Longevity Meme Newsletter, September 07 2009

September 07 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.



- Early Coverage of the SENS4 Conference
- There is No Overpopulation
- Immune System Rejuvenation Through Destruction
- Discussion
- Latest Healthy Life Extension Headlines


The 4th Strategies for Engineered Negligible Senescence conference is nearing its close, one of the few respectable scientific conference series devoted to longevity science and the repair of age-related biochemical damage. Some coverage of the first two days from aging science blog Ouroboros can be found linked at this Fight Aging! post:


Earlier last week, I'd commented on the presentation to be given by Vladimir Skulachev. His research group has developed and demonstrated a form of ingested mitochondrially targeted antioxidant:


"Skulachev's laboratory has demonstrated a 30% healthy life extension in mice through this methodology, while US research groups have used the naturally produced antioxidant catalase and gene engineering to achieve much the same sort of end result: antioxidants localized to mitochondria, and extension of healthy life in mice."

Note that all other known forms and applications of antioxidants have negligible consequences on mouse life span. The balance of evidence at the moment suggests that targeting mitochondria, the cell's power plants, is the important factor. Mitochondria are generators of damaging free radicals (that antioxidants can soak up), but are also the most vulnerable target in the cell - an unfortunate combination. You can soak everything other than mitochondria in antioxidants, but it won't do much, because all the action is happening inside the mitochondria.

You might look back in the Fight Aging! archives for an explanation of the mitochondrial free radical theory of aging, and a more detailed breakdown as to why directing antioxidants to mitochondria is effective while every other antioxidant strategy attempted to date does little for life span:



Some thoughts on overpopulation and support for longevity research, prompted by a recent SENS Foundation funded demographic projection study, can be found at the following link:


"By far and away the most common reason I see given these days in opposition to engineered longevity is fear of overpopulation. Environmentalism has become almost a religion in its own right now, and many strands of that religion are essentially death cults: loose networks of like-thinking people who fervently believe, for whatever reasons, that the world is dying, that humans already live too long, and that people should be forced to relinquish technology and return to a simpler era. Extreme fringe variants of the environmentalist death cult really do stand for the complete destruction of humanity, but even supposedly reasonable, middle of the road people are influenced by deathist environmentalism to the point at which it is seen as reasonable to say that (a) too many people exist, and therefore (b) the unending horror, pain, and suffering of death by aging is necessary.

"Death cult environmentalism of the 'too many people' variety is, fundamentally, a failure of understanding. It is to look at the undeniably bad situations and unpleasant regions of the world and say 'this is because too many people are using too many resources,' rather than to see that in fact it's all due to misallocation of existing resources and the failure to develop new resources - a grand procession of waste, corruption, and the inhumanity with which human beings treat one another. These situations are problems that can be solved through development and tearing down corrupt systems of rulership - they are not immutable facts of life that must lead to the deaths of millions."


It seems plausible that important facets of age-related immune system degeneration could be reversed by selectively destroying some immune cells:


"One of the reasons that the immune system degenerates with age is, and I greatly simplify the reality on the ground in saying this, that only a limited number of immune cells can be supported at once. As the years roll on more and more of the immune cells known as T cells become memory T cells, dedicated to remembering specific threats. That leaves less and less room for naive T cells that can go out and stomp on new threats. Thus as your immune system becomes ever more knowledgeable, it also becomes less and less effective at its primary missions - including destroying pathogens, destroying senescent cells, and destroying early stage cancers.

"Now in theory, an old immune system that is top-heavy in memory T cells could be at least partially restored (remember that there are other issues and degenerations beyond the one I discuss here) by destroying all the unwanted memory cells. In recent years researchers have destroyed and then used stem cells to recreate the entire immune system in human trial patients, and have done this to essentially remove misconfigured immune cells that were the source of an autoimmune disorder. If that can be done, then it should certainly to be possible to take one of the new generation of targeted cell destruction technologies developed in the cancer research community and use to it destroy only a specific population of T cells."


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!




What can be achieved through manipulation of skin stem cells? Quite a lot, it seems, and by virtue of its accessibility we might expect to see important techniques first pioneered in skin regeneration: "Recent advances in skin-resident [progenitor cell] research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. ... enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging may induce severe DNA damages and genomic instability in the skin-resident [progenitor cells] and their progenies. ... The progressive decline in the regenerative functions and/or number of skin-resident [progenitor cells] may cause diverse skin diseases with advancing age. Moreover, the photoaging, telomerase re-activation and occurrence of different oncogenic events in skin-resident [progenitor cells] may also culminate in their malignant transformation into [cancer stem cells] and skin cancer initiation and progression. Therefore, the anti-inflammatory and anti-oxidant treatments and stem cell-replacement and gene therapies as well as the molecular targeting of their malignant counterpart, skin cancer-initiating cells offer great promise to treat diverse skin disorders and cancers."

Here is another review paper examining the (strong) evidence for the central role of autophagy in the way in which metabolism determines natural longevity: "The accumulation of cellular damage is a feature common to all aging cells and leads to decreased ability of the organism to survive. The overall rate at which damage accumulates is influenced by conserved metabolic factors (longevity pathways and regulatory proteins) that control lifespan through adjusting mechanisms for maintenance and repair. Autophagy, the major catabolic process of eukaryotic cells that degrades and recycles damaged macromolecules and organelles, is implicated in aging and in the incidence of diverse age-related pathologies. Recent evidence has revealed that autophagic activity is required for lifespan extension in various long-lived mutant organisms, and that numerous autophagy-related genes or proteins are directly regulated by longevity pathways. These findings support the emerging view that autophagy is a central regulatory mechanism for aging in diverse eukaryotic species."

Another good reason to keep up with exercise: "Age is the major risk factor for cardiovascular diseases (CVD) and this is attributable in part to stiffening of large elastic arteries and development of vascular endothelial dysfunction (e.g., impaired endothelium-dependent dilation, EDD). In contrast, regular aerobic exercise is associated with reduced risk of CVD. Endurance exercise-trained middle-aged/older adults demonstrate lower large elastic artery stiffness and greater EDD than their sedentary peers. With daily brisk walking, previously sedentary middle-aged/older adults show reduced stiffness and improved EDD. The mechanisms underlying the effects of regular aerobic exercise on large elastic artery stiffness with aging are largely unknown, but likely include changes to the composition of the arterial wall. Enhanced EDD in older adults who exercise is mediated by increased nitric oxide (NO) bioavailability associated with reduced oxidative stress. Arteries from old rodents that undergo aerobic exercise training demonstrate increased expression and activity of endothelial NO synthase, reduced oxidative damage associated with reduced expression and activity of the oxidant enzyme NADPH oxidase, and increased activity of the antioxidant enzyme superoxide dismutase. Aerobic exercise also may protect arteries with aging by increasing resistance to the effects of other CVD risk factors like LDL-cholesterol. Habitual aerobic exercise is an effective strategy to combat arterial aging."

Thoughts from Anne C.: "however you do it, the important thing is to get your brain geared up to more accurately assess reality, and the claims people make about it. See, there are plenty of hucksters out there who would probably be more than willing to sell you their Super-Longevity Bio-Kit or some other quackish nostrum. And despite not being a biologist myself, I think I'm at least informed enough on the subject of biogerontology to be able to tell you that anyone who claims to have the 'path to immortality' is either deluded or lying. Hence, taking people who make such claims seriously is likely to be a waste of time for everyone involved, and obviously over time this kind of thing is likely to lead to less actual useful real-world work [on engineered longevity] being done. ... Here in the real world, the best any of us can do if we want longer, healthier lives for our loved ones and ourselves is contribute toward actual real-world things that promote health, life, and solid research. And in order to figure out what projects are valid and worth supporting, or worth proposing and starting ourselves, critical thinking is utterly essential."

WHO WANTS TO LIVE FOREVER? (September 02 2009)
From Vision: "That our allotted time on this earth is somewhat fleeting has surely not escaped us, especially as we move farther down our life path. ... In recent years, however, a building revolution in the science of gerontology has heralded the possibility of life extension. This is leading some to speculate about just what the limits to human life might be; adding another decade or two or even centuries might be possible. ... As our knowledge of the biochemistry of aging increases exponentially, it is no surprise that around the globe scientists are discovering hopeful paths that will provide ways to increase human longevity. Meanwhile, biotechnology companies are seeking to bring new products to market - drugs, cells, tissues, and procedures - which they, too, hope will go some way toward extending life as well as bring a profit. ... Is death therefore in terminal decline? While the commercial and media hype concerning such a possibility has dismayed some mainstream scientists, others such as Aubrey de Grey have spearheaded efforts to, as he puts it, 'cure the disease of aging.' The [SENS Foundation] chairman and biogerontology researcher is not only chasing the dream of immortality; he expects to catch it."

ALCOR EMAIL NEWSLETTER (September 02 2009)
Cryonics provider Alcor has an email newsletter that you might consider signing up for if you'd like to learn more about how cryonics works and the concerns and day to day operations of a provider. For example: "Several outreach initiatives are underway. It has been established that a primary source of membership growth is referral by existing Alcor members, so several board directors have begun proactively contacting prospective members. These communications have the side benefit of offering constructive feedback that will help improve the organization. For instance, one of the individuals informed us that the subscription process for Alcor News was not functioning properly. The malfunction has now been resolved. Another outreach initiative is the formation of a Communications Committee, also composed largely of board directors. Among other endeavors, committee members will participate in screening or soliciting media opportunities and live speaking engagements, identifying appropriate speakers, developing talking points and encouraging media training."

While sirtuins extend life in lower animals, manipulation of sirtuins in mammals hasn't produced the sort of enhanced longevity seen in other genetic engineering techniques, or even just plain old calorie restriction. Here, a reason is suggested: "Sir2 mediates lifespan extension in lower eukaryotes but whether its mammalian homolog, SIRT1, is a longevity protein is controversial. We stably introduced the SIRT1 gene into human vascular smooth muscle cells (SMCs) and observed minimal extension of replicative lifespan. However, SIRT1 activity was found to be exquisitely dependent on nicotinamide phosphoribosyltransferase (Nampt) activity. Moreover, overexpression of Nampt converted SIRT1-overexpressing SMCs to senescence-resistant cells [with] strikingly lengthened replicative lifespan. Thus, SIRT1 can markedly postpone SMC senescence, but this requires overcoming otherwise vulnerable NAD(+) salvage in aging SMCs." With the caution that results in cells are not results in whole animals, you might want to take a look at the role of NAD+ in cells. It is part of a cycling mechanism of metabolism that can cause all sorts of issues if disrupted.

At least some cases of Parkinson's disease are spurred on by mitochondrial failure: "Parkinson's disease is caused by the degeneration of neurons in the midbrain. The mechanisms leading to the loss of these neurons, however, are largely unknown. Recent research revealed that about ten per cent of cases are caused by defects in so-called Parkinson-associated genes. Furthermore, mitochondria, the cellular powerhouses, seem to play a major role. New results [connect] both phenomena, showing that two Parkinson genes maintain the function of mitochondria. ... Functionally impaired mitochondria have been recognized to trigger Parkinson's disease already in the early eighties ... The relevance of mitochondria to the loss of neurons seems plausible - after all, mitochondria supply the cells with energy in form of adenosine triphosphate and play a substantial role in the regulation of cell death. ... Parkinson-associated genes PINK1 and Parkin functionally interact to maintain mitochondrial function. Loss of Parkin or PINK1 function impairs the morphology and activity of mitochondria, which then produce less adenosine triphosphate."

The biochemistry of the heat shock response is connected with enhanced cellular housekeeping and repair, here demonstrated again in nematode worms: "Exposure to mild heat-stress (heat-shock) can significantly increase the life expectancy of the nematode Caenorhabditis elegans. A single heat-shock early in life extends longevity by 20% or more and affects life-long mortality by decreasing initial mortality only; the rate of increase in subsequent mortality (Gompertz component) is unchanged. Repeated mild heat-shocks throughout life have a larger effect on life span than does a single heat-shock early in life. Here, we ask how multiple heat-shocks affect the mortality trajectory in nematodes and find increases of life expectancy of close to 50% and of maximum longevity as well. We examined mortality using large numbers of animals and found that multiple heat-shocks not only decrease initial mortality, but also slow the Gompertz rate of increase in mortality. Thus, multiple heat-shocks have anti-aging hormetic effects and represent an effective approach for modulating aging."

SENS4, the 4th Strategies for Engineered Negligible Senescence conference, is almost upon us: "The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - to reverse - those changes, rather than merely to slow down their further accumulation." Let me direct your attention to the long list of abstracts for presentation; you'll find a lot of very interesting research in there. For example, the Gavrilovs' examination of demographic changes likely to result from the slowing or reversal of aging: "A common objection against starting a large-scale biomedical war on aging is the fear of catastrophic population consequences (overpopulation). This fear is only exacerbated by the fact that no detailed demographic projections for radical life extension scenario were conducted so far. What would happen with population numbers if aging-related deaths are significantly postponed or even eliminated? Is it possible to have a sustainable population dynamics in a future hypothetical non-aging society? This study explores different demographic scenarios and population projections, in order to clarify what could be the demographic consequences of a successful biomedical war on aging."



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