Fight Aging!

LONGEVITY MEME NEWSLETTER
December 19 2005

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

- 2005: A Great Year For Healthy Life Extension
- Rank 400 For the Longevity Meme Folding Team
- Sirtuins Everywhere
- Discussion
- Latest Healthy Life Extension Headlines

2005: A GREAT YEAR FOR HEALTHY LIFE EXTENSION

2005 was a great year for the Methuselah Foundation and the MPrize for anti-aging research - and thus it was a great year for the future of healthy life extension ... and for the future of your health and longevity. As I've noted many a time, the path towards medical technologies capable of repairing age-related cellular damage is about as clear as scientific research can ever be. The real obstacles - the real uncertainties - lie in attaining the necessary appreciation, support and funding to make it all happen rapidly enough to benefit those of us reading this now.

This past year, the Methuselah Foundation and the MPrize have made a great deal of progress towards these goals - this is the purpose of research prizes and advocacy, to be the stone that triggers the avalanche, the point of view that changes a million minds and sets people to work. Read the following Fight Aging! post for a look back at the highlights, a demonstration of just how far we've come:

https://www.fightaging.org/archives/000700.php

Better still; join the effort to show the world the feasibility of real anti-aging medicine, and the need to commence large-scale research today!

http://www.mprize.org/index.php?pagename=thethreehundred

RANK 400 FOR THE LONGEVITY MEME FOLDING TEAM

The Longevity Meme Folding@Home team has reached rank 400 - congratulations all round and keep up the good work!

https://www.fightaging.org/archives/000695.php

That's a lot of processor time devoted to uncovering the secrets of many age-related conditions related to protein misfolding. You can learn more about the program - and how to join the team - at the Longevity Meme website:

http://www.longevitymeme.org/projects/use_folding_at_home.cfm

SIRTUINS EVERYWHERE

A number of research groups must have been dusting their sirtuin work off for presentation and publicity since the widely reported, and surprising, news of six-fold life extension in yeast resulting from the removal of the sirtuin protein Sir2. You may recall that I mentioned that discovery in a November newsletter:

http://www.longevitymeme.org/newsletter/view_newsletter.cfm?newsletter_id=134

The analogous protein in mammals is called Sirt1, and seems to have much the same relationship to metabolic processes and consequent longevity; this broader investigation into the underlying genes and proteins is an outgrowth of research into calorie restriction and its beneficial effects on life span in almost all species.

https://www.fightaging.org/archives/000671.php

It seems that work was already underway on ways to suppress Sirt1 in adult mammals - sirtuin inhibitors, in other words. Scientists have already investigated genetically engineered mice missing Sirt1, but that modification leads to early developmental abnormalities and few survivors. Suppressing Sirt1 in later life - after any interactions with growth and development have ended - is a whole different experiment, however. We shall have to wait and see how it turns out:

https://www.fightaging.org/archives/000698.php

Given that research into the biochemical intersection between calorie restriction, longevity and metabolism is comparatively well funded at this time, I imagine we'll be hearing something on those mouse experiments by early 2007. Perhaps we'll have a new winner for the MPrize.

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

Founder, Longevity Meme

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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 Potential Arthritis Therapy (December 18 2005)
http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2005/12/18/ncells18.xml
A number of different genetic and gene therapy approaches presently hold out the promise of a cure for arthritis. Here, the Telegraph reports on a different way forward - tissue engineering of replacement cartilage: "Experts from the University of Bristol took just over a month to grow a half-inch piece of cartilage using stem cells, which are self-renewing and have the ability to grow into blood, bones or organs. ... Crucially, the new technique is expected to overcome problems of transplant rejection because the patient's own cells would be used to create the cartilage. ... Tests have shown that the laboratory-grown cartilage is of better quality than any previous attempts at tissue engineering. This means it should be 'springy' enough to work in a knee joint. Transplant trials on NHS osteoarthritis patients are expected within two years."

New Jersey Stem Cell Grants Issued (December 18 2005)
http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20051217-21101800-bc-us-stemcells.xml
Via ScienceDaily: "New Jersey has become the first state to use public money to fund human stem cell research. The state announced $5 million in grants Friday to be split among 17 projects, the New York Times reported. Only three involve human embryonic stem cells, with others studying animals or using adult stem cells." This is small potatoes when compared against the much larger private investment in the field to date. The damage done by anti-research politics - such as attempts to ban vital technologies or whole swathes of medical science - is better measured by the extent to which it scares away risk-averse venture capital than by the posturing of public funding.

On Neurodegeneration (December 17 2005)
http://www.futurepundit.com/archives/003173.html
Randall Parker discusses the future of neurodegeneration and the importance of tackling this range of medical conditions to healthy life extension: "Barring advances in treatment the number of people in the world suffering dementia due to aging will more than triple by the year 2040. ... Obviously, lots of advances in medical treatments will occur in the interim. ... Brain rejuvenation combined with technologies to boost cognitive function will cause an enormous increase in average human productivity. The increases in human productivity will pay back the costs of medical research many times over. We are going to pay for the aging population one way or another. I prefer to pay for it by solving the underlying problem: reverse aging."

Early Nanomedicine (December 17 2005)
http://nanotechwire.com/news.asp?nid=2696
(Via nanotechwire.com). What the mainstream describes as nanomedicine is probably best looked at as the application of nanoscale engineering to existing medical technology. It's a matter infrastructural improvement - smaller, faster, cheaper - and is largely taking place in diagnostics, biotechnology research, and drug delivery. "Nanomedicine is now within the realm of reality starting with nanodiagnostics and drug delivery facilitated by nanobiotechnology. ... There is definite indication of large growth of the market but it will be uneven and cannot be plotted as a steady growth curve. The largest expansion is expected between the years 2010 and 2015." Advanced nanomedicine - such as the use of mass-produced medical nanorobots to replace, enhance, repair or protect existing biological systems in the body - will be built upon a more advanced technology base that is yet to come.

More On Sirtuin Inhibitors (December 16 2005)
http://www.eurekalert.org/pub_releases/2005-12/uoc--fai120805.php
EurekAlert has more on surtuin inhibitors - I imagine that people have been dusting off their research for presentation over the past few weeks now that this area is suddenly hot stuff. "In lab tests, dihydrocoumarin (DHC), a compound found naturally in sweet clover and synthetically manufactured for use in foods and cosmetics, inhibited the activity of Sir2p and SIRT1, forms of sirtuin found in yeast and humans ... It's important to note that the role of sirtuins in aging is conserved in distantly related organisms such as yeast, drosophila and the small roundworm, C. elegans. So, it is not too much of a stretch to expect that sirtuins also control the aging process in mammals, including humans. In addition, sirtuins control many important cellular functions besides aging, and an agent that modulates sirtuins, such as DHC, could not only affect aging but also other critical functions, such as metabolism, neurodegeneration and cancer."

Next Up: Sirtuin Inhibitors (December 16 2005)
http://www.medadnews.com/News/Index.cfm?articleid=299502
Following on the heels of recent surprising insights into the SIR2 protein and longevity in yeast, Elixir Pharmaceuticals is on the way towards developing inhibitors for the human version, SIRT1. "SirT1 represents an important new drug target, given its role in critical cellular processes such as lifespan modulation and the regulation of metabolism. Previously reported SirT1 inhibitors have low potency and low solubility making them poor candidates for drug development. Through Elixir's high-throughput screening campaign, we have discovered several highly selective low molecular weight SirT1 inhibitors that are 500-fold more potent than previously reported SirT1 blockers. These inhibitors are also cell-permeable and orally bioavailable, two characteristics that are invaluable for studying the biology of SirT1 and exploring possible therapeutic uses for SirT1 inhibitors." So it looks like mouse longevity experiments with reduced SIRT1 are in our future.

Stem Cells As Delivery Mechanism (December 15 2005)
http://www.eurekalert.org/pub_releases/2005-12/uow-esc121305.php
Via EurekAlert, an approach to using stem cells to treat neurodegeneration. The cells are engineered "to produce a growth factor known as glial cell line-derived neurotrophic factor (GDNF). In some small but promising clinical trials, GDNF showed a marked ability to provide relief from the debilitating symptoms of Parkinson's. But the drug, which is expensive and hard to obtain, had to be pumped directly into the brains of Parkinson's patients for it to work, as it is unable to cross the blood-brain barrier. ... Svendsen's team implanted the GDNF secreting cells into the brains of rats and elderly primates. The cells migrated within critical areas of the brain and produced the growth factor in quantities sufficient for improving the survival and function of the defective cells at the root of Parkinson's."

Aubrey de Grey Keynote At Health IC (December 15 2005)
http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20051215005827&newsLang=en
Biomedical gerontologist Aubrey de Grey speaks at more conferences in a year than I'll attend in a decade. One of the interesting upcoming events is the Health IC Summit in January: "The Health IC Summit explores disruptive innovations in healthcare, new developments that change the value proposition in the medical field, often quite dramatically. A three-day, four-track conference program of seminars, panels, and roundtables covers new science, technology and business approaches to stem cells and regenerative medicine, innovative patient care, medical informatics and a finance forum. ... Cambridge University's Aubrey de Grey extends the discussion by describing science's eventual cure for aging itself, leading to life spans of a thousand years or longer."

Progeria And Lamin A: Research To Date (December 14 2005)
http://www.medicalnewstoday.com/medicalnews.php?newsid=34919
From Medical News Today, a look back at two years of amazing progress in Progeria research: "researchers made a breakthrough in 2003, tracing [Progeria] to a spontaneous mutation in a gene encoding an important structural component of the cell nucleus, the organelle in which our DNA is stored, read out, and copied. ... The second set of results reveals mutant [lamin A] proteins turning up in the wrong place - too tightly linked to the membranes of the nuclear envelope - to be of much help during key stages of the cell cycle. The researchers believe that this localization failure of mutated [lamin A] proteins would severely compromise the ability of [Progeria] cells to engage in normal DNA replication, a probable factor in their rapid march to premature senescence. Whether similar missteps and miscues by nuclear lamins are part of 'normal' human aging is the question that draws researchers onward."

Control Is The Key To Cell Therapies (December 14 2005)
http://www.eurekalert.org/pub_releases/2005-12/ohs-ods121405.php
From EurekAlert, a good demonstration of the sort of control over cellular processes that is at the heart of progress in cell therapies: "The key gene that the scientists studied is called brahma-related gene-1 (Brg-1) that is found in both mice and humans. ... This research shows us that in mice, Brg-1 is a critical signal that prevents stem cells from turning into neurons at the wrong time. However, since we can manipulate Brg1 expression in stem cells in culture, we now have a powerful way to generate neurons that could be used to replace cells lost in a variety of diseases and conditions that affect the brain and spinal cord. That is our next step. Since the process only involves a single gene, it is highly amenable for the development of drugs targeted at promoting stem cell differentiation in the adult nervous system."

The Ongoing Search For Longevity Genes (December 13 2005)
http://www.betterhumans.com/News/5023/Default.aspx
Betterhumans notes another modest step forward in attempts to match genes with longevity or resistance to age-related disease (although I would object to any use of the term "successful aging" - no such thing! Yet). "While previous research found that genes make important contributions to exceptional longevity, the goal of this study was to identify regions of the human genome that contributed, along with lifestyle factors, to reaching age 90 with preserved cognition. ... Specifically, Dr. Zubenko and his research team attempted to identify specific genetic sequences present in older individuals that may be linked to reaching older ages with preserved cognitive abilities, or conversely, specific genetic sequences present in younger individuals (and not present in those over age 90) that may impede successful aging."

Insight Into Werner Syndrome (December 13 2005)
http://www.newswise.com/articles/view/516789/
Investigations into accelerated aging conditions have helped to shed light on the biochemistry of "normal" aging. Via Newswise: "A University of Maryland researcher and his team have discovered a key to the cause of the accelerated aging disease Werner syndrome ... caused by a genetic mutation of a specific gene - the WRN gene, which some scientists think hold the key to understanding something about the aging process. Scientists also know that humans have five types of RecQ helicase proteins, including the WRN protein, which is expressed by the WRN gene. These proteins function as safeguards to maintain genome integrity. Mutations in three RecQ helicase proteins have been linked to genetic diseases. But they don't know what goes wrong in this group of proteins that causes the aging process to go haywire. Hu and his team singled out the WRN protein, or enzyme, to look for some answers."

Overhyped, But Interesting (December 12 2005)
http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20051212-16032200-bc-us-stemcells.xml
(Via the Muskogee Phoenix). A research team are claiming their discovery of pluripotent stem cells in bone marrow to be an important discovery: "University of Louisville researchers have coaxed stem cells from adult mice to change into brain, nerve, heart muscle and pancreatic cells." I think this is greatly overhyped; small pluripotent - or even pseudo-embryonic - cell populations have been discovered elsewhere in the body over the last year or two. This is not to demean the promise offered by a local source of suitable adult stem cells for tissue engineering and regenerative medicine - it's a big deal. But that isn't cause to issue calls to halt the vital work of embryonic stem cell research.

Regrowing Pancreatic Islets (December 12 2005)
http://www.sciam.com/article.cfm?chanID=sa004&articleID=00065EBC-A93F-137B-A7A583414B7F0000
From Scientific American, a look at progress towards diabetes therapies in the form of regenerative medicine for the pancreas: "In newly diabetic mice, the results were spectacular. After two weeks of treatment, the beta-cell mass had tripled, the insulin content had increased eightfold, and the blood glucose concentration had fallen to normal levels. It did not go so well in mice with long-standing diabetes: their glucose levels fell substantially, yet they needed some immunosuppressive medication. ... Even a partial regeneration in patients would at least get around the shortage of donor tissue and would probably require less immunotherapy; native cells would need defense from autoimmunity alone, not from that and organ rejection combined."

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