LONGEVITY MEME NEWSLETTER
November 19 2007
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.
- Reports From the 2007 Hillblom Foundation Meeting
- Bad Reasons to NOT Cure Aging
- The Value of Blood Vessels
- Latest Healthy Life Extension Headlines
REPORTS FROM THE 2007 HILLBLOM FOUNDATION MEETING
Aging researcher and science blogger Chris Patil has been on the meeting trail of late. The past week, he has posted reports from the 2007 Hillblom Foundation scientific meeting. The Larry L. Hillblom Foundation funds mainstream aging research taking place in California, including the lab of Cynthia Kenyon. You'll find links and quotes in this Fight Aging! post:
Along the way, Patil provides an excellent summary of the viewpoint and status of the presently dominant approach to longevity research - engineering greater longevity through genetic and metabolic manipulation:
"Given that genetic manipulations have revealed significant plasticity in the rate of aging, shouldn't we be able to discover drugs that phenocopy, simulate or even outstrip the effects of longevity-extending mutations? Thus far, early screens for both stress resistance and lifespan extension per se have generated several lead compounds that delay aging in yeast, worms and flies (and in at least one case, both species). Studies from multiple labs are beginning to converge, with the ultimate goal of testing multi-species hits in mouse models of aging and age-related diseases. In closing, Lithgow acknowledged that understanding of the mechanism of action of these compounds is lagging behind their discovery, in part because some of the most promising molecules have mystifyingly large numbers of candidate targets."
By now you probably all know that I consider metabolic engineering to slow the rate of cellular and biochemical damage of aging to be a poor, second best path in comparison to developing methods to repair that damage. A good summary as to why that is the case can be found here:
BAD REASONS TO NOT CURE AGING
Thanks to Methuselah Foundation volunteer Kevin Dewalt for posting his thoughts on the imperative to develop working repair technologies for aging, and the debates with those who oppose healthy life extension by knee-jerk reflex or principle:
"Ultimately we will figure out a way to undue this accumulated damage and prevent the diseases that will kill 90% of us. Whether we solve this problem in time to save the lives of our parents, us, our children, or our children's children depends on how difficult these problems ultimately prove to be and how hard we work to solve them.
"So with this foundation, it seems that we really don't have to continue the debate unless you believe that solving this problem will create other problems that are both (a) Worse and (b) Unsolvable.
Although this reality can seem surprising at first, that's basically it. If you strip away your emotional reactions to this issue - your cognitive dissonance - you'll see that these discussions are rather silly. Reversing aging solves a huge, horrible problem, and it makes every sense to pursue it as fast as we can to make sure that we and the people we love will be able to take advantage of it."
THE VALUE OF BLOOD VESSELS
One of the most important near-term hurdles for the development of complete organ reconstruction and other practical tissue engineering technologies - widely predicted to leave the labs for the clinic in the late 2010s - is the growth of blood vessels. If you can't sort out a correct and adequate blood vessel structure in tissue you are trying to grow, you will not succeed.
I recently noticed a popular science press article on a new approach to the problem that does a good job of explaining why the blood vessel issue is so important. Links and quotes can be found in this Fight Aging! post:
Following on from there, the post linked below looks at predictions from scientists such as Ellen Heber-Katz on timelines for the tissue engineering of complete organs on demand:
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!
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/
Mitochondria In FIRKO Mice (November 16 2007)
An interesting paper on one of the many varieties of engineered longevity in mice draws our attention to the links between mitochondrial function and healthy longevity: "Caloric restriction, leanness and decreased activity of insulin/insulin-like growth factor 1 (IGF-1) receptor signaling are associated with increased longevity in a wide range of organisms from Caenorhabditis elegans to humans. Fat-specific insulin receptor knock-out (FIRKO) mice represent an interesting dichotomy, with leanness and increased lifespan, despite normal or increased food intake. ... At the whole body level, FIRKO mice demonstrated an increase in basal metabolic rate and respiratory exchange ratio. Analysis of gene expression [revealed] persistently high expression of the nuclear-encoded mitochondrial genes involved in [the process of energy generation] ... Together, these data suggest that maintenance of mitochondrial activity and metabolic rates in adipose tissue may be important contributors to the increased lifespan of the FIRKO mouse." More evidence that how the machine runs is a lot more important than how fast the machine runs.
Keck Futures Initiative Conference on Healthspan (November 16 2007)
EurekAlert notes the latest Keck Futures Initiative conference: "This year's topic, 'The Future of the Human Healthspan: Demography, Evolution, Medicine and Bioengineering,' drew scientists, engineers, and medical researchers to discuss new interdisciplinary approaches in the fields of aging, longevity, and healthspan -- the period of a person's life during which they are generally healthy and free from serious or chronic illness. ... We have made great progress in extending the length of life and now must focus on the quality of those added years. We need to be bold and target innovative ways to help people sustain skills and abilities throughout extended lifetimes, assuring enhanced brain health as well as physical well-being." Which seems to be wrong thinking to me - we haven't made all that much of a foray into the realm of the possible when it comes to longevity through medicine, and we won't get much further if researchers stop thinking about pushing the boundaries in favor of patching up the results of aging as we see them today. If researchers instead focused on identifying and repairing the damage that causes aging, we'd never have to worry separately about healthspan - it'd sort itself out in the course of engineering longer, healthier lives.
Overachievements in Worm Longevity (November 15 2007)
Merely doubling healthy life span is old hat, last decade work now. We can engineer far better nematode worms than that: "C. elegans strains bearing homozygous nonsense mutations in the age-1 gene [produce] progeny that were thought to undergo obligatory developmental arrest. We now find that, after prolonged developmental times at 15-20 degrees C, they mature into extremely long-lived adults with near-normal feeding rates and motility. They survive to a median of 145-190 days at 20 degrees C, with nearly 10-fold extension of both median and maximum adult lifespan relative to [a] long-lived wild-type stock into which the null mutant was outcrossed. PI3K-null adults, although a little less thermotolerant, are considerably more resistant to oxidative and electrophilic stresses than worms bearing normal or less long-lived alleles." This and similar work forms an impressive set of technology demonstrations - there is no necessarily direct relevance to extending healthy human life span, but it certainly gets people fired up and excited.
Reminder: Video From SENS3 (November 15 2007)
Anne C. reminds us that a wide range of presentations on longevity research and related areas of scientific enquiry from the SENS3 conference this year are freely available. What to know what the future of medicine looks like? Educate yourself: "These SENS talks are a great example of longevity medicine as healthcare that will hopefully come to benefit everyone at some point. I'm quite interested in learning more about things like: the efficacy of cancer vaccines to prevent cancer in the elderly; the potential for virus modulation of cell death pathways; Immunological approaches for amyloid beta clearance toward Alzheimer's disease treatment. As you can see...no mooning over mythological notions of 'fountains of youth' here. Just good, solid investigative science geared toward helping mitigate problems like cancer in the elderly, cell death leading to other health issues, and Alzheimer's. And you definitely don't need to be a biologist in order to appreciate media like this -- all you really need is to be interested in the subject matter. ... With all the 'anti-aging fluff' making the rounds these days, it's nice to know that some people at least realize how complex (and important) the task of helping expand truly effective medicine to the elderly is."
A Closer Look at the Age-Damaged Immune System (November 14 2007)
This paper at Aging & Immunity takes a look at just a few detailed biochemical changes in the aging immune system (and the full PDF format paper is freely available). It's another perspective on inflammaging, and you'll notice that calorie restriction emerges again as a beneficial practice: "The mechanism explaining the increased disease susceptibility in aging is not well understood. CD8+ T cells are crucial in anti-viral and anti-tumor responses. Although the chemokine system plays a critical role in CD8+ T cell function, very little is known about the relationship between aging and the T cell chemokine system. ... we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression. Freshly isolated splenic CD8+ T cells from [old] mice were found to have higher CCR1, CCR2, CCR4, CCR5 and CXCR5, and lower CCR7 gene expression compared to their younger cohort. ... caloric restriction selectively prevents the loss of CD8+ T cell CCR7 gene expression in aging to the level that is seen in young CD8+ T cells. ... These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment." Receptors are a part of cellular biochemical programming, determining interaction and response. Change the balance of receptors and you change the capacity of the cell. Here, you're looking at the innermost workings of the grand machine we endeavor to understand, and then repair.
Mitochondrial Damage and Sarcopenia (November 14 2007)
Following up on work published last year, here's more on evidence for a link between accumulating damage to mitochondrial DNA and sarcopenia, age-related muscle loss: "Aging is associated with a progressive loss of skeletal muscle mass and strength and the mechanisms mediating these effects likely involve mitochondrial DNA (mtDNA) mutations, mitochondrial dysfunction and the activation of mitochondrial-mediated apoptosis. Because the mitochondrial genome is densely packed and close to the main generator of reactive oxygen species (ROS) in the cell, the electron transport chain (ETC), an important role for mtDNA mutations in aging has been proposed. Point mutations and deletions in mtDNA accumulate with age in a wide variety of tissues in mammals, including humans, and often coincide with significant tissue dysfunction. Here, we examine the evidence supporting a causative role for mtDNA mutations in aging and sarcopenia. We review experimental outcomes showing that mtDNA mutations, leading to mitochondrial dysfunction and possibly apoptosis, are causal to the process of sarcopenia."
On Centenarian Characteristics (November 13 2007)
You might find this PDF-format paper interesting. Nothing we haven't seen before in various studies, but it is a good reminder as to the cost of being overweight - it damages you, and shortens your life expectancy: "A random representative sample of 240 men born in 1887 and survived to age 100 was selected from the US Social Security Administration database. ... This allowed us to validate 171 cases of exceptional longevity, and obtain information on vital characteristics of male centenarians when they were young adults. ... It was found that the 'stout' body build (being in the heaviest 15% of population) was negatively associated with survival to age 100 years. Both farming and having large number of children (4+) at age 30 significantly increased the chances of exceptional longevity by 100-200%. The effects of immigration status, marital status, and body height on longevity were less important, and they were statistically insignificant in the studied data set. This study provides the first estimates of height, body build and other vital characteristics for the future centenarians at their young adult ages, and shows that detrimental effects of obesity may have an exceptionally long time range, and that obesity at young adult age (30 years) is predictive for almost three times lower chances of survival to age 100 years."
Expletive Deleted (November 13 2007)
Some very good points here, passed on by the Globe and Mail, whether or not it is 100% performance art: "Sipping Earl Grey tea at Ben Wicks, a lower-level Parliament Street hangout complete with paperback books and board games, they looked anything but nefarious as they described the Fuck Death Foundation, a non-profit charity they're launching over the next year to ultimately defeat mortality. Suspend your disbelief. Messieurs Wilkinson and Stewart are two of the city's most insightful people under 30 and their M.O. is not macabre, nor is it offensive ... Art can be so wishy-washy, so subjective. We wanted to have a quantifiable contribution to society ... An anonymous donor has covered initial administration and legal costs. In addition to assembling a board of directors, they hope to establish an operational model that will efficiently and effectively target parasitic and infectious disease, cardiovascular disease, cancer and AIDS. A Lightning Action Relief Fund will respond to global crisis situations. Over time, resources will be directed toward 'life extension sciences.' ... It's important to think about death. ... Unconsidered, life's not worth living." I'm all for covering all the memetic bases; best of luck to these fellows in creating more of the mindset whereby people are roused to shake their fists at aging and take action.
More Work on an Alzheimer's Vaccine (November 12 2007)
A range of different approaches are being taken to develop Alzheimer's vaccines, aiming to incite the immune system to step in and block various known biochemical mechanisms of the disease. From ScienceDaily: "Tang and his colleagues at OMRF previously had identified the cutting enzyme (known as memapsin 2) that creates the protein fragments believed to be the culprit behind Alzheimer's. In the current study, researchers used mice that had been genetically engineered to develop symptoms of Alzheimer's, then immunized the animals with memapsin 2. ... What we saw is that the mice immunized with memapsin 2 developed 35 percent fewer plaques than their non-vaccinated counterparts. Those immunized mice also performed better than control mice in tests designed to assess their cognitive function. ... Tang's work with memapsin 2 also has led to the creation of an experimental drug to treat Alzheimer's disease. That drug, which works by inhibiting the cutting enzyme, began human clinical trials in the summer of 2007."
Ouroboros on Restricting Inflammaging (November 12 2007)
Ouroboros notes some joining of dots on the mechanisms of inflammaging: "High levels of inflammatory cytokines in aging tissues have been implicated in immunological dysfunctions and frailty in the very old. What causes this age-related upregulation of inflammation? From Kim et al., we learn of a connection between two 'usual suspects' that might help explain the phenomenon. They propose that NF-kappaB (the no-brainer go-to candidate transcription factor for inflammatory responses) is activated by phosphorylation of FOXO (a key transcription factor in an evolutionarily ancient longevity assurance pathway), which increases with age. Furthermore, calorie restriction (CR) may protect the animal by decreasing overall levels of insulin (and insulin-like growth factor) signaling: less insulin/IGF means less FOXO phosphorylation, leading to reduced oxidative stress. This in turn reduces nuclear translocation of NF-kappaB and a relative diminution of inflammatory cytokine production." The body is a collection of complex, interacting systems with many points of linkage - this is just as true when the systems begin to fail as when they are running according to plan.