Longevity Meme Newsletter, April 28 2008

April 28 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.



- Body Temperature and Longevity
- Sirtris Pharmaceuticals Acquired
- Discussion
- Latest Healthy Life Extension Headlines


Why is it that lower body temperature extends longevity (in mice, at least)? Lower body temperature is a feature of calorie restriction, but also extends longevity if engineered through other regulatory processes, such as altering the workings of the hypothalamus. Theories abound, but definitive answers are still in the years ahead:


"Some researchers would like to pin temperature-dependent longevity on the rate of chemical reactions in the body (reaction speeds generally being proportional to temperature), but I suspect that's too simplistic. An alteration in the rate at which mitochondrial processes generate damaging free radicals sounds more plausible, driven by some temperature-sensitive signaling and control process."


The natural progression of interest in calorie restriction biochemistry - and the calorie restriction mimetic drugs that are resulting - continues with the acquisition of Sirtris Pharmaceuticals by GlaxoSmithKline. Sirtris is largely focused on sirtuins, just one part of the regulatory and signaling systems affected by calorie restriction:


The consensus amongst industry observers seems to be that this one more step in an ongoing shift towards legitimacy for longevity research, but that regulation is still the biggest hurdle to development. If the FDA will not approve your longevity therapy - which it presently will not, as it doesn't consider aging a disease - then there will be no funding for commercial efforts, and no attempts to turn basic longevity science into practical applications for extending healthy life. Instead you'll see what is presently taking place at Sirtris, which is to turn to whatever application the FDA will approve; diabetes treatments in this case.

It is frustrating to imagine what could already be happening if the FDA did not exist - many billions of dollars in venture capital invested in a vast range of promising science aimed at repairing the damage of aging and achieving true rejuvenation, rather than the hundreds of millions of dollars today aimed only at slowing the progress of late-stage results of aging.


The highlights and headlines from the past week follow below.

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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/

More Thoughts on PEPCK-Cmus Mouse Longevity (April 25 2008)
Dry wit from Ouroboros on the very long-lived PEPCK-Cmus mice: "It's become reflexive to ask whether a long-lived mutant is living longer because it's calorie-restricted for some reason, incidental to the main phenotype conferred by the mutation, but this is not the case here: In order to preserve their enviable bods, PEPCK-Cmus mice eat 60% more than controls - so they're not extending their lifespan by dieting. If anything, they're anti-dieting: their increased metabolic efficiency means they’re harvesting more calories per gram of carb or fat than normal animals. No word yet on what happens if you do try to calorie-restrict them; I can imagine it going either way but am holding out hope for tiny explosions. ... The PEPCK-Cmus seem to have it all: great bodies, long lives, extended reproductive and sexual lifespans, and no need to limit their appetites. The down side? Apparently, they are complete assholes: the mutants are aggressive and hyperactive, traits heretofore unheard-of among muscular, fit humans (and, indeed, in the field of biogerontology)."

Caplan on Arguing Against Longevity (April 25 2008)
MSNBC is running an op-ed by Arthur Caplan on a few of the more common knee-jerk objections to engineering greater human longevity: "arguments that we should not live a lot longer because we will grow decrepit are simply silly. No one proposes that we spend a lot of money on biomedical research to pursue a longer life of decrepitude and suffering. The idea behind radical life extension is that we live a decent quality of life for a lot longer. If all that is in store is frailty and mental decline, then the debate is over before it starts. But that is not what the debate is really about. ... As for violating some natural limit if we live a lot longer - what limit? We have already doubled our lifespan since the days of the Hittites, Israelites, Greeks, Babylonians and Egyptians, all of whom were lucky to make it to 35. Are we already living unnatural, and thus immoral, lifespans? ... Evolution cares not a whit how long you or I live, only that we survive to reproduce. There is no such thing as a 'natural' lifespan - only what we can do with agriculture, engineering, medicine and public health."

Why the Germline-Longevity Link? (April 24 2008)
If you eliminate germline stem cells in flies and nematode worms, they live 20-50% longer. From ScienceDaily, an explanation of the biochemistry: "When reproduction is delayed, animals live longer. Why? Our research suggests that signals from the reproductive system can regulate aging in animals - including, possibly, humans ... speculated that these flies might live longer because they are insensitive to the effects of insulin. ... animals such as flies, worms and mice live longer when they produce or receive less insulin. ... [but] when germline cells were eliminated, and flies lived longer, insulin-producing cells in the fly brain actually make more - not less - insulin. ... How can flies be longer-lived when they're making more of a life-shortening hormone? ... Even though the brains were making more insulin, the bodies were responding as if there was less insulin present. ... In reaction to the flies' brains boosting insulin production, the insects' gonads - their ovaries or testes - produce a protein that acts like a sponge. This protein binds to the insulin and blocks its signals throughout the body. So the flies respond as if there is low, not high, insulin circulation inside their bodies."

Investigating AMPK Signaling (April 24 2008)
AMPK is one of the more important regulatory components in our metabolic machinery, activated by lower energy intake - such as calorie restriction - and diminishing with age. As such, AMPK signaling changes are prime target for investigation. From EurekAlert!: "when cells are kept hungry in a culture dish, a watchdog enzyme called AMPK jumps into action and attaches a chemical phosphate group to a target protein named raptor. As a result, raptor, whose job is to cradle a growth-promoting protein called mTOR, is disabled, inactivating mTOR and halting cell division. Cells then safely switch into energy conservation mode until plentiful times return. ... Simply the most rudimentary information that any cell needs is to know whether there is food around - that's what AMPK senses. If there is not, you need to turn off factors that make cells grow." mTOR is another party of interest for calorie restriction research - is there a good way to achieve the beneficial health and longevity benefits of calorie restriction by directly manipulating the controls our biochemistry?

SAGE Crossroads Rises From the Dead (April 23 2008)
What should I find in my in-box today, but an email from SAGE Crossroads, a professional site on aging science and policy (far too much policy for my taste) that ceased updating a while back. It seems they've risen from the dead this year, and are once again putting new content online in the form of Sagecast videos - see the right hand side on their home page: "Many have argued that when it comes to advances from longevity research - the science is there, but the policy's not. Dr. Richard Miller discusses policy barriers and solutions including insight into the issues faced by FDA, CMS, and NIH when it comes to longevity science. ... In addition to the regulatory and other policy hurdles that longevity science must face, the 'politics' also play a role. Dr. Robert Butler chatted with SAGE Crossroads about the environment, attitudes, and perceptions that challenge the translation of longevity science." For my part, I suspect that the spheres of policy and government research institutions are the last places to look for the signs of rapid, revolutionary progress in enhancing human longevity.

Growing New Heart Cells (April 23 2008)
Researchers continue to work on the infrastructure for practical tissue engineering, here succeeding in "growing large numbers of stem cells from adult human hearts into new heart muscle cells. A breakthrough in stem cell research. Until now, it was necessary to use embryonic stem cells to make this happen. ... The cells grew into fully developed heart muscle cells that contract rhythmically, respond to electrical activity, and react to adrenaline. ... We've got complete control of this process, and that's unique. We're able to make heart muscle cells in unprecedented quantities, and on top of it they're all the same. This is good news in terms of treatment, as well as for scientific research and testing of potentially new drugs. ... Stem cells from the hearts of patients with genetic heart defects can be grown into heart muscle cells in the lab. Researchers can then study the cells responsible for the condition straight away. They can also be used to test new medicines. This could mean that research into genetic heart conditions can move forward at a much faster pace. In the future, new heart muscle cells can likely be used to repair heart tissue damaged during a heart attack."

The Trailing Indicators (April 22 2008)
Judging by this MSNBC article, it takes three to four years for new information to percolate into the mass media to the point at which it appears in general interest pieces on a particular topic. So this article on longevity science looks something like a refugee from late 2004, but I'll take it as a sign of progress that this is the worst thing I can find to say about it. "Public imagination has been sparked by researchers such as Aubrey de Grey, the British scientist who claims that aging is an 'engineering problem' that can be solved by identifying basic causes of aging and creating nuts-and-bolts medical and biomedical solutions. These may include growing new organs or tissues for use in aging bodies, or other techniques promised by the burgeoning field of regenerative medicine. But some scientists who study the underlying causes of aging say such benefits aren't likely to extend lifespan in the near future. 'It's easy to say that aging is an engineering problem, but we're pretty elaborate pieces of engineering,' says longevity researcher Brian Kennedy ... Nonetheless, leading anti-aging researchers are pursuing several approaches that they hope may one day extend lifespan." The article goes on to mention some of the better-known fields, such as research into the biochemistry of calorie restriction.

Surveying the "Anti-Aging" Snake Oil (April 22 2008)
MSNBC looks at the "anti-aging" marketplace, as busy selling snake oil and muddying the water as ever: "dozens of businesses set up displays to market everything from horny goat weed dietary supplements to wands containing dirt that supposedly align water molecules so the H2O will get into your cells. Many of the products and services attempt to capitalize on recent science buzzwords. Terms like 'stem cells' [were] flung about, but mostly it was a case of putting old wine in new skins. 'ADULT STEM CELLS are the BEST-KEPT SECRET in today's wellness...' boasted a flyer for a dietary supplement ... Take it and increase 'the number of circulating stem cells in your body.' Not only can it 'replace diseased cells with healthy cells' and provide 'anti-inflammatory and immune system support' but also give users 'mental clarity and mood elevation.' But the products are really just a repackaging of a supplement that has been marketed aggressively since the 1980s, a form of blue-green algae called aphanizomenon flos-aquae. The science behind the claimed benefits for aphanizomenon is slight - whether the claim is for immune boosting as it was 20 years ago, or stem-cell enhancement as it is today. In fact, there has long been concern about the presence of toxins in blue-green algae products, though you wouldn't know it from the marketers at the trade show." The level of utter nonsense and falsehood in the marketplace is quite amazing at times.

A Doubling of Mouse Lifespan? (April 21 2008)
You might recall the PEPCK-Cmus mice reported last year: great health and lots of positive improvements in their metabolic biochemistry. They eat hugely, don't put on weight, are very active, and live long. That last item is starting to look impressive indeed: "A second surprising result was the apparent extended longevity of the PEPCK-Cmus mice; they lived almost 2 years longer than the controls and had normal litters of pups at 30-35 months of age (most mice stop being reproductively active at 12-18 months). We use the word 'apparent' because we have not as yet carried out a detailed aging study, involving multiple mice, which are followed at regular intervals over their lifetime; this type of study is currently in underway in our laboratory so hopefully we will be able to state unequivocally that the PEPCK-Cmus mice do live longer than controls." The present longevity record holder is a touch under 5 years for growth hormone manipulation, but this PEPCK-Cmus method leads to much more robust mice. The underlying mechanism is up for debate - it seems to be a polar opposite of longevity induced by calorie restriction biochemistry.

A Thoughtful Tribute to the Work of Aubrey de Grey (April 21 2008)
From Ouroboros yesterday, and well said: "Forty-five years ago, Aubrey David Nicholas Jasper de Grey was brought into the world. Today is his birthday, and it seems appropriate to briefly reflect on Aubrey's achievements to date and what he represents to biogerontology. At times brilliant, at times exasperating, Aubrey is unquestionably the world's most energetic popularizer of the idea that there is something we can do about aging - and not just a little something, mind you, but a very big something: we can end it, once and for all. In particular, he argues, we can take an engineer's approach to reversing or repairing several types of damage that characterize aging, and thereby eliminate the process of aging itself. ... it is good and right that we appreciate Aubrey for his energetic efforts in pushing a radical idea - that aging might someday be vanquished - out of the fringes and into the mainstream of modern biological thinking. Despite his differences with individual scientists (and sometimes with large groups of them, waving torches) he remains biogerontology's most prominent popularizer, and therefore in some sense the field's biggest fan." If Aubrey de Grey didn't exist, it would be necessary to invent him.



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