Longevity Meme Newsletter, April 21 2008

LONGEVITY MEME NEWSLETTER
April 21 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

- A Doubling of Mouse Lifespan?
- Aubrey de Grey in Orlando, Florida, May 12th
- The Concise Argument For Cryonics
- Discussion
- Latest Healthy Life Extension Headlines

A DOUBLING OF MOUSE LIFESPAN?

You might recall the PEPCK-Cmus mice reported last year: great health and lots of positive improvements in their metabolic biochemistry from a single change in protein expression. They eat hugely, don't put on weight, are very active, and live long:

https://www.fightaging.org/archives/2007/09/another-path-to-mouse-longevity/

I haven't yet had a chance to write a post on the matter, but it begins to look like this genetic manipulation doubles life span in mice. From the latest paper:

http://pmid.us/18394430

"A second surprising result was the apparent extended longevity of the PEPCK-Cmus mice; they lived almost 2 years longer than the controls and had normal litters of pups at 30-35 months of age (most mice stop being reproductively active at 12-18 months). We use the word 'apparent' because we have not as yet carried out a detailed aging study, involving multiple mice, which are followed at regular intervals over their lifetime; this type of study is currently in underway in our laboratory so hopefully we will be able to state unequivocally that the PEPCK-Cmus mice do live longer than controls."

It remains to be seen just how this longevity is achieved - after all, this seems to be a polar opposite to the calorie restriction biochemistry and enhanced longevity associated with lower food intake.

AUBREY DE GREY IN ORLANDO, FLORIDA, MAY 12TH

Longevity science advocate Barbara Logan has organized an evening with biomedical gerontologist Aubrey de Grey at the Orlando Science Center in Florida this May 12th, sponsored by the Millard Foundation:

https://www.fightaging.org/archives/001459.php
http://www.degreyorlando.com/

You'll find fliers and other material at the event website. If you're in Florida this May, it's an excellent chance to hear de Grey speak and ask your questions about longevity science and the repair of aging. Seating is limited, so don't leave it too late to reserve a place.

THE CONCISE ARGUMENT FOR CRYONICS

Working on the development, provision and support of cryopreservation technology is a sensible response to the unfortunate nature of reality:

https://www.fightaging.org/archives/001458.php

"Many people will die before the advent of working rejuvenation medicine, largely from aging, and including many of you reading this now. The only viable option open to these folk is cryopreservation, the low-temperature storage of the brain and body after clinical death. This process can preserve the fine structure of the brain sufficiently well for plausible future technologies to revive a preservee; everything that makes you the person you are is in the structure of your brain. Preserve that, and you can wait as long as needed for the expanding future of medical nanotechnology - and even more advanced science beyond that - to develop the needed tools for revival."

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/

Continuing Discovery of Cancer Stem Cells (April 18 2008)
http://www.eurekalert.org/pub_releases/2008-04/yu-ocs041708.php
Keeping pace with the identification of normal stem cell populations throughout the body, researchers are also isolating the errant stem cells that drive cancer. From EurekAlert!: scientists "have identified, characterized and cloned ovarian cancer stem cells and have shown that these stem cells may be the source of ovarian cancer's recurrence and its resistance to chemotherapy. ... These results bring us closer to more effective and targeted treatment for epithelial ovarian cancer, one of the most lethal forms of cancer ... Present chemotherapy modalities eliminate the bulk of the tumor cells, but cannot eliminate a core of these cancer stem cells that have a high capacity for renewal. Identification of these cells, as we have done here, is the first step in the development of therapeutic modalities." With a clear understanding of the biochemical differences that identify cancer stem cells, researchers can unleash the array of targeted therapies presently performing so well in the laboratory. The elimination of cancer as a threat of old age is very much underway.

An Overview of Cancer Stem Cells (April 18 2008)
http://www.economist.com/science/displaystory.cfm?story_id=11043891
An overview and update on the latest cancer stem cell research, via the Economist: "The cancer-stem-cell theory, though plausible, was based on animal experiments and its relevance to humans was untested. But a series of studies reported this week [has] changed that. They suggest both that cancer stem cells are very relevant indeed to survival, and that going after them is an excellent idea. ... [Researchers] looked at samples from 268 people with pancreatic cancer and found that the pattern of stem cells in their tumours predicted how long they would live. Those whose tumours had stem cells at their edges (the 'invasive margin' in the militaristic jargon of the cancer-warriors) lived on for an average of 14 months. Those who did not lived an average of 18 months. Not a huge difference, but confirmation that cancer stem cells have an impact on the outcome of disease." The path to effective destruction of cancer stem cells - with none of the harm caused by untargeted chemotherapy - is the use of targeted delivery vectors, keyed to the biochemical differences between cancer stem cells and other cells, a technology presently showing great promise in the laboratory.

Doubts on Klotho (April 17 2008)
http://ouroboros.wordpress.com/2008/04/17/time-to-retire-klotho-as-an-anti-aging-factor/
From Ouroboros: "The soluble protein Klotho appears to be an anti-aging factor, since mice deficient in the Klotho gene show signs of premature aging. However, the validity of Klotho-/- mutants as a model of progeria is controversial: many of the pathological features of the mutant phenotype can be attributed to hypervitaminosis D, and can be reversed by eliminating vitamin D from the diet. (Biogerontologists are generally more skeptical of progeria than increased longevity, since there are lots of ways to shorten lifespan that don't involve bona fide accelerating of the aging process, whereas there are far fewer ways to lengthen lifespan without slowing that process down.) Another blow against the idea of Klotho as a regulator of lifespan comes from Brownstein et al. ... from a biogerontological perspective, it's both interesting and sad: Specifically, it’s a strike against the idea that we might be able to supplement aging mammals (like ourselves) with increased levels of Klotho in order to forestall aging."

Another Piece of the Calorie Restriction Puzzle (April 17 2008)
http://www.eurekalert.org/pub_releases/2008-04/uow-rud041708.php
Researchers continue to follow the chained mechanisms by which calorie restriction confers health and longevity benefits. From EurekAlert!: "Previous research has shown that the lifespan-extending properties of dietary restriction are mediated in part by reduced signaling through TOR, an enzyme involved in many vital operations in a cell. When an organism has less TOR signaling in response to dietary restriction, one side effect is that the organism also decreases the rate at which it makes new proteins, a process called translation ... The big question then became what's happening in these translation-deficient cells to slow aging. That's when [we] had the idea to look at Gcn4 ... Gcn4 is a specialized protein called a transcription factor, which helps transfer genetic information during cell growth. The protein is activated when a cell is starving for amino acids. ... To make the link between Gcn4 and longevity, the scientists then asked whether preventing the increase of Gcn4 would block life span extension. In every case, cells lacking Gcn4 did not respond as strongly as Gcn4-positive cells. ... Although scientists don't yet know whether Gcn4 plays a similar role in organisms other than yeast, Kennedy points out that worms, flies, mice and humans all have Gcn4-like proteins that appear to be regulated in a similar way."

Genetic Roots of Parkinson's Disease (April 16 2008)
http://www.mayoclinic.org/news2008-jax/4762.html
Genetic research suggests that Parkinson's disease is not a matter of wear and tear in the brain, but more of an inherited susceptibility to damage: "Inheriting one or both of these mutations doesn't mean that a person will develop Parkinson's disease, but that an individual's risk is increased. The basis of population genetics is that disease is familial; people are so distantly related that they don't know they may have inherited specific genes. While there may be an environmental component to development of the disease, none have been identified that have risks as large as those seen by the LRRK2 gene mutations ... even though there are familial mutations in different locations of the gene, it produces the same effect, the same disease. ... It seems like mutations are occurring in a few founders, and that these founders have a lot of offspring over generations that carry the mutation. Even in sporadic disease, then, familial genes are inherited but symptoms may skip some generations, making the disease appear sporadic." Which suggests that much of Parkinson's could be eliminated via use of a mature gene therapy technology.

Consuming Antioxidants Not So Useful (April 16 2008)
http://www.eurekalert.org/pub_releases/2008-04/w-net041108.php
A metastudy weighs in to demonstrate that antioxidant supplementation has no effect on human life span. Statistics is a dangerous beast, meaning one should never consider this sort of study in isolation, but its far from the only research to show that the standard array of antioxidant supplements don't do much. "The findings of our review show that if anything, people in trial groups given the antioxidants beta-carotene, vitamin A, and vitamin E showed increased rates of mortality. There was no indication that vitamin C and selenium may have positive or negative effects. So regarding these antioxidants we need more data from randomised trials. The bottom line is that current evidence does not support the use of antioxidant supplements in the general healthy population or in patients with certain diseases." If you engineer your antioxidants (or your genes) to target the mitochondria inside your cells on the other hand - the heart and starting point of the mitochondrial free radical theory of aging - then a slowing of aging results. But that doesn't happen when you swallow those supplement pills.

Provoking Stem Cells Into Action (April 15 2008)
http://www.sciencedaily.com/releases/2008/04/080414174848.htm
Given the right cues, our stem cells are capable of far greater feats of healing than take place naturally. Scientists are searching tirelessly for the controlling signals that can put stem cells to work without the risk of cancerous growth. Via ScienceDaily: "researchers screened about 147,000 molecules to find one that could transform human blood stem cells into a form resembling immature heart cells. When they implanted blood stem cells activated by this compound into injured rodent hearts, the human cells took root and improved the animals' heart function. .. Despite medical advances in treating and preventing heart attacks, once the heart is damaged it cannot repair itself ... After a week, the function of the rats' hearts had significantly improved, and after three weeks, the organs contracted as strongly as they did before the damage. Tests showed that the human cells were alive and had incorporated themselves into the heart tissue ... this drug can act on blood stem cells that are already being used in other clinical trials. This may speed its movement into clinical trials for heart repair." Note that screening 147,000 molecules for the one you want is an unremarkable feat these days - biotechnology continues to accelerate, leading to a rate of analysis and progress that would have been impossible 20 years ago.

Calorie Restriction Versus Pancreatic Cancer (April 15 2008)
http://www.eurekalert.org/pub_releases/2008-04/uotm-crd041108.php
EurekAlert! reports that the practice of calorie restriction reduces the risk of pancreatic cancer, in much the same way as it reduces the risk of epithelial cancers: "Prevention of weight gain with a restricted calorie diet sharply reduced the development of pancreatic lesions that lead to cancer [in] a strain of mice that spontaneously develops pancreatic lesions that lead to cancer. ... analysis points to a connection between calorie intake and a protein called Insulin-like Growth Factor (IGF)-1, with obesity increasing and calorie restriction decreasing levels of IGF-1. IGF-1 is an important growth factor known to stimulate the growth of many types of cancer cells. Inflammatory signaling proteins also were found to be reduced in the blood of the calorie-restricted mice. ... The decline in blood levels of inflammatory proteins in the calorie restricted mice makes sense [because] fat tissue is a major source of inflammatory factors such as cytokines."

A View Of Mitochondrial Damage With Age (April 14 2008)
http://pmid.us/18400259
Mitochondrial damage and loss of function with age is an important contribution to many forms of age-related disease, dysfunction and degeneration. Here, an overview of some of the nuts and bolts of that damage: "high-throughput transcription profiles of genes coding for mitochondrial proteins in ventricles from adult (6-months) and aged (24-months) rats were compared using microarrays. Out of 614 genes encoding for mitochondrial proteins, 94 were differentially expressed with 95% downregulated in the aged. The majority of changes affected genes coding for proteins involved in oxidative phosphorylation ... gene expression changes in aged hearts translated into a reduced mitochondrial functional capacity ... aging induces a selective decline in activities of oxidative phosphorylation complexes I and V within a broader transcriptional downregulation of mitochondrial genes." Recall that oxidative phosphorylation is the more efficient mode of operation for mitochondria, and that loss of oxidative phosphorylation is the first step in the mitochondrial free radical theory of aging.

Calorie Restriction and Cancer Risk (April 14 2008)
http://www.eurekalert.org/pub_releases/2008-04/uotm-crl041408.php
Amongst all its other health benefits, calorie restriction appears to also reduce the risk of certain types of cancer: "A restricted-calorie diet inhibited the development of precancerous growths in a two-step model of skin cancer, reducing the activation of two signaling pathways known to contribute to cancer growth and development ... An obesity-inducing diet, by contrast, activated those pathways ... These results, while tested in a mouse model of skin cancer, are broadly applicable to epithelial cancers in other tissues ... Epithelial cancers arise in the epithelium - the tissue that lines the surfaces and cavities of the body's organs. They comprise 80 percent of all cancers. ... Calorie restriction and obesity directly affect activation of the cell surface receptors epidermal growth factor (EGFR) and insulin-like growth factor (IGF-1R). These receptors then affect signaling in downstream molecular pathways such as Akt and mTOR. ... Calorie restriction, which we refer to as negative energy balance, inhibits this signaling, and obesity, or positive energy balance, enhances signaling through these pathways, leading to cell growth, proliferation and survival."

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