Fight Aging!

LONGEVITY MEME NEWSLETTER
November 21 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

- Problems With Delivery to Yahoo! Mail Addresses
- Sixfold Life Extension Demonstrated In Yeast
- Discussion
- Latest Healthy Life Extension Headlines

PROBLEMS WITH DELIVERY TO YAHOO! MAIL ADDRESSES

Newsletters for the past few weeks have been swallowed or otherwise misdirected by the receiving Yahoo! Mail systems. Hopefully these problems have been resolved. If you have a Yahoo! Mail address and feel you've missed any of the newsletters for recent weeks, you can find them archived in the "Past Newsletters" section of the following page:

http://www.longevitymeme.org/newsletter/

SIXFOLD LIFE EXTENSION DEMONSTRATED IN YEAST

The big story of this past week is an abrupt and unexpected twist in attempts to understand how calorie restriction extends healthy life span, and how metabolism and longevity are regulated. You'll find a summary and discussion in the following Fight Aging! posts:

https://www.fightaging.org/archives/000669.php

"Scientists have known for several years that an extra copy of the SIR2 gene can promote longevity in yeast, worms and fruit flies. That finding was covered widely and incorporated into anti-aging drug development programs at several biotechnology companies. Rather than adding copies of SIR2 to yeast, Longo's research group deleted the gene altogether. The result was a dramatically extended life span -- up to six times longer than normal -- when the SIR2 deletion was combined with caloric restriction and/or a mutation in one or two genes, RAS2 and SCH9, that control the storage of nutrients and resistance to cell damage."

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

A study on mice lacking the mammalian equivalent of SIR2, the Sirt1 gene, appears to have been carried out back in 2003: "What they found in the mice that were able to survive that despite growth defects and sterility that they shared some of the effects associated with long lived IGF1-deficient mice. It appears that Sirt1 has a developmental function and should not be altered during embryonic development. So the interesting question is why would Sir2 overexpression confer a modest lifespan increase but Sir2 deletion confer substantial lifespan extension?"

Research into the biochemical and genetic roots of longevity, metabolic regulation and calorie restriction has been ongoing in earnest for only a handful of years, and this is just the latest plot twist of many. I have not been optimistic that any form of radical life extension will fall out of metabolic and genetic tinkering. Other methodologies based on repair or prevention - such as those of the Strategies for Engineered Negligible Senescence - seem to be a better approach to the problem of age-related cellular damage. But who knows? Given just the size and life span of whales, to pick one example, it would appear that there is room for sizeable improvement to human biochemistry in terms of resisting age-related decline.

https://www.fightaging.org/archives/000384.php

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/

Watching VesCell, TheraVitae (November 20 2005)
http://www.genengnews.com/news/bnitem.aspx?name=1108101XSL_NEWSML_TO_NEWSML_WEB.xml
As you may recall if you read Fight Aging!, TheraVitae is attempting to commercialize offshore stem cell treatments for US residents; the degree to which they succeed will certainly be widely noted in the venture investment community. This release at Genetic Engineering News gives some indications as to how the effort is going: TheraVitae has "presented interim clinical data showing significant improvement in patients suffering from severe angina pectoris six months after they received the company's autologous adult stem cell therapy. ... The benefit to patients' quality of life is a particularly positive aspect of the results we have seen and has convinced us to start treating patients with no other therapeutic options outside of the clinical trial. Thus, several dozen patients with severe angina and/or heart failure have already been treated off trial in Thailand."

Alzheimer's And The Urge To Progress (November 20 2005)
http://news.enquirer.com/apps/pbcs.dll/article?AID=/20051120/EDIT02/511200360/1021/EDIT
Modern Alzheimer's research is an example of the sort of success story that starts with determined patient advocacy and a few scientists, leading to a huge and well-funded research community, now close to cracking the problem. From the Enquirer: "much has changed over the past two decades. Today, there are four FDA-approved drugs available to temporarily relieve some symptoms of the disease. Even more encouraging are the advances being made in our understanding of Alzheimer's. Researchers are getting closer to conquering Alzheimer's, with breakthrough studies published almost weekly." Healthy life extension activists could do worse than to repeat the successes of Alzheimer's, AIDS and cancer advocacy in helping to create dedicated, well-funded research communities.

Stem Cells, Statins (November 19 2005)
http://www.medicalnewstoday.com/medicalnews.php?newsid=33769
It seems that at least some of the high-level benefits of statin drugs for heart disease patients may come from their effects on stem cells: "pravastatin, the generic name of one of the statins currently prescribed to lower cholesterol, increased the concentration of endogenous stem cells that may participate in cardiac repair independent of any cholesterol-lowering action. ... In addition, many newly formed myocytes -- heart muscle cells that aid in repair of damaged tissue -- were detected. While increased stem cells were seen after pravastatin in normal hearts as well, they only resulted in myocyte growth and development in diseased hearts." This is interesting; how many other treatments might have accidental stem cell contributions?

More On Recent Longevity Research (November 18 2005)
http://www.guardian.co.uk/science/story/0,3605,1645418,00.html?gusrc=rss
A post at Fight Aging! will give you the background on new and interesting research into longevity, metabolism and the Sir2 gene in yeast, but you'll find more at the Guardian: "When you do this genetic manipulation, you can get some of the longest lifespans [in yeast] ever described. We have good reason to believe this genetic effect is conserved in other organisms. We're working with mice and human cells now and are already starting to see the same response. ... When you start increasing lifespan by five or six times, it means you're really playing with the life and death programmes of organisms. We're telling the organisms to go into a completely different mode of slow ageing. What they're doing is saying 'I cannot afford to age. I still have to generate offspring, but I don't have enough food to do it now.'"

Immune System Versus Cancer (November 18 2005)
http://www.medicalnewstoday.com/medicalnews.php?newsid=33688
A rather clever approach to cancer immunotherapy is detailed at Medical News Today: "The vaccine, originally developed at Johns Hopkins, uses irradiated pancreatic cancer cells incapable of growing, but genetically altered to secrete a molecule called GM-CSF. The molecule acts as a lure to attract immune system cells to the site of the tumor vaccine where they encounter antigens on the surface of the irradiated cells. Then, these newly armed immune cells patrol the rest of the patient's body to destroy remaining circulating pancreatic cancer cells with the same antigen profile. ... Even though our results are preliminary, the survival rates are an improvement over most published results of pancreatic cancer treatment studies." It remains to be seen how effective this methodology can become - reliable treatments or preventions for cancer are an essential part of extending the healthy human life span.

Longevity Genes In Yeast (November 17 2005)
http://www.eurekalert.org/pub_releases/2005-11/hhmi-run111605.php
Yeast and roundworms are where the search for longevity-determining genes often begins, as demonstrated in this EurekAlert piece: "Howard Hughes Medical Institute researchers and their colleagues have now uncovered 10 new genes that regulate longevity in yeast. The studies also suggest a new model for how aging is slowed when caloric intake is restricted. ... We'd like to understand how aging occurs in yeast. Even though yeast is a simple, single-cell organism, it's still capable of revealing mechanisms in the aging process. Similar genes may control aging in higher organisms, too. ... The two years of laboratory work, much of it done by Kaeberlein and Kennedy, were extraordinarily tedious, involving complex genetic and biochemical tests on a special collection of 4,800 strains of yeast cells developed by other scientists."

Towards Biopacemakers (November 17 2005)
http://www.eurekalert.org/pub_releases/2005-11/jhmi-ctc111105.php
EurekAlert reports further steps towards the creation of biological alternatives for artificial pacemakers: "In guinea pig experiments, Johns Hopkins scientists fused common connective tissue cells taken from lungs with heart muscle cells to create a safe and effective biological pacemaker whose cells can fire on their own and naturally regulate the muscle's rhythmic beat. ... Other biopacemaker technologies, Cho notes, use adenoviruses as part of gene therapy to carry pacing genes into the heart, or use combinations of gene- and stem-cell therapies that may cause cardiac inflammation or uncontrolled cell growth that cause arrhythmias instead of stopping them. ... It is very difficult to guide stem cells into forming exactly the kind of cell needed, but not so with fibroblasts."

More Cartilage From Stem Cells (November 16 2005)
http://www.imperial.ac.uk/P7061.htm
Scientists have succeeded in producing cartilage from human embryonic stem cells. Regenerative medicine for cartilage is important, as this tissue is particularly difficult to heal or replace: "The research involved growing human embryonic stem cells with chondrocytes or cartilage cells, in Petri dishes in the laboratory in a specialised system that encouraged them to change into cartilage cells. When this was compared with just growing the human embryonic stem cells alone, the mixed stem cells and cartilage were found to have higher levels of collagen, the protein constituent of cartilage." Other groups have already succeeded in tissue engineering cartilage, but this new work would appear to be a helpful addition to our understanding of embryonic stem cells and ability to control their differentiation.

Missing The Point, Part II (November 16 2005)
http://news.bbc.co.uk/2/hi/uk_news/magazine/4442020.stm
An article from the BBC on radical life extension manages to avoid the Tithonus error - "It is argued that scientific advances in anti-ageing treatments means living longer will not place a burden on health care, because it will increase people's health span and not just add some extra years in a care home with little quality of life" - but falls right into the trap of assuming that retirement behavior will remain unchanged: "With retired people struggling by on an average income of about £11,000, more and more are going to live with their children because rising health, heating and council tax costs make it harder for them to keep their home." This is simply ridiculous - if you are an experienced, skilled 120-year-old and as fit, healthy and active as today's 50-year-olds, are you going to live in penury or go out and get a job?

Engineered Blood Vessels In Trials (November 15 2005)
http://www.webmd.com/content/Article/115/111636.htm?printing=true
WebMD reports on human trials of tissue engineered blood vessels: "This is the world's first implantation of a tissue-engineered blood vessel produced in the laboratory. ... The vessels are built with the patient's own cells ... blood vessels have either been grown or are in the process of being grown for six patients. Two have been implanted in kidney dialysis patients to offset damage in shunts placed in blood vessels of their arms used for dialysis. A third patient is expected to have the implant early next year. The team is able to take two cell types - skin and the inner lining of vessels - from the patient's own body. The skin is grown into sheets, wrapped around a medical tube, and fused together, forming a vessel. Just before implantation into the patient, cells grown from the inner lining of the patient's own veins are cultured and grown within the engineered vessel."

AGE-Breakers In The News Again (November 15 2005)
http://www.newswise.com/articles/view/516084/
Progress on developing useful AGE-breakers - drugs capable of breaking down damaging chemical crosslinks and advanced glycation endproducts (AGEs) that accumulate with age - never seems to be as fast as advocates would like. Via Newswise, however, we have some signs of movement: "This is the first demonstration that this class of drugs, known as collagen-crosslink breakers, can turn back the clock and make old arteries behave like young ones ... These results confirm that this drug does have important effects on the aging process in the arteries, but we still have to prove that there's some benefit to patients in terms of reducing cardiovascular disease. Our next step will be a study, expected to begin in late 2006, of the drug's potential benefit at preventing or reversing heart failure in the elderly."

Better, Faster Dopamine Cells (November 14 2005)
http://www.scienceblog.com/cms/biologist_coaxing_stem_cells_to_make_dopamine_in_simpler_faster_method_9290
Sometimes the difference between promising lab work and viable basis for commercial therapy is a simple doubling of efficiency - infrastructure is at the heart of progress. Here, ScienceBlog reports on improvements in the production of stem cells to treat Parkinson's disease or similar age-related conditions: "For all of the promise embryonic stem cells hold for therapies for neurodegenerative diseases such as Parkinson's disease, they are notoriously difficult to use. One problem is in coaxing them into becoming brain cells that make dopamine, which is in short supply in the brains of individuals with Parkinson's. ... We have been able to show we could generate a process in the tissue culture dish that is simple, rapid, and uses defined reagents, most of which are human products. We can make them into dopamine neurons in a dish, and they are mature."

Stem Cell Plasticity, Brain Repair (November 14 2005)
http://www.the-scientist.com/2005/11/7/20/1
The Scientist looks at what can and can't be done with adult stem cells: "the scientific debate persists as to whether adult stem cells are multipotent, or if they even need to be in order to be therapeutically relevant. ... both authors came to similar conclusions about the implications of their findings. 'We both speculated that it may be serving a positive function in neurodegenerative disease, repairing tissues that are damaged,' says Blau, who notes that earlier studies in animals showed that tissue damage enhances bone marrow cell contribution. ... Wagers contends that even if bone marrow cells do in fact contribute to brain, the contribution is too low to be therapeutically beneficial. "But if you wanted to take an approach of trying to enhance that contribution, then it would be important to know the mechanism by which it was occurring.'"

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