Fight Aging!

LONGEVITY MEME NEWSLETTER
March 17 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.

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CONTENTS

- Byproducts, Gunk and Age-Related Blindness
- The Death of "Anti-Aging"
- Discussion
- Latest Healthy Life Extension Headlines

BYPRODUCTS, GUNK AND AGE-RELATED BLINDNESS

One characteristic difference between young tissue and aged tissue is the accumulation of metabolic byproducts and other forms of biochemical gunk that the body cannot break down, or can no longer break down rapidly enough. Better known amongst these damaging compounds are advanced glycation endproducts (AGEs), formed when sugars glom onto vital biomolecules, and lipofuscin, a catch-all term for a mix of many different types of chemical that the cell cannot break down.

As it happens, researchers working on the mechanisms of age-related blindness are a touch further ahead than others when it comes to understanding exactly how the buildup of AGEs and lipofuscin damages tissue. For example, the component of lipofuscin called A2E seems to enhance errant blood vessel growth in the retina that is characteristic of wet macular degeneration:

https://www.fightaging.org/archives/001434.php

"Toxic constituents of lipofuscin are generated as byproducts of the visual cycle, a complex chemical pathway that is required for the maintenance of the light gathering components of the eye called retinal photoreceptors. ... results suggest that A2E accumulation results in the phenotypic alteration of retinal pigment epithelial cells, predisposing the environment to [errant blood vessel] development."

Meanwhile, AGEs seem to cause damage in the eye by overwhelming the cellular receptor known as RAGE. Receptors might be thought of as input devices for cells - when a receptor is hit with the right sort of molecule, cellular machinery will then undertake a specific set of actions. The accumulation of AGEs adds constant mistyping to the keyboard of cellular communication, instructing cells to take actions that damage their environment and function:

https://www.fightaging.org/archives/001435.php

"While the understanding of RAGE and its role in retinal dysfunction with aging, diabetes mellitus, and/or activation of pro-inflammatory pathways is less complete compared to other organ systems, increasing evidence indicates that RAGE can initiate and sustain significant cellular perturbations in the inner and outer retina."

The solution to age-related degenerations caused by lipofuscin and AGEs - of which blindness is just one of many - is to remove enough of these damaging compounds, through drugs, bacterial enzymes or other methodologies, to keep them below the level at which damage occurs. Sadly, research initiatives in this direction, such as those funded by the Methuselah Foundation or Legendary Pharmaceuticals, are still a drop in the bucket of what the medical research industry spends to find ways to briefly and partially patch the end results.

As is so often the case, the solution to our problems is as much to change the emphasis of the research community as it is to find the best technical path forward:

https://www.fightaging.org/archives/000850.php
https://www.fightaging.org/archives/000936.php

THE DEATH OF "ANTI-AGING"

Some thoughts on the term "anti-aging":

https://www.fightaging.org/archives/001436.php

"You need a bigger foghorn to compete with the folk presently engaged in efforts to define 'anti-aging,' either implicitly or explicitly. The term has solidly come to mean Revlon, skin cream, potions and the art of patching over the cracks so as to look younger, while doing absolutely nothing about the damage of aging. The forgery of the mirror and makeup, the magic show in which we expect to be entertained while understanding that none of it is real.

"The hundreds of thousands (millions?) of devoted purchasers of useless 'anti-aging' products translates into very, very few people who understand and give support to serious attempts to repair the damage of aging through modern science. We advocates for longevity science may as well direct our educational and awareness efforts to the population at large - there is no special leverage to be had in speaking to Revlon customers. If there was, we'd have seen it already."

DISCUSSION

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!

Reason

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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/

Immortality Institute Redesign (March 14 2008)
http://www.imminst.org
If you haven't visited the Immortality Institute recently, you should head on over and take a look. The latest redesign is up, intended to better focus visitors on the Institute mission, as well as to present the latest science of longevity and aging and happenings in the healthy life extension community. As always, you'll find an interesting mix of folk in the Institute forums, still a watering hole for people from across the range of the community. Recent functional additions include a wiki for FAQs and other documents: "The Immortality Institute is a non-profit organization with the goal of defeating the disease we call aging. Our official mission is 'to conquer the blight of involuntary death.' We think that this has the possibility of being accomplished through a variety of means, some more radical than others. We try to further the goal of defeating aging through a variety of means, including debate and discussion [amongst] scientists and researchers in the various anti-aging related fields, the production of various informational materials (films, books, etc.), the hosting of conferences dedicated solely to various aspects about the war on aging, funding of research related to curing aging, and many other ways that we think will provide the most benefit to curing aging as quickly as possible."

Incoherent Immortality (March 14 2008)
http://www.existenceiswonderful.com/2008/03/longevity-is-lovely-but-immortality-is.html
Immortality is a much abused word, often used in the healthy life extension community as shorthand for physical immortality, the state of not suffering from degenerative aging - being well repaired on a regular basis by use of future medical technologies, in other words. Anne C. has some thoughts: "I don't see longevity advocacy, or longevity medicine, as having anything to do with Infinite Invulnerable Indestructuble-ness or any other metaphysical fantasy. No matter what amazing medical technologies are developed, there's never going to be any guarantee that any person exists in a state wherein continued existence forever is somehow assured. ... In other words, when I talk about life being wonderful, and about the necessity of making medicine as effective as possible for old people as well as for young people - in fact, even when I talk about the notion of mitigating things presently considered 'part of the aging process' - I am not talking about 'making people immortal'. Just, you know, in case that wasn't clear."

Fat, Inflammation and Atherosclerosis (March 13 2008)
http://www.eurekalert.org/pub_releases/2008-03/uorm-sic031308.php
Not to hammer on the point too much, but excess body fat held over the years causes chronic inflammation, which enrages your immune system, which leads to atherosclerosis, which tends to kill you abruptly and without warning. All very avoidable. To make matters worse, excess fat - or rather all the food you ate in order to create the excess fat - creates a feedback mechanism that leads to insulin resistance and diabetes, and this makes the atherosclerosis-generation process run faster: "Experts once believed that atherosclerosis, or hardening of the arteries, developed when too much cholesterol clogged arteries with fatty deposits called plaques. When blood vessels became completely blocked, heart attacks and strokes occurred. Today most agree that the reaction of the body's immune system to fatty build-up, more than the build-up itself, creates heart attack risk. Immune cells traveling with the blood mistake fatty deposits for intruders, akin to bacteria, home in on them, and attack. This causes inflammation that makes plaques more likely to swell, rupture and cut off blood flow. ... In part because diabetes increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke. ... Inflammation is blood vessels is one of the main drivers of atherosclerosis, and diabetes makes it much worse."

Conservation of Longevity Genes (March 13 2008)
http://www.eurekalert.org/pub_releases/2008-03/uow-sin031108.php
Some core components of metabolism - and, by extension, the rate at which that metabolism damages itself into aging - are very ancient, changing comparatively little as species evolved radically. That's why gerontologists focused on metabolism can obtain useful data from animals as diverse as zebrafish, flies, mice and primates. From EurekAlert!: researcher "have identified 25 genes regulating lifespan in two organisms separated by about 1.5 billion years in evolutionary change. At least 15 of those genes have very similar versions in humans ... Several of the genes that the scientists identified as being involved in aging are also connected to a key nutrient response pathway known as known as the Target of Rapamycin, or TOR. That finding gives more evidence to the theory that calorie intake and nutrient response affect lifespan by altering TOR activity. ... To find these lifespan-controlling genes, the scientists took a genomic approach to comprehensively examine genes that affect aging in yeast and worms. Based on published reports, they first identified 276 genes in C. elegans that affected aging, and then searched for similar genetic sequences in the yeast genome. Of the 25 aging-related genes they found in both worms and yeast, only three had been previously thought to be conserved across many organisms."

Exploring the Biochemistry of Progeria (March 12 2008)
http://pmid.us/18331619
Is seems to be the case that the accelerated aging of progeria (HGPS) results from one minor component of "normal" aging run wild - the defects resulting from mutant lamin A. So it is plausible that therapies for progeria will have some value for the rest of us in due time. It is worth paying attention to the research: "Lamins are essential to maintain nuclear integrity and loss of lamin A/C results in increased cellular sensitivity to mechanical strain ... We found that skin fibroblasts from HGPS patients developed progressively stiffer nuclei ... fibroblasts from HGPS patients had decreased viability and increased apoptosis under repetitive mechanical strain, as well as attenuated wound healing, and these defects preceded changes in nuclear stiffness. Treating fibroblasts with farnesyltransferase inhibitors (FTI) restored nuclear stiffness in HGPS cells and accelerated the wound healing response in HGPS and healthy control cells [but] did not improve cellular sensitivity to mechanical strain. These data suggest that increased mechanical sensitivity in HGPS cells is unrelated to changes in nuclear stiffness and that increased biomechanical sensitivity could provide a potential mechanism for the progressive loss of vascular smooth muscle cells under physiological strain in HGPS patients."

Speculating on Oxidative Damage and Diabetes (March 12 2008)
http://ouroboros.wordpress.com/2008/03/12/oxidative-damage-in-the-pancreas/
Thoughs from Ouroboros: "When we think of the ways in which oxidation contributes to age-related decline, it's usually in the context of individual cells: Throughout the body, oxygen radicals accumulate within cells, perhaps as a result of damage to mitochondria, and these reactive oxygen species in turn wreak havoc throughout the cell. This happens, certainly, but the picture is incomplete until we take into account the active cellular response to oxidative damage. ... [researchers] describe how a failure in antioxidant defenses [causes] angiogenesis in the pancreas. The increase in blood flow causes hyperinsulinemia, which causes downregulation of pro-longevity factors throughout the body ... One wonders whether chronic hyperinsulinemia might further stress pancreatic beta cells, as cells throughout the body downregulate the insulin response and become insulin resistant, generating a vicious cycle in which even more insulin resistance is required. Such a mechanism could provide a bridge between oxidation and late-life diabetes, one of the scourges of old age."

More On Grandmothers and Human Longevity (March 11 2008)
http://pmid.us/18322917
Why are humans so very long-lived - albeit nowhere near as long-lived as we'd like - in comparison to other similarly-sized mammals? "The grandmother hypothesis proposes that postreproductive longevity evolved because it is selectively advantageous for females to stop reproducing and to help raise their grandchildren. The mother hypothesis states that postmenopausal longevity evolved because it is advantageous for women to cease reproduction and concentrate their resources and energy in raising the children already produced. ... we test the mother and the grandmother hypotheses with a historical data set from which we bootstrapped random samples of women from different families who lived from the 1500s to the 1900s in the central valley of Costa Rica. ... Here we show that although longevity positively affects a woman's fertility, it negatively affects her daughter's fertility; for this reason, the heritability of longevity is unexpectedly high. Our data provide strong grounds for questioning the universality of the grandmother hypothesis and for supporting the mother hypothesis as a likely explanation for the evolution of human postreproductive longevity."

Rejuvenation Research Presently Free (March 11 2008)
http://www.liebertonline.com/toc/rej/11/1
February's volume 11 number 1 issue of Rejuvenation Research is presently freely available online. These promotions tend not to last forever, so jump on in while the opportunity is there. Of note beyond the science is an interview with David Sinclair of Sirtris Pharmaceuticals: "I see my work as part of an ongoing struggle for improving human life. If I am lucky, I can add one piece to the puzzle, but clearly there will be many more that need to be discovered if we are going to extend lifespan dramatically. I am optimistic that the piece of puzzle we are working on could add a number of healthy years to people’s lives beyond what is currently possible in medicine. And you are correct, that could help people gain access to future technologies. My primary goal, though, is not to extend lifespan so that other technologies will be available, although that may happen as a fortunate consequence. If my work leads to people living an extra five years of healthy life, I would be a very happy person, and perhaps other people can then pick up the baton from that point."

Young Cells Versus Old Microenvironment (March 10 2008)
http://www.eurekalert.org/pub_releases/2008-03/uosf-ioh031008.php
We know that age-related changes in the cellular microenvironment are at least as important as changes within stem cells when it comes to declining regenerative capacity with aging. Can we do anything about that with the biotechnologies of today? Perhaps so: "When human umbilical cord blood cells (UCBC) were injected into aged laboratory animals, researchers [found] improvements in the microenvironment of the hippocampus region of the animals' brains and a subsequent rejuvenation of neural stem/progenitor cells. ... In the brain, there are two stem cell pools, one of which resides in the hippocampus. As in other stem cell pools, the stem cells in the brain lose their capacity to generate new cells. A potent stressor of stem cell proliferation is inflammation ... We think that UCBCs may have a similar potential to reduce inflammation and to restore some of the lost capacity of stem/progenitor cells to proliferate and differentiate into neurons ... Our results raise the possibility that a cell therapy could be an effective approach to improving the microenvironment of the aged brain and restoring some lost capacity."

Arguing the Feasibility of Longevity Medicine (March 10 2008)
http://www.acceleratingfuture.com/people-blog/?p=1870
Another good transcript from Future Current: biomedical gerontologist Aubrey de Grey was asked "to present a case for the feasibility of defeating aging, but of course within the context of the discussion that we are having today overall about the longevity dividend and perhaps more generally about the way we might influence political thinking and public policy in this general area. There is a good deal of dispute among mainstream gerontologists not only as to whether the things that I think are feasible are feasible, but also whether - even if they are - we should really talk about them. I'm going to try and address both of those issues today. ... We all know the study of the biology of aging has consequences for biological disease and suffering. The amount of the bang for the buck, so to speak, that one would get by even very modest interventions to postpone aging is vastly in excess of what is represented by the something in the region of 3% of the public biomedical budget that goes towards the study of aging. If you have a more careful definition as to what is being done to understand aging with a view of doing something about it, then the proportion of public funding that is going toward that is absolutely negligible."

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