Fight Aging!

LONGEVITY MEME NEWSLETTER
October 27 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

- More Thoughts From a Pro-Longevity Bioethicist
- On Recellularization
- Discussion
- Latest Healthy Life Extension Headlines

MORE THOUGHTS FROM A PRO-LONGEVITY BIOETHICIST

It is always interesting to see how the other half of the healthy life extension community presents the ideas and aspirations we hold in common:

https://www.fightaging.org/archives/001595.php

It's a long post and covers a lot of ground, so read the whole thing. The more people to write seriously on these issues, the better - and more so when the community of writers displays a wide range of backgrounds and philosophies, even those you happen to disagree with. Plurality is a sign of progress in support for longevity science, showing that ideas are moving well beyond the original small groups of longevity enthusiasts and researchers.

ON RECELLULARIZATION

Recellularization is a fairly new strategy in tissue engineering, wherein a donor organ is chemically stripped of its cells, leaving only the extracellular matrix structure. This structure is then repopulated with cells from the eventual transplant recipient. Effectively it becomes the recipient's own tissue:

https://www.fightaging.org/archives/001594.php

"A valve from a human or animal donor is removed of all cells using tissue engineering, so that only its outer framework remains. This valve matrix is then colonized with cells that have been obtained from the blood of the recipient and propagated. Within a few weeks, a quasi-natural heart valve then emerges in this bioreactor, that exhibits no rejection response or other faults, but instead grows with the patient after the implantation.

"It's a clever way around our present inability to grow organs from scratch, or generate nanoscale scaffolds as complex as the extracellular matrix. As an added bonus, organs and tissue from animals can be used as the basis for a transplant. ... Recellularization makes xenotransplantation a much more viable technology to fill the tissue engineering gap prior to the ability to grow complex organs from scratch."

Technologies like this will make the replacement of age-damaged organs an important component in biogerontology, at least until more advanced methods of manipulating our cells to regenerate damage arrive.

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/

Another Organ Successfully Grown From Scratch (October 24 2008)
http://www.reuters.com/articlePrint?articleId=USN2237531420081022
From Reuters: "Researchers have discovered stem cells in the prostates of mice and grown complete prostates from them ... human beings have similar stem cells in their prostates, although they have so far not grown human prostate glands from the cells. ... The research team [first] found a marker, a protein, that would differentiate prostate stem cells from other cells in the prostate. This marker, C-117, can also be found in the human prostate ... Other stem cell experts said they doubted Genentech would try to grow human prostates but might use the finding for research into prostate cancer and other prostate conditions. This is a compelling and important study providing strong evidence not only for the presence of stem cells in the adult prostate, but a way to identify them. This extends the number of adult organs in which such tissue-specific stem cells have been found, including skin, brain, mammary glands, and the gut. ... whether you need to regenerate a new prostate is a moot point, since the prostate simply gives the aging male population serious medical problems. However, it is a widely held view that cancers originate from normal stem cells, so this discovery will be a significant boost to prostate cancer research."

On Clearing Amyloid-Beta (October 24 2008)
http://www.eurekalert.org/pub_releases/2008-10/gi-gsf102008.php
At a level somewhere between root cause and symptoms, Alzheimer's is a failure of the mechanisms that clear out amyloid beta (AB) from a healthy brain. Amyloid creation and destruction is a rapid, dynamic process - but if clearance falls just a little behind, then Alzheimer's will develop. So a strategy one step better than patching up symptoms is to somehow improve natural clearance: researchers "discovered that the activity of a potent AB-degrading enzyme can be unleashed in mouse models of the disease by reducing its natural inhibitor cystatin C (CysC). All of us produce AB proteins in the brain. However, in most people, the proteins never build up to dangerous levels because they are cleared away by enzymes that destroy them. Previously Dr. Gan's laboratory had shown that cathepsin B (CatB) is such an AB-degrading enzyme. ... The activity of CatB is regulated by the protease inhibitor CysC. By reducing CysC activity, the scientists were able to unleash the AB-degrading power of CatB, effectively preventing the build-up of AB in [mice]."

Ancient Considerations of Aging and Longevity (October 23 2008)
http://classics.mit.edu/Aristotle/longev_short.html
In 350 BC, Aristotle wrote "The reasons for some animals being long-lived and others short-lived, and, in a word, causes of the length and brevity of life call for investigation. The necessary beginning to our inquiry is a statement of the difficulties about these points. For it is not clear whether in animals and plants universally it is a single or diverse cause that makes some to be long-lived, others short-lived. Plants too have in some cases a long life, while in others it lasts but for a year. Further, in a natural structure are longevity and a sound constitution coincident, or is shortness of life independent of unhealthiness? Perhaps in the case of certain maladies a diseased state of the body and shortness of life are interchangeable, while in the case of others ill-health is perfectly compatible with long life." Slow progress in the investigation of aging and longevity in the centuries since has never been due to a lack of interest, but rather the lack of capable technology. Now that we have the needed biotechnology, isn't it time to move vigorously forward and finish the job?

More On CR Differences Between Species (October 23 2008)
http://ouroboros.wordpress.com/2008/10/22/calorie-restriction-and-igf-1-in-rodents-vs-humans/
As Ouroboros notes, researchers are beginning to uncover differences in the mechanisms of calorie restriction (CR) between species. This lends support to the evolutionary arguments that CR, while demonstrated to be very good for human health, isn't going to extend maximum human life span to the same degree it does in mice. "Decreased IGF-1 levels are associated with increased lifespan. Calorie restriction is also associated with increased lifespan. In rodents, CR is associated with decreased IGF-1 levels, leading to the (still unproven) hypothesis that the effects of CR are mediated by modulation of the IGF-1 axis. In humans, however, the situation is slightly different: As in rodents, the human IGF-1 pathway contains several genes that appear to regulate longevity. The longevity benefits of CR are still under study, but it does appear that certain types of fasting regimens have protective effects against e.g. tumor growth. According to this new study, however, CR has no effect on the levels of functional, circulating IGF-1 [in humans] - so while IGF-1 may regulate longevity and CR may protect against cancer and other age-related maladies, it doesn't appear that CR mediates its effects via IGF-1."

Masters of Our Own Fates (October 22 2008)
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2566596
As this open access paper illustrates, the future of our health is largely in our hands - the vast majority of us are not fated by our genes, but instead by how well we look after our health: "The study sample consisted of 24,043 participants (49.7% women) consisting of 11,186 complete same-sex twin pairs ... Information on retirement [events], including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for [twins] and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement. ... A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age." Largest amongst those "environmental factors" are, I suspect, levels of exercise and calorie intake over the years.

Inflammation, Leucine, and Sarcopenia (October 22 2008)
http://pmid.us/18932012
Researchers who linked an age-related failure in the ability to process the amino acid leucine to progressive muscle loss, or sarcopenia, continue to search for the root cause: "Because aging is associated with changes in oxidative status, we hypothesized that reactive oxygen species-induced oxidative damage may be involved in the impairment of the anabolic effect of leucine with age. The present study assessed the effect of antioxidant supplementation on leucine-regulated protein metabolism in muscles from adult and old rats. ... In old rats, the ability of leucine to stimulate muscle protein synthesis was significantly decreased compared with adults. This defect was reversed when old rats were supplemented with antioxidants [but it] was not related to increased oxidative damage ... These effects could be mediated through a reduction in the inflammatory state, which decreased with antioxidant supplementation. Antioxidant supplementation could benefit muscle protein metabolism during aging, but further studies are needed to determine the mechanism involved and to establish if it could be a useful nutritional tool to slow down sarcopenia with longer supplementation." Given a weight of evidence for the ineffectiveness of ingested antioxidants, a reduction in inflammation and the widespread damage it causes sounds more plausible.

Immune Cells Versus Cancer (October 21 2008)
http://www.eurekalert.org/pub_releases/2008-10/rup-tcr100908.php
The use of immune cells to attack cancer has been going on for many years, but it's only recently that biotechnology has become inexpensive and sophisticated enough to understand why early immunotherapies only sometimes worked. Via EurekAlert!: "One treatment option for patients with late-stage melanoma involves removing natural cancer-fighting T cells from the tumor, expanding their numbers in culture dishes, and then re-infusing them into the patient. This strategy - called adoptive immunotherapy - causes tumor regression in about half the patients treated, some of whom survive for decades without relapse. ... Among the cells taken from a patient who has remained tumor-free for more than a decade, [researchers] found naturally-arising T cells that recognized a new protein, which they dubbed "meloe-1." Meloe-1, the group found, is highly expressed in melanoma cells but not in normal skin cells or in other types of cancer. When they looked at the transferred cells from the other patients, they found meloe-1-specific T cells in 5 of the 9 patients who remained relapse-free, but in none of the 21 patients who relapsed." This sort of knowledge, categorized by cancer type, will lead to highly efficient immunotherapies in the years ahead.

Ouroboros on Aging Research in Yeast (October 21 2008)
http://ouroboros.wordpress.com/2008/10/20/apoptosis-in-yeast/
Yeast has long been important in aging research: "The budding yeast Saccharomyces cerevisiae has been a valuable model system in biogerontology, dating back to the very earliest years of the modern synthesis of molecular genetics with the study of lifespan regulation. From yeast we first learned about the sirtuins, and it continues to teach us much about the mechanisms of lifespan extension by calorie restriction. ... An under-appreciated feature of yeast aging is that [a] yeast cell can die either by necrosis or by programmed cell death - i.e., apoptosis or something very much like it. That comes as a surprise to those of us who grew up thinking of apoptosis as a kind of 'noble sacrifice' made by a damaged cell in the context of a tissue or organ: damage leads to cancer, but not if it leads to cell death first; hence, there's a survival benefit to the organism if individual cells 'voluntarily' die in response to certain types of stress. But with no body to protect, why would a single-celled organism undergo apoptosis?"

Exercise and the Aging Brain (October 20 2008)
http://www.redorbit.com/news/health/1590207/aerobic_exercise_may_slow_reverse_agerelated_brain_decline/
Exercise is much like calorie restriction in that there are few aspects of aging not improved by its practice. From RedOrbit: a review of research "finds that consistent aerobic exercise can prevent age-related decline in brain function, and may even help reverse aging of the brain. ... Moderate physical exercise, at a level that would make a person breathless, has been shown to increase both the speed and sharpness of thought in people with or without signs of Alzheimer's disease or dementia. Furthermore, exercise has also been shown to improve the volume of brain tissue and the way in which the brain functions ... These results suggest that regular aerobic exercise [can] reliably reverse age-related cognitive decline ... many questions remain unanswered [about] the effect of exercise on the brain. However, [we] can safely argue that an active lifestyle with moderate amounts of aerobic activity will likely improve cognitive and brain function, and reverse the neural decay frequently observed in older adults."

Thoughts on Death (October 20 2008)
http://www.depressedmetabolism.com/2008/10/19/death-is-nothing-to-us/
From Depressed Metabolism: "The idea that death gives meaning to life is widespread but does not reflect careful reasoning, and is often a desperate rationalization of human mortality. As a consequence, life extensionists have not been at great pains to defeat 'pro-death' arguments. A (secular) philosophical position that is harder to refute is that we should not fear death because we cannot experience it. This is the classical argument of the ancient Greek philosopher Epicurus ... the position of Epicurus on death is often misunderstood. Epicurus did not argue that we should not fear the process of dying or the prospect of dying. One can prefer life over death without committing to the view that death is bad for a person. Although our survival instinct usually prevents us from looking at it in such a way, in real life we have an ongoing 'choice' between life or death. Although death cannot be experienced as being bad, we generally have good reason to prefer life over death, provided life is experienced as positive or has the potential to become positive. Although life extensionists would prefer to have stronger arguments against the Epicurean view on death, a preference for good experience over no experience can do the work just fine."

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