Longevity Meme Newsletter, March 29 2010

March 29 2010

The Longevity Meme Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to the Longevity Meme.



- Wealth and Longevity
- The Mainstream Scientific Consensus on Aging
- The Methuselah Foundation's Present Strategy
- Aging and the Innate Immune System
- Discussion
- Latest Healthy Life Extension Headlines


The wealth of a region and the longevity of its inhabitants go hand in hand: history presents a convincing case that increases in one lead to increases in the other.


"The societal and economic changes wrought across the 17th century in England, for example, show us that increased longevity leads to increased wealth, through more foresighted allocation of capital resources and the compounded effect of small gains, year after year. The converse is also true: increased wealth leads to increased longevity, a fact well illustrated by the passage of many Asian countries from undeveloped to developed in a short span of decades. Let us take the economic history of South Korea, for example, which had one of the world's fastest growing economies from the early 1960s to the late 1990s. Across this same period of time, life expectancy in South Korea rose dramatically."


The mainstream of the aging research community focuses on slowing aging through manipulation of metabolism or general improvements in medical technology, and its members sadly give little thought to initiatives like the Strategies for Engineered Negligible Senescence, aimed at reversing the damage that causes aging. If you'd like to read a fairly concise outline of the mainstream view, you should look at the latest issue of Nature Insight. It is presently open access, and the papers are linked from the Fight Aging! post below:


"It is now clear that by tinkering with particular signalling pathways and by balancing nutrition, the lifespan of many organisms, including yeast, worms, flies and mice, can be extended. Crucially, the same tweaks often bring about substantial health benefits and seem to delay the onset of age-related diseases. Most of the pathways involved are evolutionarily conserved, so it is likely that some of this research will eventually benefit human health.

"The finding that mortality at advanced ages can be postponed, and indeed is being postponed, resolved a millennia-old debate about whether survival could be extended among the elderly. The evidence published since 1994 is compelling. Unless radical breakthroughs are achieved, perhaps as a result of research on other species, humans will continue to suffer senescence - but the process is not intractable. Mortality has been postponed considerably, as a result not of revolutionary advances in slowing the process of ageing but of ongoing progress in improving health."


A recent announcement from the Methuselah Foundation sheds more light on their present strategy aimed at broadening the community of those who support engineered longevity:


"Those of us who are already enthusiastic about the idea of science to help us life much longer are comparatively rare outliers: we tend to understand how technology can change the world around us, and feel comfortable estimating the plausibility of future technologies based on present trends and capabilities. But most people live in the here and now: it's hard to persuade them that the future will be far different from what they see today. Yet these folk make up the majority of the population, and until we can persuade them to see things our way, the quest to extend the healthy human life span will remain a fringe interest. We need the enthusiasm and help of the masses to support the pace and breadth of progress we'd like to see.

"One of the ways in which the Methuselah Foundation is approaching this problem is funding for cutting edge regenerative medicine, such as organ growth. These are more widely supported and understood technologies, and making the Foundation a player in this space will help to put the message of engineered longevity in front of more people, and in a way they are more likely to sympathize with and understand."


Your immune system has two major active components of interest. Firstly, the innate immune system responds quickly and in the same way to all new threats. Its job is to kill what it can, and while doing that trigger activation of the second component, the adaptive immune system. The adaptive component of the immune system, unlike the innate component, remembers threats and alters itself to better defend against them in the future. Most of the past discussions on immune system aging and what to do about it at Fight Aging! have focused on the adaptive component, which fails rather dramatically in later life, and for reasons that seem to be both preventable and reversible. See this post, for example:


The innate component of the immune system also changes for the worse with aging, however. The good news is that this seems to be something that could in principle be repaired, although at the present time far less is known of the mechanisms involved:


"Recent literature suggests that, in advanced age, phagocytes [of the innate immune system] undergo significant changes in signal transduction pathways that may affect their ability to perform antimicrobial functions or regulate the inflammatory response. These abnormalities are expected to contribute to the pathology of oral infection-driven inflammatory diseases in the elderly. Moreover, the elucidation of age-associated defects in the innate immune system will facilitate the development of intervention therapeutic strategies to promote or restore innate immune function and improve the quality of health in old age."


The highlights and headlines from the past week follow below.

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From ScienceDaily: "scientists transplanted embryonic neurons from fetal rats into an area of the adult rat brain known as the striatum, which integrates excitatory and inhibitory neurotransmitter signals to control movement. In Parkinson's disease, cells that produce the neurotransmitter dopamine are damaged, and thus unable to project their communication wires, or axons, to the region. As a result, the balance of excitation and inhibition in the striatum is lost, causing the motor deficits that are a primary symptom of the disease. ... the transplanted embryonic neurons migrated and integrated into the correct neural circuitry of the striatum, matured into so-called GABAergic inhibitory interneurons, and dampened the over-excitation in the region. The rats had improved motor function, as seen in their balance, speed, and length of stride during walking. Moreover, the healthy 'control' rats in which the cells had been transplanted took longer strides and ran faster on a runway test." This won't be the last time that transplant of fetal or embryonic cells shows benefits in normal recipients as well as those suffering from disease - all the more reason to understand how to reprogam adult cells to look more like fetal cells.

As researchers learn more of the mechanisms of the immune system, they will be able to selectively reprogram its components - and thus cure many of the conditions that result from immune system malfunctions. From EurekAlert!: "immune system components known as regulatory T cells counterbalance the tendency of conventional T cells to become overactive, thus holding inflammation in check. These regulatory T cells exert their influence by communicating with other parts of the immune system. ... an enzyme known as protein kinase C theta is only partly activated in regulatory T cells. When the regulatory cells are most active, in fact, most of the interfering enzyme is physically kept far away from the area important for cell-cell communication. ... researchers began testing inhibitors of this kinase enzyme, including a molecule known as Compound 20 ... the compound boosted the normal activity of regulatory T cells by about five-fold [and] defective regulatory cells from [patients] were revived in tissue cultures with this enzyme inhibitor ... We could get them back to almost a normal level of activity, like what you'd see in a healthy individual. ... When the researchers treated the regulatory T cells with the enzyme inhibitor and then injected them into the mice [with the mouse version of Crohn's disease], their anti-inflammation activity rose so much that they essentially protected the mice from the disease, even though the cells were outnumbered four to one by their pro-inflammatory counterparts."

A Forbes columnist points out the insanity of the FDA regulations that block any consideration of treating aging: "For the most part, the FDA still operates under the medical mind-set that prevailed when the federal drug law was amended in 1962. The go/no-go regulatory calls are decided by clinical trials. The key metrics are clinical, like the survival time for a cancer patient. A clear reduction in mortality from a serious disease gets the drug licensed on the double. So far, so good - this panel sounds diligently antideath. But it's interested only in brinkmanship, at the back end. The 'aging' drugs that the FDA deals with reasonably well are the ones that beat back a single specific disease long after the microscopic seeds of the problem have blossomed into big symptoms. Aging is an incremental, whole-body problem. All cells, tissues and organs age - and in different ways, at different rates, in different people. As defined by their late-stage clinical symptoms, the diseases of old age are legion. At the FDA they will have to be beaten one at a time or not at all. Which means that nobody is ever going to get 'antiaging' drugs through the FDA as it currently operates. Certainly not drugs that operate the way [biomedical gerontologist Aubrey de Grey] suggests they might, by repairing damage at the cellular level before it morphs into clinical problems."

Researchers continue to delve into the details of regeneration in lower animals: "Bony fish like the tiny zebrafish have a remarkable ability that mammals can only dream of: if you lop off a chunk of their heart they swim sluggishly for a few days but within a month appear perfectly normal. How they accomplish this - or, more importantly, why we can't - is one of the significant questions in regenerative medicine today. .. [Researchers have] identified a fish heart cell population that is the source of this astonishing healing feat ... well established cardiomyocytes remaining after injury had likely regressed to a more 'youthful' state, started dividing again to replenish lost cells, and then matured a second time into new heart muscle. The group also showed cardiomyocytes recaptured lost youth in part by re-activating the production of proteins associated with cell proliferation, factors typically expressed in immature progenitors. Human hearts cannot undergo these types of regenerative changes on their own. When damaged by heart attack, our heart muscle is replaced by scar tissue incapable of contracting. However, prior to heart failure, damaged mammalian heart muscle cells enter a save-yourself state known as 'hibernation,' in which they cease contracting in an effort to survive. ... During heart regeneration in the zebrafish we found that cardiomyocytes displayed structural changes similar to those observed in hibernating cardiomyocytes. Because of these similarities, we hypothesize that hibernating mammalian cardiomyocytes may represent cells that are attempting to proliferate."

From Reason Magazine, a look at where the economics of medical research and development are heading, thanks to the ever-increasing adverse effects of regulation: "At the beginning of the last decade, there was great excitement about the future of medicine. Advances in biotechnology, nanotechnology, diagnostics, information technology, stem cell treatments, vaccines, and organ transplants were poised to radically improve the health prospects of Americans. Looking back from 2020, we can see that most of these major biomedical advances failed to materialize. What happened? Three words: health care reform. ... Big pharmaceutical companies initially did fairly well under health care reform, but as the cost of health care rose partly as a result of covering more Americans, Congress enacted legislation allowing government health care schemes to 'negotiate' pharmaceutical prices. The negotiation requirement quickly devolved into price controls that have ultimately turned the big drugmakers into little more than cost-plus government contractors. In addition, the feds have established a comparative effectiveness evaluation commission similar to the British National Institute for Health and Clinical Excellence which limits patient access to treatments based on their overall cost-effectiveness. The result of these restrictions is that investments in pharmaceutical and biotech research and development have fallen off sharply. ... The seen aspect of health care reform is that it has had some success in providing more Americans with access to vintage 2010 medical therapies. The unseen aspect is that more people are suffering from and dying of diseases that might well have been cured."

Via PhysOrg.com: researchers have found "elderly people with super-sharp memory - so-called 'super-aged' individuals - who somehow escaped formation of brain 'tangles.' The tangles consist of an abnormal form of a protein called 'tau' that damages and eventually kills nerve cells. Named for their snarled, knotted appearance under a microscope, tangles increase with advancing age and peak in people with Alzheimer's disease. ... its implications are vast. We always assumed that the accumulation of tangles is a progressive phenomenon throughout the normal aging process. Healthy people develop moderate numbers of tangles, with the most severe cases linked to Alzheimer's disease. But now we have evidence that some individuals are immune to tangle formation. The evidence also supports the notion that the presence of tangles may influence cognitive performance. Individuals with the fewest tangles perform at superior levels. Those with more appear to be normal for their age. ... One group of super-aged seems to dodge tangle formation. Their brains are virtually clean, which doesn't happen in normal-aged individuals. The other group seems to get tangles but it's less than or equal to the amount in the normal elderly. But for some reason, they seem to be protected against its effects."

Via EurekAlert!, an estimate of the cost of poor lifestyle choices: "A new study [estimates] that smoking, high blood pressure, elevated blood glucose and overweight and obesity currently reduce life expectancy in the U.S. by 4.9 years in men and 4.1 years in women. It is the first study to look at the effects of those four preventable risk factors on life expectancy in the whole nation. ... Smoking, high blood pressure, elevated blood glucose and obesity are responsible for hundreds of thousands of deaths from chronic diseases such as cardiovascular diseases, cancers and diabetes, in the U.S. each year. ... For their study, the researchers used 2005 data from the National Center for Health Statistics, the National Health and Nutrition Examination Survey, the Behavioral Risk Factor Surveillance System, and an extensive review of epidemiologic studies on the effects of these factors. They estimated the number of deaths that would have been prevented in 2005 if exposure to the four risk factors had been reduced to their optimal levels or commonly used guidelines. They also assessed the benefits for life expectancy, a measure of longevity. ... As a result of these patterns, smoking, high blood pressure, elevated blood glucose and overweight and obesity account for almost 20% of disparities in life expectancy across the U.S. These four factors also accounted for three quarters of disparities in cardiovascular mortality and up to half of disparities in cancer mortality."

From the Jerusalem Post: "researchers have discovered that pregnancy has the remarkable ability to promote the regeneration in elderly mice of damaged livers and muscles. They have also managed to mimic the state of pregnancy using specific molecules that trigger the regeneration and growth of livers in older rodents. This basic new concept [could] eventually be relevant to other tissues and organs and lead to the ability to stimulate their regeneration in elderly, sick patients. ... [Earlier researchers] had connected young mice to other young mice by uniting their blood vessels; old mice to old mice; and young mice to old mice (this procedure is called parabiosis). ... pregnancy was a kind of parabiosis in which a mother is connected by blood vessels to its young fetus. ... The team studied mice and indeed found that damage to tissue in the foot muscle (and later liver) of an older but pregnant mouse was quickly repaired, as if it had been connected to a live young animal. ... pregnancy causes a switch from regeneration based on proliferation (an increase in the number of cells due to cell division) to regeneration caused by hypertrophy (the increase in the volume of an organ or tissue due to the enlargement of its component cells). Certain molecules given to aged mice induced hypertrophy in their livers, thus mimicking the state of pregnancy and lengthening their lifespan."

The various known accelerated aging conditions can teach us about the mechanisms of normal aging. Here, USA Today looks at Down syndrome in this context: "People with Down syndrome tend to age prematurely as they develop conditions such as menopause, brittle bones, arthritis, hearing loss, wrinkles and sagging skin about two decades earlier than usual ... Yet researchers suspect that this unique genetic profile also protects people with Down syndrome from many common ailments. ... most adults with Down syndrome are overweight with high cholesterol. Despite these risks, however, people with Down syndrome virtually never develop high blood pressure, heart attacks or hardening of the arteries ... with the exception of a rare pediatric leukemia, even elderly adults with Down syndrome rarely develop solid tumors, such as those of the breast or lung. ... Although people with Down syndrome are at higher risk for cataracts, they rarely develop a form of blindness called macular degeneration, caused by an overgrowth of blood vessels in the retina ... Doctors suspect that the same genes [duplicated in Down syndrome] that restrict blood vessel growth in tumors may also prevent abnormal blood vessel growth in the eye. ... Adults with Down syndrome appear to develop the brain plaques and tangles characteristic of Alzheimer's disease very early in life ... By age 40 to 45, virtually everyone with Down syndrome has these plaques and tangles, [and by] age 65, up to 75% of people with Down syndrome have dementia."

The the Technology Review: "A specialized nanoparticle filled with an RNA-based cancer therapy can successfully target human cancer cells and silence the target gene, according to results from an early clinical trial. The research [is] the first to demonstrate this type of tissue targeting and gene-silencing in humans. ... Since the discovery 12 years ago that double-stranded RNA can silence genes in a targeted manner, researchers have hailed the technique, known as RNA interference (RNAi), as a powerful approach to creating new and potent medicines. ... The trouble is, getting the therapeutic RNA to the right cells has proven to be a sticky challenge. When injected on their own, so-called small interfering RNAs (siRNAs) are quickly filtered out by the kidneys, and researchers have struggled to design particles that carry their contents to target cells with enough specificity, or that don't cause toxicity or elicit an immune reaction from the body. ... The new trial [is] the first to administer the RNA therapy systemically into the body, using specialized particles that protect the RNA while in the bloodstream and target it directly to cancer cells. ... The researchers analyzed biopsy samples from three melanoma patients in the trial who had received different doses of the therapy. They tracked the particles in the different samples, finding that the amounts they could see in the tumor cells correlated with the doses the patients received."



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