Longevity Meme Newsletter, November 06 2006
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LONGEVITY MEME NEWSLETTER
November 06 2006

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

- Resveratrol Everywhere
- The Cost of Progress
- Discussion
- Latest Healthy Life Extension Headlines

RESVERATROL EVERYWHERE

One of the perks of having accepted significant venture funding for your biotech startup company is the ability to coordinate an avalanche of press with progress towards your goals. This was very much in evidence in the past week as Sirtris Pharmaceuticals moves towards larger trials of a form of resveratrol, a calorie restriction mimetic. A modest selection of links to video and recent press can be found here:

https://www.fightaging.org/archives/001023.php

As many of you know by now, I'm not a big enthusiast of the pill, drug discovery and metabolic manipulation school ("old school") of healthy life extension. A fairly representative sample of my views on that score can be found in the following recent post:

https://www.fightaging.org/archives/001020.php

"Metabolic manipulation is hard to perform safely; it's an enormously complex system, and dire consequences can be waiting to leap out decades down the line. Researchers are spending hundreds of millions of dollars on the problem, with the goal of perhaps a decade or two of healthy life extension as the end result, a decade or two from now. Not to be sniffed at - but you will still age, suffer and die."

THE COST OF PROGRESS

As the comments on that last post demonstrate, I'm probably not doing a good enough job of communicating the basis for my point of view. After all, I'm a supporter of calorie restriction, so why am I not an enthusiastic supporter of aggressive research into calorie restriction mimetic drugs like resveratrol? It runs something like this:

1) The vast majority of the comparatively small amount of resources and infrastructural development dedicated to the fight against aging is directed towards metabolic manipulation. This means attempts to engineer a slowing of aging via tuning the body's metabolic processes to generate damage at a slower rate. Much of the work springs from investigations of the biochemistry of calorie restriction and its health and longevity benefits.

http://www.longevitymeme.org/topics/calorie_restriction.cfm

2) If the results of this work came free of cost, I'd be happy to accept them as a stepping-stone to more effective science in the decades ahead. If an extra decade is dropped in your lap, there's a lot you can do with that.

3) Practicing calorie restriction is free, but research is not. The present purposing of the aging research community to metabolic manipulation is expensive, but money isn't the real concern. An opportunity is being lost: the real cost is the slowdown in developing a research infrastructure that is instead purposed towards identification and repair of aging damage, a more efficient way forward to extended healthy lives. This is the difference between tuning your engine and taking it to a mechanic: tuning gets you so far and so far only; at some point, you're going to have to repair the components.

http://www.longevitymeme.org/topics/strategies_for_engineered_negligible_senescence.cfm

4) It does you no good in the long term to buy an extra decade of healthy life if that's all you get; it was only useful if researchers spent that decade working hard on repairing aging, rather than further metabolic science. There's only so much you can do with slowing aging through metabolic manipulation - the elderly wouldn't benefit, for example - but a working repair mechanism for the cellular damage associated with aging could be used to restore the aged and hold off aging over and over again. It's more efficient and effective.

5) There is more than enough money in the world to have your cake and eat it - to fund both lines of research, metabolic tinkering and repair of damage. But this is not happening now. Successful fields have gravity - they attract new researchers and shape the course of science on a timescale measured in decades; without a great deal of work, the fight against aging will be metabolic manipulation and little else for the foreseeable future. That would leave us rather stranded twenty years from now.

6) Ergo, it is vitally important that we do more to create a counterbalance to the metabolic, slowing-aging research community - meaning the development of infrastructure dedicated to the repair of aging damage, rather than just slowing its accumulation. Without it, the results in terms of extended healthy life spans will peter out all too soon.

If you are new to the idea of aging as cellular damage - and the prospects for its repair - I strongly suggest you take some time to read over the website for Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS):

http://www.sens.org/

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/

Towards Better Blood (November 05 2006)
http://www.popsci.com/popsci/printerfriendly/science/9e367f36fca9e010vgnvcm1000004eecbccdrcrd.html
Improved blood has its upsides, as illustrated in Robert Frietas' view of respirocytes. While we're decades away from the era of advanced medical nanorobots, the creation of blood enhancers is a mainstream, going concern today. From Popular Science: "The life-giving liquid in our veins acts like a supply line for everything from nutrients to hormones to oxygen, even working double-time to regulate our blood pressure and fight infection. The manufactured substances, on the other hand, are one-trick ponies for oxygen delivery. But it's a trick they perform remarkably well - in the case of PFC-based substitutes, carrying oxygen at rates roughly 50 times that of our own blood." Once scientists have developed safe blood enhancers for treatment of traumatic injury, stroke, and the like, why not take that extra step and aim for safe permanent use as a preventative enhancement?

Elixir and Sirtris (November 05 2006)
http://news.bostonherald.com/localRegional/view.bg?articleid=165714
The Boston Herald characterizes the present efforts of companies attempting to manipulate the biochemistry behind calorie restriction: "this is hardly a Ponce de Leon-esque expedition. The Food and Drug Administration does not consider aging a condition that requires treatment." Which means that no venture capitalists will fund real longevity research, because treatments will not be approved, ergo no profit and no direct progress - what a waste! "So researchers are developing drugs to treat or prevent aging-related diseases like diabetes or obesity. The current explosion of anti-aging research dates to the 1930s when scientists discovered that dramatically reducing an animal's caloric intake will pile on extra years. ... Sirtris researchers have developed small molecules aimed at triggering the health-promoting effects from caloric restriction found in sirtuins, a class of enzymes. Elixir is also researching sirtuins, but it's seeking ways to treat diabetes and obesity by targeting ghrelin, a protein released in the stomach that regulates hunger and metabolic functions."

Controlling Neural Regeneration (November 04 2006)
http://www.sciencedaily.com/releases/2006/11/061103145955.htm
Scientists are making progress, step by step, in understanding the biochemical cues that can greatly enhance regeneration in our bodies and brains. From ScienceDaily: "insulin-like growth factor 1 (IGF-1) dramatically increases the in vitro growth of corticospinal motor neuron (CSMN) axons - projections that carry nerve impulses to the spinal motor neurons that connect to muscles ... [CSMN] die in motor neuron diseases like amyotrophic lateral sclerosis (ALS) ... The role of IGF-1 as a potent and specific enhancer of CSMN axon growth is highly relevant to our understanding of this critical population of neurons. These findings are a first step that may someday lead to ways of treating the neuronal degeneration of diseases like ALS, regenerating cells for the treatment of spinal cord injury, and to the potential replacement of neurons using precursors or 'neural stem cells.'"

Restoring Hardened Blood Vessels (November 04 2006)
http://www.eurekalert.org/pub_releases/2006-11/osu-lib110206.php
Blood vessels harden with age, causing a variety of dangerous conditions related to high blood pressure. This has been linked to advanced glycation endproducts (AGEs); here, EurekAlert reports on a different viewpoint: "The research, which was done in test tubes and animal models, needs to be confirmed in humans before it could form the basis for new therapies. But the fundamental findings reveal an important insight into how blood vessels change with age and lose much of their ability to relax, contract, and facilitate the circulation of blood in the body. ... Basically, we've learned that in older blood vessels, the cellular signaling process is breaking down. The vessels still have the ability to relax much as they did when they were younger, but they are not getting the message ... The laboratory studies were very compelling. We were able to make aging blood vessels behave as if they were young again ... This overall process, the researchers said, is linked to a low-grade, chronic inflammation that occurs with aging, in blood vessels and probably many other metabolic functions."

More On Zebra Fish Regeneration (November 03 2006)
http://www.sciam.com/print_version.cfm?articleID=AAFFD0D5-E7F2-99DF-3C4DEA936E6D7CD6
A number of researchers seek to bring the regenerative prowess of some lower animals into the realm of human medicine. Zebra fish are one candidate, if we can just understand how they do it. Scientific American reports that zebra fish "regenerate heart muscle in two synchronized steps. Within five days of removing about 20 percent of an adult zebra fish heart ventricle, undifferentiated progenitor cells begin to line the injured area and turn into cardiac muscle cells, which grow and divide, building new heart muscle. Meanwhile, developmental genes in the epicardium - a cell layer that surrounds the entire heart and influences embryonic heart development - switch on, activating the epicardial cells. Most of these cells form a new layer to cover the wound and the regenerating heart muscle, but some also create blood vessels for the growing muscle ... A growth factor signal orchestrates the two processes so that they converge to mend the zebra fish heart ... If the communication between the two cell types is blocked, the zebra fish heart starts to scar and cannot completely regenerate."

Attacking Sarcopenia (November 03 2006)
http://www.newscientist.com/article/dn10425-muscle-wasting-prevented-by-proteinblocker.html
(From the New Scientist). In addition to the possibility of a dietary therapy, scientists are looking at a genetic way around sarcopenia, or age-related muscle loss: "Throughout life the cells inside muscles undergo a constant build-up and break-down cycle. But in old age, muscle regeneration slows, leading to a loss of strength. A similar weakening occurs when muscles are not used. One way to stop this degeneration may be to modify the activity of key proteins inside muscle cells ... [the protein NF-Kappa-B] has a known role in inflammation ... Blocking the action of NF-Kappa-B in human muscle cells could help protect against muscle atrophy and promote tissue healing in people ... It would be unwise to try blocking NF-Kappa-B in humans with a simple pill [because] the protein has an important function in stimulating the immune system to fight off infection. Instead, researchers believe that a gene therapy approach might work to specifically block the protein in muscle cells alone."

Reminder: Living Well To 100 (November 02 2006)
http://www.genengnews.com/news/bnitem.aspx?name=8028456
By way of a reminder, the Living Well to 100 Conference starts next week in Boston, with a focus on inflammation in aging. "Increasing evidence supports the role of low-grade inflammation in many of the major diseases of aging, including cardiovascular disease, Alzheimer's disease, osteoporosis and cancer. The Living Well to 100 Conference brings together leading experts from throughout the world to consider how the information on inflammation may be used to extend healthy aging. Panels of experts will address the role of inflammation in the development of common chronic diseases; inherited and environmental factors that regulate the expression of inflammation; and how lifestyle and nutrition can help individuals mitigate their risk of developing the common diseases of aging that are exacerbated by the inflammatory process."

On Body Temperature and Longevity (November 02 2006)
http://www.forbes.com/forbeslife/health/feeds/hscout/2006/11/02/hscout535876.html
Via Forbes, another study attempting to tease out the mechanisms by which calorie restriction affects metabolism and health: "Lowering the core body temperature of mice let them live an average of 15 percent longer ... It was known in animals that calorie restriction is associated with reduction of the core body temperature. It was not known if temperature reduction was a consequence of calorie restriction or also contributed to its beneficial effects. ... The new study [shows] the latter to be true because the cooled-down mice lived longer even when they were allowed to eat as much as they wanted ... lowering body temperature does not prolong life span. It allows more mice to reach old age. ... Calorie restriction, by contrast, does extend life span."

Resveratrol In Mice (November 01 2006)
http://news.bbc.co.uk/2/hi/health/6105412.stm
From the BBC, news of a study of high dose resveratrol given to obese mice: "After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice. ... The 'healthspan' benefits we saw in the obese mice treated with resveratrol are positive clinical indicators and may mean we can stave of in humans age-related diseases such as type 2 diabetes, heart disease and cancer, but only time and more research will tell." Resveratrol appears to trigger the same or similar biochemical mechanisms as calorie restriction; studies have also been run in fish. Personally, I want to see the results of a high dose study in normally fed or calorie restricted mice. What does that do? Preventing the detrimental effects of obesity is a big deal in the wealthy, fattened regions of the world, but it isn't healthy life extension.

Reflecting on Calorie Restriction (November 01 2006)
http://ouroboros.wordpress.com/2006/10/30/does-caloric-restriction-extend-life-in-wild-mice/
As noted at Ouroboros, not all calorie restriction (CR) studies produce what appear to be positive results. As the first comment demonstrates, however, we non-scientists can't assume that something as conceptually simple as demonstrating extended healthy life span in mice is actually simple to carry out in practice. "[The results suggest] that something about the conditions in the lab - including possibly something about the CR regimen itself - was not well suited to these animals, thus causing early mortality unrelated to aging, but that aging was indeed slowed (which is what it means to say that 'CR works' in these animals), so that those animals that survived whatever killed their cohorts off early on enjoyed slowed aging and a resulting extension of maximum lifespan. ... When, famously, Weindruch and Walford revised the regimen by imposing CR gradually instead of all at once, and made sure that the diet was isonutrient outside of calories and carbs, a robust and proportional effect on lifespan was observed."

Yet Another Reason To Exercise (October 31 2006)
http://news.bbc.co.uk/2/hi/health/6098782.stm
Exercise, good diet and lifestyle choices like calorie restriction have an enormous impact on the health you'll have later in life. While it most likely won't extend your maximum possible life span, avoiding cutting your health and life span short increases your chances of living to see working anti-aging medicine capable of repairing the cellular damage that causes aging - and thus enjoying a life of good health for even longer than you expected. Via the BBC, here's another reason - amongst the many - to take better care of the health basics: "The study of people aged between 43 and 86 began in 1988 and they were assessed every five years. ... after taking into account other risk factors such as weight, blood fat levels and age, active participants were 70% less likely to develop [age-related macular degeneration, or AMD] than those who did little exercise. It also showed regular walkers were 30% less likely to get the disease." Healthy is as healthy does: it isn't rocket science.

Towards Tissue Engineered Livers (October 31 2006)
http://www.futurepundit.com/archives/003846.html
Randall Parker comments on a recent advance in engineering liver tissue: "We cannot build a fullsized liver yet. That will take about 10 years. But this is the first important step. We expect this to really take off in the next 18 months or so. ... Livers are relatively simpler things to grow than 3 dimensionally more complex structures such as hearts and kidneys. So I'm expecting we'll see replacement livers before replacement hearts or kidneys. ... For a number of types of organs replacement to treat cancer might end up saving more lives than replacement due to accidents and other diseases. Got pancreatic cancer? Replace it. Got kidney cancer? Replace it. ... If a cancer is still contained within a single organ then an excellent solution might some day be to just replace that whole organ. ... We can develop the technology to grow replacement parts for just about every part of the body and this can be accomplished within the lifetimes of most of the people reading this. So why aren't we trying much harder?"

A View of Rheumatoid Arthritis (October 30 2006)
http://www.eurekalert.org/pub_releases/2006-10/uomh-uso103006.php
(From EurekAlert!). Good, healthy science involves regular challenges to the present orthodoxy: "Why do nearly 95 percent of [rheumatoid arthritis or RA] patients have a common sequence of DNA, which scientists call a shared epitope, and why do patients with this DNA sequence have more severe forms of the disease than patients without it? ... Although the hypothesis that RA is an autoimmune disorder is widely accepted, there is no convincing evidence that it is correct. We see this same type of association [in] other diseases, which we know are not autoimmune diseases ... the shared epitope can trigger a signaling cascade that leads to increased production of nitric oxide [or NO] in other cells ... Overproduction of NO inhibits apoptosis - the natural process that leads to cell death. Resistance to apoptosis is a common trait found in cells lining the joints of RA patients, and is believed to lead to disease symptoms." To see quite different views - all backed up by good science - is an advance sign of more rapid progress towards a cure in the years ahead.

On Signing Up For Cryonics (October 30 2006)
http://www.betterhumans.com/blogs/simon/archive/2006/10/29/It_2700_s-official_3A00_-I_2700_m-signed-up-for-cryonics.aspx
Simon Smith of Betterhumans writes about the decision and process to sign up for cryonics: "I had already learned that cryonics is funded by life insurance, so, if you're young, you can get a pretty good deal on something that might save your life. You make low monthly payments and, should anything happen to you, the insurance goes to the cryonics organization responsible for your suspension. ... At the same time, I started the ball rolling with Alcor. They sent over some documents for me to complete, beginning with a declaration of my intent to be cryopreserved that would cover me legally - to a limited extent - while my life insurance and cryonics applications were being completed. And there's a reason for that. Getting cryonics life insurance and a cryonics membership is a lengthy process that's full of paperwork." There's room for improvement in there: a difficult sign up process is a real barrier to growth for any organization.

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