Longevity Meme Newsletter, December 01 2008

LONGEVITY MEME NEWSLETTER
December 01 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

- The Millard Foundation and Longevity Science Funding
- Deuterium and Oxidative Damage
- That Time Again: Year End Donations
- Discussion
- Latest Healthy Life Extension Headlines

THE MILLARD FOUNDATION AND LONGEVITY SCIENCE FUNDING

Interesting news from the Methuselah Foundation prompts a look at some of the funding sources for modern longevity science:

https://www.fightaging.org/archives/001621.php
http://blog.methuselahfoundation.org/2008/11/onward_and_upward_for_a_methus_1.html

"The Millard Foundation has been moving towards earnest funding of longevity science over the past few years: there have been initial donations, conference attendances, meetings with movers and shakers. All the normal activities and preparation by people who take investing very seriously. Much like the Glenn Foundation, which I would consider an analogous force in the philanthropic funding space, the Millard family have donated generously to the Methuselah Foundation. But where Paul Glenn opted to place his first major funding initiatives firmly in the present mainstream - calorie restriction research, understanding metabolism, and attempts to slow aging through metabolic and genetic manipulation - the Millard family is more inclined towards the Strategies for Engineered Negligible Senescence (SENS) viewpoint."

Judging by the sounds coming from behind the scenes at present, an important new initiative is getting underway. Details will no doubt emerge when the Millard Foundation is ready to announce them.

DEUTERIUM AND OXIDATIVE DAMAGE

A great deal of longevity science falls into the "interesting, but impractical" camp. I think that recent work on the effects of deuterium on longevity in lesser animals is a good example of the type:

https://www.fightaging.org/archives/001620.php

"Dr Shchepinov's theory is based on deuterium, a naturally-occurring isotope, or form of hydrogen, that strengthens the bonds in between and around the body's cells, making them less vulnerable to attack. He found that water enriched with deuterium, which is twice as heavy as normal hydrogen, extends the lifespan of worms by 10 per cent. And fruitflies fed the 'water of life' lived up to 30 per cent longer.

"As for the other folk quoted in [a science press article at the time], I'm dubious - it seems to me that the level of technology required to target the isotopes reliably (and keep them targeted) would enable far more effective methodologies of repairing rather than preventing oxidative damage."

The theory is sound - changes in atomic properties leading to resistance to oxidative damage - but implementation in humans seems very impractical in comparison to other avenues of longevity science you could pursue with the same amount of time, expertise, and money. Not that any of you will be running out to pick up vats of deuterium-enriched heavy water, but I suppose that I should note it is toxic to mammals at high concentrations.

THAT TIME AGAIN: YEAR END DONATIONS

As I noted this past week, I'm switching my yearly donation to the Methuselah Foundation from the Mprize fund to SENS research:

https://www.fightaging.org/archives/001622.php

"This year's donation will go towards SENS research - but not because I think the Mprize is any less worthy. At this point, it looks like the best plausible growth path for the Methuselah Foundation over the next few years is based on following through with present initiatives to establish and publicize a steady stream of modest SENS research achievements. I've long said that advocacy and tangible results have to go hand in hand for optimal progress; when one gets too far ahead of the other, it tends to slow down.

"You get what you pay for in this life - so if we want to see that steady stream of research achievements, we have to fund the research. Other people hang around in the wings waiting for more confirmation and mass of support for these projects, but those of us who better understand the science and potential of SENS are the ones who must pay to start the ball rolling. My contributions aren't large, but then no one person can form a crowd. I would hope that discussing this topic moves those of you yet to donate to make that small effort to help progress towards engineered longevity."

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/

Glancing at Autologous Stem Cell Therapies (November 28 2008)
http://www.marketwatch.com/news/story/story.aspx?guid=%7B1B211376-C24C-4B2C-B881-7FF71EB82AAB%7D
The provision of autologous stem cell therapies in the for-profit world continues onwards, as this press release indicates: researchers "announced nine month follow up results for the first patient treated with engineered stem cells in a clinical study of primary pulmonary hypertension. The stem cells are extracted from patients' own blood and trained to become new blood vessels. ... It goes against traditional theory that we should try to fix the existing pulmonary vasculature, but we are generating new blood vessels with impressive results. ... the clinical study is a collaborative effort amongst physicians at Regenocyte Therapeutic, a Florida-based stem cell clinic; researchers from TheraVitae, a biotechnology company in Tel Aviv, Israel; and physicians from Regenocyte's Dominican Republic division. ... This is the first time medical science has successfully reversed the disease process in pulmonary hypertension, a previously untreatable condition with a very grim prognosis. Using advanced engineered stem cell technology and innovative delivery methods. We've been able to harness the regenerative power of stem cells and literally replace the damaged blood vessels in the lungs of the pulmonary hypertension patients."

Uncovering Plasticity in the Adult Brain (November 28 2008)
http://www.sciencedaily.com/releases/2008/11/081124174909.htm
From ScienceDaily: "Overturning a century of prevailing thought, scientists are finding that neurons in the adult brain can remodel their connections. ... [researchers] saw relatively large-scale changes in the length of dendrites - branched projections of nerve cells that conduct electrical stimulation to the cell body. Even more surprising was their finding that this growth was limited to specific type of cell. The majority of cortical neurons were stable, while the small fraction of locally connecting cells called interneurons underwent dynamic rearrangement. ... the capacity of interneurons to remodel is not predetermined by genetic lineage, but imposed by the circuitry within the layers of the cortex itself. ... Our findings suggest that the location of cells within the circuit and not pre-programming by genes determines their ability to remodel in the adult brain. If we can identify what aspect of this location allows growth in an otherwise stable brain, we can perhaps use it to coax growth in cells and regions that are normally unable to repair or adjust to a changing environment."

The Optimal Calorie Restriction Window (November 27 2008)
http://pmid.us/19032694
Previous studies suggest that it's never too late to gain significant health benefits by adopting a calorie restriction diet. Here is an intriguing paper that suggests there is a cut-off if you want those benefits to include an improved immune system: "We have recently shown in non-human primates that caloric restriction (CR) initiated during adulthood can delay T-cell aging and preserve naive CD8 and CD4 T cells into advanced age. An important question is whether CR can be initiated at any time in life, and whether age at the time of onset would modulate the beneficial effects of CR. In the current study, we evaluated the impact of CR started before puberty or during advanced age on T-cell senescence and compared it to the effects of CR started in early adulthood. Our data demonstrate that the beneficial effects of adult-onset CR on T-cell aging were lost by both early and late CR onset. In fact, some of our results suggest that inappropriate initiation of CR may be harmful to the maintenance of T-cell function. This suggests that there may be an optimal window during adulthood where CR can delay immune senescence and improve correlates of immunity in primates."

Another Way to Look at DNA Damage and Aging (November 27 2008)
http://pmid.us/19029623
It is a widely held view that accumulating stochastic nuclear DNA damage is one contributer to aging. This is debated for degenerations other than cancer, however. Here is a different way of looking at DNA damage in stem cells, connected to the immortal DNA strand (IDS) hypothesis: "Cairns noted a mathematical discrepancy between predicted human tissue cell mutation rates and human cancer incidence [and predicted] the existence of IDSs as the essential elements of a mutation-defense mechanism in [stem cells]. ... several laboratories have identified IDSs in diverse mammalian [stem cells]. Past studies focused on the potential roles of IDSs as originally envisioned in [stem cell] genetic fidelity or in the maintenance of the [stem cell] phenotype. Another possible consequence of IDSs, aging, has received little attention. Herein, the potential for cumulative chemical modifications and decompositions (i.e., 'age spots') of IDSs in [stem cells] to act as a major determinant of human aging is considered. If accrued chemical alterations of IDSs prove to be essential determinants of aging, then a means to restore IDSs may yield new strategies for tissue rejuvenation."

The Metabolic Stability Theory of Aging (November 26 2008)
http://pmid.us/19031007
There are a lot of theories of aging, some very useful, many of which overlap, and many of which are overly narrow, overly general, or otherwise unhelpful. Here's one that appears to be another way of looking at damage accumulation, or perhaps reliability theory: "Individual differences in the rate of aging are determined by the efficiency with which an organism transforms resources into metabolic energy thus maintaining the homeostatic condition of its cells and tissues. This observation has been integrated with analytical studies of the metabolic process to derive the following principle: The metabolic stability of regulatory networks, that is the ability of cells to maintain stable concentrations of reactive oxygen species (ROS) and other critical metabolites is the prime determinant of life span. ... Our studies delineate age and tissue specific patterns of transcriptional changes which are consistent with the metabolic stability-longevity principle. This study, in addition, rejects the free radical hypothesis which postulates that the production rate of ROS, and not its stability, determines life span."

New Scientist on Sirtuins (November 26 2008)
http://www.newscientist.com/article/dn16143-has-universal-ageing-mechanism-been-found.html
The New Scientist (and some of the interviewed researchers) overhype an interesting discovery: "An overworked protein that causes yeast to age when it neglects one of its functions may trigger ageing in mice too. ... As we get older, genes can start to be expressed in the wrong body tissues - a process that is thought to contribute to diseases like diabetes and Alzheimer's. ... yeast cells [produce] a dual-function protein called Sir2 that, while being involved in DNA repair, also helps keep certain genes switched off. As yeast cells age, the protein can't do both jobs and neglects its role as a gene suppressor. Now Sinclair's team has shown that SIRT1, the mammalian version of Sir2, also begins to neglect its gene-suppressor role in mice whose DNA is damaged, and that this may contribute to ageing. ... The most exciting thing is that this work may unify in a single molecular pathway what we know about ageing in different organisms such as yeast and mammals ... It opens up the possibility of restoring youth in the elderly by re-establishing a useful pattern of gene expression." I think it will take more than restoring gene expression: there's also the matter - more important to my mind - of repairing the damage that caused those changes in gene expression.

Bone Made To Order (November 25 2008)
http://www.telegraph.co.uk/health/3519161/Custom-made-bones-to-be-grown-within-hours.html
From the Telegraph: "The world's first custom-made bones that can be 'grown' in a matter of hours and fit precisely into a break could be available within three years. The new bones will replace damaged or ceramic versions that are currently used in reconstructive surgery. They are made of one of the key materials in human bone, calcium phosphate, which means they will not be rejected by the body and will be completely absorbed into the skeleton within a couple of years. ... We have just completed the investigative study and clinical trials are under way on patients. Some people have congenital defects, others have lost bone after undergoing surgery for cancer, while others have been in traffic accidents. The reactions we have had so far have been very favourable." Early days yet, along with flaws and limitations to the process, but this sort of medical engineering will improve just as rapidly as other biotechnology.

Steady Progress in Regenerative Medicine (November 25 2008)
http://www.eurekalert.org/pub_releases/2008-11/chop-chs112508.php
Advances of the sort noted here at EurekAlert! are becoming commonplace: researchers "have been able to effectively repair damaged heart muscle in an animal model using a novel population of stem cells they discovered that is derived from human skeletal muscle tissue. ... These transplanted [cells] repaired the injured muscle, stimulated the growth of new blood vessels in the heart and reduced scar tissue from the injury, thereby dramatically improving the function of the injured left ventricle ... This study confirms our belief that this novel population of stem cells discovered in our laboratory holds tremendous promise for the future of regenerative medicine. Specifically, myoendothelial cells show potential as a therapy for people who have suffered a myocardial infarction. The important benefit of our approach is that as a therapy, it would be an autologous transplant. This means that for a patient who suffers a heart attack, we would take a muscle biopsy from his or her muscle, isolate and purify the myoendothelial cells, and re-inject them into the injured heart muscle, thereby avoiding any risk of rejection by introducing foreign cells."

A View of Veterinary Regenerative Medicine (November 24 2008)
http://www.thehorse.com/ViewArticle.aspx?ID=13147
Regenerative medicine for animals is more advanced than that available for humans, as regulation is less oppressive. Here, a view of regenerative medicine for horses: "Tendon and ligament injuries in performance horses are the most common disorders currently being treated with stem cells in clinical trials ... One researcher has shown a lower recurrence rate of bowed tendons in racehorses treated with stem cells ... Clinical trials with local stem cell injection are also being performed for treatment of suspensory ligament injuries of the fore and hind limbs. ... Degenerative joint disease is a problem in performance horses and has great economic impact on the equine industry. Although there are many therapies to support joint health, the majority of these treatments are to relieve the symptoms at best. Stem cell therapy for joint disease is supported by original research performed in goats. It was shown [that] joints treated with stem cells had less arthritic changes compared with nontreated joints in the same animal. Several horses have been experimentally treated for joint injuries [using] stem cell therapy and the initial results have been positive."

Wired on Longevity Drugs (November 24 2008)
http://blog.wired.com/wiredscience/2008/11/two-mice-on-tre.html
From Wired: "Resveratrol has proven safe in animals and early clinical trials, but much more testing is required. As a cautionary, Longo offered the example of his own research on caloric restriction and genetic manipulation of IGF-1, a cell-growth-regulating gene. In simple organisms, it's produced the most-dramatic life extension ever seen - yeast lived 10 times its normal lifespan - but a group of Ecuadorians who naturally have that mutation have severe growth deficits and other health problems. Even Longo, however, thinks resveratrol will enjoy some success in the near future, and mitochondrial approaches are being steadily embraced within the medical research community, which has been largely frustrated in its disease-by-disease, gene-centered approach. ... The approach we've taken is to go one disease at a time. We've created national institutes to go after all these major diseases, and every time we identify a new gene, or do something that lets us attack disease a little more efficiently than before, everyone jumps up and says we've succeeded and that's wonderful. Such research is important, said Olshansky, but not as promising as hitting diseases at a common root. And though he won't yet commit to resveratrol as a wonder drug, he suspects that mitochondria-targeting drugs will provide a breakthrough."

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