Longevity Meme Newsletter, February 23 2009

February 23 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.



- Why Are Humans Long-Lived?
- How SIRT1 Works
- Intermittent Fasting Versus Calorie Restriction
- Thoughts on Aging Apologism
- Discussion
- Latest Healthy Life Extension Headlines


We humans are already fairly long-lived in comparison to many of our peer species amongst mammals, though nowhere near as long-lived as we'd like. Here is a look at present thinking on why we have evolved to our present form of longevity, a process that appears to have happened in a similar way in other long-lived mammals, such as killer whales:


"How is it, then, that a woman's lifespan can greatly exceed her childbearing and childrearing years? Is this phenomenon simply a byproduct of improved standards of living, or do older women - grandmothers in particular - play a measurable role in increasing their family members' biological success? ... As it turns out the same questions can be asked of killer whales. They also live long in comparison to many other mammals, far past the age at which they can no longer reproduce."


Researchers have established the mechanism by which the sirtuin SIRT1 operates to provide health benefits. Expression of SIRT1 in the body is boosted by the practice of calorie restriction and use of calorie restriction mimetics like resveratrol, though it seems likely that calorie restriction is doing much more than just manipulating SIRT1 levels, given that CR mimetics are only producing a fraction of the benefits:


"Cells have evolved a particular response to stay alive in adverse conditions. When a cell starts getting too hot, too hungry or too oxygen-deprived, certain proteins migrate into the nucleus. There, they latch onto sections of DNA and cause heat-shock proteins to be produced. Heat-shock proteins - so named because they were first discovered in cells experiencing high temperatures - cruise around the cell, fixing damaged or improperly folded proteins.

"Normally the repair process falls off quickly, because heat-shock proteins inhibit the proteins that grab onto the cell's DNA and summon them in the first place. But Morimoto and his colleagues found that jacking up levels of SIRT1 keeps the protein-repair process going for hours and hours."

Remember: aging is exactly an accumulation of numerous types of unrepaired cellular and molecular damage. More repair is a good thing.


You'll find a discussion on two methods of inducing your body to move into repair mode and boost SIRT1 levels, amongst other benefits:


The bottom line: "Intermittent fasting is usually much easier to introduce into your life, but has far less scientific support or a body of research to indicate the optimum methodology. Calorie restriction requires more initiative to organize, but has a great weight of science backing it up, and a wide range of resources based on decades of practical experience."


The world is packed with well-meaning people who will race to help you survive any threat to your life ... except aging. At the following Fight Aging! post, find some thoughts on the matter from one of the few vocal pro-engineered longevity bioethicists:


"There is almost no end to the reasons people will give to justify why the current rate of aging, and its ever growing disease burden, is actually a good (rather than bad) thing! ... Dawkins has a great line that we are all atheists about most of the gods humans have believed in (thor, zeus, etc.)... some of us just go one god further. Likewise, we are all "pro-longevity" for most things that kill humans (war, cancer, poverty), champions of aging research just go one step further by acknowledging that aging itself is a big problem we should strive to mitigate."


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 Gender Longevity Difference in Humans (February 20 2009)
An interesting paper that opens: "Being male is now the single largest demographic risk factor for early mortality in developed countries ... What causes this disparity between the sexes in longevity and parasite susceptibility? Most research has focused on the proximate mechanisms, such as endocrine or immunological pathways, that are immediately responsible for any one cause. Here, I take a different approach. Sex differences in infection rates or mortality may come about for the same reasons as other differences between males and females, such as morphology: selection acts differently on the sexes because they maximize their fitness in different ways. ... I discuss an evolutionary approach to the question of why males so often die sooner and develop more diseases than females. Some researchers are hopeful that the gap between men's and women's lifespans will close as we develop better medical care and education about health risks, but I will argue instead that the disparity is not going away any time soon." Though it will become negligible as advanced longevity science is put into practice in the decades ahead.

Another Way Alzheimer's Destroys Neurons (February 20 2009)
The end stage of Alzheimer's disease is complex and many-faceted - which is all the more reason to focus on prevention and early repair of the root causes rather than the present strategy of patching the cracks in the dam late in the process: "A protein long suspected as the culprit behind the brain disorder might actually release not just one, but two components that can cause nerve cells to self-destruct. In theory, the breakdown of the protein, called APP for short, could unleash a double whammy of harmful effects on nerve cells. Much of the drug research in the field now focuses on the first component of APP discovered to have a strong link to Alzheimer's disease. That component, the amyloid beta peptide, collects in abnormal plaques in the brain that are a diagnostic sign of the ailment. But a second molecule split off from APP, the N fragment or N-APP, was found to trigger a chain of events that also destroys neurons. ... The question is, how much of the neurodegeneration is triggered by the amyloid beta peptide and how much by N-APP?"

Popular Press on Calorie Restriction (February 19 2009)
A mainstream article on calorie restriction from the Houston Press: "More than 1,000 studies dating back 70 years have shown that eating less, a lot less, retards the aging process and boosts health in a wide variety of laboratory animals: fruit flies, spiders, nematodes, mice, rats, dogs and rhesus monkeys. Calorie-restricted monkeys, for instance, look less wrinkled as they age. They have less gray hair, and look and act younger than their regular-diet counterparts. Eating less seems to make the metabolic processes in the body work more efficiently ... The body enters an altered state that puts the brakes on aging. In mice, flies and monkeys, that is. ... Calorie restriction works in the lower organisms, we know. But with humans it's anybody's guess so far. ... The best guess in the scientific community is that starting a program of calorie restriction in your thirties might add two years ... If you start in your forties, it's six months. Start later than that, it's negligible. It could be a few extra weeks." Longevity benefits are currently thought to be minimal, but the health benefits in humans - in terms of resisting age-related disease, for example - are demonstrated to be large whenever you start.

Arguing Against the Role of Oxidative Stress (February 19 2009)
In this Science Daily release, an unexpected result in worm life span studies is being spun as evidence for oxidative stress not to be important in aging. I believe this is overreaching - it looks much more like a case of one (unexpected) effect that increases life span outweighing the expected effect that decreases life span. These things are never straightforward, however: "For more than 40 years, the prevailing explanation of why we get old has been tied to what is called oxidative stress. This theory postulates that when molecules like free radicals, oxygen ions and peroxides build up in cells, they overwhelm the cells' ability to repair the damage they cause, and the cells age. ... Collectively, these molecules are known as reactive oxygen species, or ROS for short. ... They progressively disabled five genes responsible for producing a group of proteins called superoxide dismutases (SODs), which detoxify one of the main ROS. Earlier studies seemed to show that decreased SOD production shortened an organism's lifespan, but [researchers] did not observe this. In fact, they found quite the opposite. ... It seems that reducing mitochondrial activity by damaging it with ROS will actually make worms live longer."

Aubrey de Grey's Vision (February 18 2009)
The Daily Galaxy outlines Aubrey de Grey's vision for the defeat of aging and age-related disease: "Some people look forward to dying. But de Grey says that's only because we all believe getting old and frail is inevitable - something he refers to as the 'pro-aging trance' society is currently 'trapped' in. De Grey's version of the future is where everyone can stay perpetually healthy and young through a combination of innovative longevity sciences, and he believes it will be more affordable alternative to caring for elderly, frail bodies. He has nothing against old people, he just thinks people should have the option to avoid ageing and death if they want to. There could be other benefits, as well. He says people would welcome eternity if they understood the benefits. ... If we want to hit the high points, number one is, there will not be any frail elderly people. Which means we won't be spending all this unbelievable amount of money keeping all those frail elderly people alive for like one extra year the way we do at the moment. That money will be available to spend on important things like, well, obviously, providing the health care to keep us that way, but that won't be anything like so expensive."

The Future of Regenerative Medicine (February 18 2009)
An overview of what scientists see ahead for regenerative medicine: "Stem cell therapy based on the safe and unlimited self-renewal of human pluripotent stem cells is envisioned for future use in tissue or organ replacement after injury or disease. A gradual decline of regenerative capacity has been documented among the adult stem cell population in some body organs during the aging process. Recent progress in human somatic cell nuclear transfer and inducible pluripotent stem cell technologies has shown that patient-derived nuclei or somatic cells can be reprogrammed in vitro to become pluripotent stem cells, from which the three germ layer lineages can be generated, genetically identical to the recipient. Once differentiation protocols and culture conditions can be defined and optimized, patient-histocompatible pluripotent stem cells could be directed towards virtually every cell type in the human body. Harnessing this capability to enrich for given cells within a developmental lineage, would facilitate the transplantation of organ/tissue-specific adult stem cells or terminally differentiated somatic cells to improve the function of diseased organs or tissues in an individual."

Telomere Length More Complex Than Thought (February 17 2009)
As for everything else in our biochemistry, the shortening of telomeres with age is more complex than we'd like it to be: researchers "have shown that the shortening of telomeres, the protective structures at the end of chromosomes, as people age varies between individuals and depends on the telomeres' original length. Although prior population studies have indicated that telomeres might be used to predict lifespan, the new research shows that the process is in fact much more complicated than had previously been assumed. ... [researchers] investigated the shortening of telomeres in 959 individuals who had donated blood samples at 9- to 11-year intervals. ... while the shortening rate was strongly correlated with the initial length of the telomeres, it was not related to later tumour development. ... In roughly a third of the subjects, the telomeres actually lengthened over the study period. ... those with the longest telomeres at the first blood draw demonstrated the most pronounced telomere shortening over time, and vice versa. ... The results indicate that the telomere-maintenance machinery protects the shortest telomeres. However, other factors are likely to influence the rate of shortening as well. Telomere length at first blood draw could only explain 57% of the variation in the rate of shortening; 43% remains to be accounted for, and may well include lifestyle factors, oxidative stress or inflammation."

Investigating the Mole Rat (February 17 2009)
From Chemistry World, a look at naked mole rats, which "can live for up to 30 years, far longer than the 3 year average life span of a laboratory mouse. ... Traditionally, aging in mammals is attributed to oxidative damage of cells, caused by reaction with inhaled oxygen. ... levels of oxidative stress in young naked mole rats were actually higher than in mice - but that although naked mole rats have high levels of oxidative damage, these stay the same throughout their lifetime. ... In most animals you get an accumulation of oxidative damage with age, but with mole rats, young and old animals have the same protein profile. The mole rats have between two to ten times more oxidative damage in all tissues than mice, and yet they live another 26 years with this damage. ... The rats are able to maintain functionality because they effective mop up damaged proteins in cells. For example, Buffenstein found that, in mice, the liver enzyme GAPDH decreased in activity as the animals aged. However, in naked mole rats, the same enzyme maintained its activity over a 24 year life span. ... Oxidative damage is not the be all and end all of aging. It's rather tolerance to damage and finding ways to cope with those stresses without impacting on functionality that are more important."

Mitochondria Gone Bad (February 16 2009)
Science News surveys the role of accumulating mitochondrial damage and dysfunction in aging and age-related disease: "Today, scientists suspect that millions of people may be suffering from mitochondria gone awry, in more subtle but nonetheless insidious forms. Evidence suggests that malfunctioning mitochondria could explain Alzheimer's disease, Parkinson's, diabetes, cardiovascular disease, obesity, cancer and other consequences of aging. Given the organelle's core function in the body, some think mitochondria might even be the biological epicenter of aging itself: If you live long enough, all your cells might experience a kind of energy crisis. ... I strongly believe that mitochondrial metabolism is the key to aging ... In Mattson's view, and that of other researchers who suspect that people are only as young as their mitochondria, mild amounts of stress force mitochondria to make better use of the glucose available - whether that stress is from calorie restriction or another source. Stress also causes cells to produce proteins that protect the mitochondria from free radical damage. And Mattson points out that other conditions that strain energy production - such as physical and mental activity - also appear to strengthen tissues at the same time."

An Update on Cuervo's Autophagy Research (February 16 2009)
You might recall the research by Cuervo's group demonstrating a restoration of youthful levels of autophagy in mouse livers. We know that autophagy is important to longevity: it clears out biochemical junk and damaged cellular components, of which the most important are probably damaged mitochondria. Furthermore, autophagy is enhanced by calorie restriction, and appears necessary for the longevity benefits of calorie restriction to take place. The most interesting tidbit from this ABC News article is that it looks like Cuervo's method of restoring autophagy levels does in fact increase life span (as measured by survival rates at various ages) in mice: "In experiments, livers in genetically modified mice 22 to 26 months old, the equivalent of octogenarians in human years, cleaned blood as efficiently as those in animals a quarter their age. By contrast, the livers of normal mice in a control group began to fail. ... While her paper does not show increased survival rates among the mice, le Couteur, who has advised her recently on the research, says Cuervo does have data on improved survival rates which she intends to publish. He also says she is now working with pharmaceutical companies to identify drugs that will turn the receptors on, or make them more active. Cuervo believes maintaining efficient protein clearance may improve longevity and function in all the body's tissues."



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