stab Yourself Repeatedly
- A Little of the Latest Longevity Science
- Latest Healthy Life Extension Headlines
AN INTERESTING CALORIE RESTRICTION DEMONSTRATION
The practice of calorie restriction (CR) - eating fewer calories while still obtaining an optimal level of micronutrients - changes the operation of your biochemistry for the better quite rapidly. Researchers at the CALERIE human CR study have been working to quantify those changes by culturing cells on serum extracted from study participant blood plasma:
"Two pilot studies were undertaken to examine the effects of [alternate day fasting and calorie restriction] on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human [cells] and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period). ... [This] resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity."
As of late 2008, I'd guesstimate that something in the order of one to two billion dollars have been invested into developing drugs that will produce some fraction of the effects of calorie restriction on mammalian biochemistry - such as increasing the expression of Sirt1. They aren't done yet, and years of trials and further development lie ahead. Most people can get these benefits today and for free, however, by simply eating a less calorie-packed diet. You should look into it: calorie restriction isn't anywhere near as hard as those who have never tried it make it out to be. You can find an introduction at the Longevity Meme website:
ALSO, TRY NOT TO STAB YOURSELF REPEATEDLY
Words of wisdom:
"On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lecture of V. Nicita-Mauro on Smoking, health and ageing is summarized. Smoking represents an important ageing accelerator, both directly by triggering inflammatory responses, and indirectly by favouring the occurrence of several diseases where smoking is a recognized risk factor. Hence, non-smokers can delay the appearance of diseases and of ageing process, so attaining longevity.
"Forms of slow self-destruction are many and varied amongst we humans: smoking, not practicing calorie restriction, failing to keep up a good relationship with a physician, piling on the visceral fat, failing to exercise, and so forth. The vast majority of people are quite comfortable engaging in habits that cause great harm to the old person they will one day be - cutting off years or even decades of health. This is all a good example of time preference at work: we are hardwired to deeply discount the value of the future, even when it's our own future. What we don't value, we squander - you can see that maxim in action everywhere."
A LITTLE OF THE LATEST AGING RESEARCH
Two items for those of you who like to keep track of the latest research into the biochemical roots of aging and longevity:
"How lipofuscin causes problems in neurons and muscles is not clear, but it's believed that this is garbage that, in time, compromises the normal function of the lysosome. And we know the lysosome is important for all kinds of cell biology, particularly the recycling of intracellular components, so if it's damaged, the cell is going to suffer. ... Indeed, abnormal accumulation of lipofuscin is associated with a range of disorders including Alzheimer's disease, Parkinson's disease, and macular degeneration (a degenerative disease of the eye) and also contributes to the aging process."
"Regular readers should by now know that accumulating damage to the mitochondria, the power plants of your cells, contributes to degenerative aging. ... Regular readers should also recall the evidence for glycation as a bad thing for your long term health. ... Last year, I mentioned a demonstration of life extension in nematode worms achieved by reducing the level of glycation. Researchers increased the levels of a natural enzyme called glyoxalase that reduces the levels of glycated chemicals: this is somewhat analogous to using antioxidants to reduce oxidative stress and levels of free radicals. Today, I noticed the following paper, which theorizes that glycation also causes damage to mitochondria, possibly by preventing vital mitochondrial proteins from doing their jobs, and that lower levels of glycation also reduce the problems that are characteristic of mitochondrial damage."
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!
LATEST HEALTHY LIFE EXTENSION HEADLINES
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/
Ouroboros on Telomere Length (September 19 2008)
Ouroboros discusses complications inherent in measuring telomere length: "regarded as a potential biomarker of aging, there is a growing body of evidence indicating that shorter telomeres are associated with various diseases, including cancer, infectious disease, psychological stress, and cardiovascular disease. In cardiovascular disease in particular this had led to the hypothesis that premature, or accelerated, aging of the vasculature is a major contributing factor. While a handful of papers have estimated telomere length in specific vascular tissues, the numbers and sizes of samples in these studies are usually small, due to the limitations in obtaining the tissues and cells of interest. Thus, telomere length in genomic DNA obtained from circulating leucocytes is routinely used as a proxy for telomere length in other tissues. However, the inflammatory processes involved in disorders such as cardiovascular disease can result in increased white cell turnover, raising the possibility that the shorter telomeres measured simply reflect recent replicative activity." Nothing in biochemistry is ever as simple as we'd like it to be.
Lurking Behind the TOR Gene (September 19 2008)
Researchers have known for a few years that the TOR gene is important in calorie restriction and other related ways of extending healthy life. Recent research follows the chain of biochemical cause and effect beyond TOR: "In C. elegans, the tiny roundworm that our lab studies, as well as some other animals, a loss of TOR has been shown to slow aging. Our work with C. elegans reveals that TOR depends on a second gene called pha4/FoxA to control the aging process ... When there's lots of food, TOR gets active, which decreases the action of pha4/FoxA down the line, and that in turn shortens the lifespan of C. elegans. When there's little food, there's little TOR and more pha4/FoxA, and that results in a longer lifespan. ... Many organisms have a TOR gene and a gene similar to pha4/FoxA, such as single-cell yeasts, roundworms, and mammals including humans. In mammals, FoxA controls cell metabolism and there is a lot of it in breast and prostate cancers. The findings of this research establish that animals use both genes to sense the amount of food that is available and control the length of lifespan. Further research will be required to establish whether a similar relationship between these factors can control metabolism, longevity or disease in humans."
Protecting Donations for Longevity Science (September 18 2008)
From the Methuselah Foundation blog: "These are uncertain times in the financial markets. We here at the Methuselah Foundation strive to ensure that your donations will retain their value through equity market volatility, allowing them to be put to good use in the MPrize fund or for SENS research. ... The Methuselah Foundation's funds have been and are fully invested in FDIC insured bank bonds and accounts diversified across many major well capitalized banks. No one bank holds more than $100,000, thus ensuring 100% FDIC coverage of the entire corpus.
No CD has a maturity of longer than 12 months, and the bonds are laddered to mature (and roll over) across the calendar on a periodically smooth basis. We have recently modified the size of new CD purchases down from $100,000 to $95,000 so that it will not exceed the $100k FDIC insurance threshold as interest accrues. In the unlikely case of a bank default, the Methuselah Foundation will lose neither principal NOR accrued interest. When we have received donations of marketable securities (stocks) we have usually sold them quickly rather than holding them. At this point, September 2008, the Methuselah Foundation's funds are entirely in FDIC insured accounts diversified over more than 25 different banks. We hold no stocks, uninsured bonds, or any other 'at risk' instruments."
Early Experiments in Cryonics (September 18 2008)
Depressed Metabolism takes another look at the early days of cryonics: "The question of whether cryonics 'works' or not is too general and hides the point that progressive breakthroughs can make the concept more plausible. ... During its existence as a research program, cryonics researchers have shown great interest in recovering animals from ultra-profound hypothermic temperatures (lower than 5 degrees Celsius). The ability to routinely lower the temperature of mammals to temperatures close to zero degrees Celsius and recover them without adverse effects to the brain does make the initial stages of cryonics reversible. ... Less known than those record setting experiments are earlier explorations in cryonics into whole body asanguineous hypothermia. The following document by cryonics researcher and Alcor patient Jerry Leaf documents a Trans Time experiment during the early days of total body washout experiments in cryonics. This account was published in the November/December 1977 issue of Long Life Magazine."
Struggling to Break Out of the Old Paradigm (September 17 2008)
From RedOrbit, an example of someone caught halfway between paradigms: learning about the potential of longevity science, but having trouble envisaging the changes it will herald for institutions of insurance, development, and regulation. "Currently our drug development and approval systems aim at disease-specific treatments. Indeed, the Food and Drug Administration approves medications only for specific indications, and 'mortality,' a universal condition, would seem unlikely to qualify under the current system. Further, if senescence begins in one's 30s but the outcome (that is, death) can be measured only in one's 70s or 80s, how will researchers be able to perform timely clinical trials in humans? ... Health insurance is based on the principle of risk pooling. Because nobody can be certain that they will remain healthy, the disease-free are willing to share the cost burden with the sick ... But if resveratrol-like drugs are recommended for everybody over 30 at risk for mortality (a universal condition), there would be no risk pooling." When you catch yourself asking "how will this ever fit?" then the answer is usually "it won't fit, and will never fit in the present structure, because things will change in the future so as to accommodate it."
Learning From AIDS (September 17 2008)
There are similarities between the progression of AIDS and what happens (more slowly) to our immune systems with aging. Forced overactivation and exhaustion of resources are the focus here. AIDS researchers are making steps towards understanding mechanisms that would allow the immune system to be tuned down for specific threats, to prevent it grinding itself into oblivion. "During both HIV infection in humans and SIV infection in macaques, the host immune system becomes highly activated, experiences increased destruction and decreased production of key immune effector cells and progressively fails as a result. In contrast, natural hosts for SIV infection, like sooty mangabeys, do not exhibit aberrant immune activation and do not develop AIDS despite high levels of ongoing SIV replication. ... sooty mangabeys, dendritic cells produce much less interferon alpha - an alarm signal to the rest of the immune system - in response to SIV. As a result, the dendritic cells are not activated during the initial or chronic stages of SIV infection, and mangabeys fail to mount a significant immune response to the virus." It seems reasonable to expect this knowledge to be applicable to the long-term response to CMV in humans, an important contributer to age-related immune system failure.
A Better Lifestyle Means More Telomerase? (September 16 2008)
The San Francisco Chronicle reports on an intriguing, if small, study: researchers "studied the levels of an enzyme called telomerase in the prostate tissue of the 30 cancer patients who had volunteered to follow a low-fat diet, exercise moderately and reduce their stress. After only three months, 24 patients showed a highly significant increase in their telomerase levels - an indication that the cell-protecting telomeres in their cells were being restored. ... The long telomere proteins protect the ends of chromosomes in the body, but they shorten naturally and ultimately die unless the telomerase enzyme acts to repair them and increase their length. ... even with only 30 patients [the] association between their extremely healthy habits and the increased amount of telomerase proved highly [statistically] significant." Telomerase is apparently also involved in reducing age-related damage to mitochondria, which in turn slows the rate at which failing mitochondria cause telomeres to shorten.
Mitochondrial Function and Aging (September 16 2008)
Those of you familiar with the mitochondrial free radical theory of aging - damage to mitochondrial DNA leads to loss of function and a spreading chain of biochemical dysfunctions - will notice a subtle disconnect between this research and the popular science view of mitochondrial function and aging, as outlined in this Boston Globe article. The popular view is very much concerned with contribution to particular diseases, and in finding drugs that improve mitochondrial function as a way of slowing that contribution - without necessarily understanding why those drugs work. We know enough to do much better than that - repairing mitochondrial damage completely, for example, and thus totally removing its contribution to aging. But until the public at large realizes this, funding will continue to move towards the established old-school drug discovery programs. These programs focus on treating specific diseases of aging by patching over or slowing down root causes - as opposed than aiming to repair them fully.
More on FOXO3A (September 15 2008)
A little more depth on the recent association of FOXO3A with human longevity from Ouroboros: "Mutations in genes involved in the insulin/IGF-1 signaling pathway (IIS) improve longevity in animal models ... The authors hypothesized that single nucleotide polymorphisms (SNPs) in FOXO related genes could be responsible for the differing longevity phenotypes between the long-lived and average-lived [human] cohorts. Five genes, ADIPOQ, FOXO1A, FOXO3A, SIRT1, and COQ7 were selected as candidates, and three SNPs were analyzed per gene. Despite the small number of genes and SNPs analyzed, the researchers identified FOXO3A as being significantly associated with the long-lived phenotype. Genotype analysis revealed that long-lived study participants had one or more copies of the 'G' allele in the FOXO3A gene. The authors state that this finding is especially exciting because the FOXO family of proteins are closely related to the C. elegans protein, DAF-16, which has been shown to protect cells from oxidative stress, which could be a 'plausible mechanism of action for modification of human aging.'"
A Future of Biogerontechnology (September 15 2008)
Via Emerging Tech: "The US Census Bureau estimates that life expectancy will increase by another six years by 2050. Biogerontechnology, which offers the means to accomplish control over and improvement in the human condition, promises even greater longevity gains. The advancement of the science and technology underlying the biological aging process has the potential to not only extend the average natural lifespan forecasts but also to simultaneously postpone many if not all of the costly and disabling conditions that humans experience in later life, thereby creating a longevity dividend that will be economic, social and medical in nature. The disruptive potential will also come in the form of new treatment modalities, and shifts in the cost, allocation and use of health care resources. Nations will be challenged as a result of the changing demographic structures and new psychologies, behaviors and activity patterns of aging yet healthy citizens and the concomitant need to formulate new national economic and social policies." Less death and less suffering - if only we could all be so "challenged." Hand-wringing over medical progress is ridiculous nonsense at best, and used as the justification for suppression of research at worse.