Longevity Meme Newsletter, February 04 2008

February 04 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.



- 50% Healthy Life Extension Demonstrated in Mice
- Journal of Internal Medicine, Special Issue on Aging
- On the Evolution of Extreme Longevity
- Discussion
- Latest Healthy Life Extension Headlines


Researchers have engineered mice that live healthy lives for 50% longer than their counterparts. It's another good demonstration of the fact that metabolic and genetic configurations exist that are quite similar to evolved configurations yet very superior in terms of health and life span. The results of evolution are not necessarily those best for the individual:


The research group merged two known mutations to obtain this result. First, a p53 mutation that reduces cancer but also speeds up the decline in stem cell activity and tissue maintenance. Secondly, a gene for enhanced telomerase levels that increases the risk of cancer and boosts stem cell activity and tissue maintenance with age. The net effect is less cancer and greater stem cell activity and tissue repair in older animals - and a healthy life extension greater than that produced by calorie restriction.

I'll make the fairly safe prediction that we'll be hearing much more about the p53/telomerase area of research in the years ahead.


The latest issue of the Journal of Internal Medicine focuses on aging, and a number of the papers are freely available. Some links and comments can be found in the following Fight Aging! post:


"Although the evolutionary theory of ageing is by now well established, there has continued to be a tendency to seek explanation of ageing in terms of some kind of adaptive genetic programme. The attractions of this concept are easily understood. First, ageing is phylogenetically a very widely distributed trait and in species where senescence occurs, it affects every individual that lives long enough to experience its adverse impacts on fertility and vitality. Secondly, there are clear genetic effects on longevity and this leads naturally to supposing that the relevant genes specify some kind of 'ageing clock'. In spite of these attractions, the programme theory, as a general explanation for ageing, is both logically and empirically unsound."


The natural world is replete with examples of extremely long-lived - and in some cases possibly ageless - animals and plants. To fit this into the evolutionary worldview is an ongoing challenge:


"How can evolution, biased to early reproductive success at all reasonable cost, produce such a species?"

Some potential answers from the scientific community can be found in the post above. The most important lesson to learn from an examination of the huge range in animal - even mammal - longevity is that it is possible to design better humans with the biotechnology of tomorrow. We could be longer lived, less diseased, less prone to aging. That is the driving goal behind much of the mainstream work in metabolism, genetics and aging these days. It'll be a long time in the making, however - a truly massive undertaking of great scope and complexity. While that great work is underway, we should devote more resources to the easier path to longevity: learning how to repair the humans we have now:



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!




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/

Bone Engineering Continues to Progress (February 01 2008)
Via Canada.com: scientists have "replaced a 65-year-old patient's upper jaw with a bone transplant cultivated from stem cells isolated from his own fatty tissue and grown inside his abdomen. ... [The researchers] isolated stem cells from the patient's fat and grew them for two weeks in a specially formulated nutritious soup that included the patient's own blood serum. In this case they identified and pulled out cells called mesenchymal stem cells -- immature cells than can give rise to bone, muscle or blood vessels. When they had enough cells to work with, they attached them to a scaffold made out of a calcium phosphate biomaterial and then put it inside the patient's abdomen to grow for nine months. The cells turned into a variety of tissues and even produced blood vessels, the researchers said. The block was later transplanted into the patient's head and connected to the skull bone using screws and microsurgery to connect arteries and veins to the vessels of the neck. The patient's upper jaw had previously been removed due to a benign tumor and he was unable to eat or speak without the use of a removable prosthesis."

The Thrust of Mainstream Alzheimer's Research (February 01 2008)
U.S. News gives a fair high-level summary of the main branches of Alzheimer's research at the present time: early diagnosis, immunotherapy and removing aggregates. From the article: "the closer science comes to a treatment for Alzheimer's, the more important early detection becomes. ... Promising techniques include MRIs used to show abnormal shrinking of the brain; pet scans to detect amyloid plaques in the brain or to spot patterns of glucose use associated with Alzheimer's; or spinal taps to look for abnormal concentrations of certain proteins in the cerebrospinal fluid during the early stages of Alzheimer's. ... Immunotherapy for Alzheimer's patients is just one of several new directions promising to transform the treatment of Alzheimer's ... We're at a juncture now where we're trying to make the transition from treating symptoms to disease-modifying treatments [that] hit at the cause of Alzheimer's. [A] whole new window is opening in terms of the approach to the disease. ... Other researchers, for example, are looking at drugs that target enzymes involved in the clumping of beta-amyloid proteins."

The Mitochondrial Nexus (January 31 2008)
A great paper in Cell (full text freely available for now) dives into the role of mitochondria in relation to aging, calorie restriction (CR) and sirtuins: "CR can exert a positive effect on mitochondria, boosting mitochondrial activity and hence providing at least some of the salutary effects of CR. ... CR and sirtuins upregulate the activity of mitochondria in different organisms. ... There is ample evidence that damage to mitochondria increases progressively with age. This has been observed in the form of the accumulation of mutations in mitochondrial DNA and a decline in the activity of mitochondrial enzymes and components of the electron transport chain. ... A higher pool of functional mitochondria may ameliorate tissue damage simply by buffering [cells] against the gradual decline in the ability to produce energy as mitochondria become damaged during aging. One may well wonder why mitochondrial number is not normally set to a higher level during ad libitum feeding to forestall this decline. It is important to remember that aging occurs postreproductively and is nonadaptive. Thus, under normal conditions, mitochondrial number and function will only fall sway to selective pressure until the reproductive period has been completed. ... By this logic, CR and perhaps other stressors may impose a new selective landscape in which robust somatic maintenance, rather than reproduction, is now at a premium and mitochondrial biogenesis favored."

It's Wonderful, But Let More People Die First (January 31 2008)
A look at one particular type of objection to healthy life extension in this New American Media piece: the person who agrees with the goal of defeating age-related suffering and death, but nonetheless feels that even wonderfully positive change must be slow and socialized - discussed, debated, funneled through the polical and regulatory sausage machine. "It deserves a long and wide-ranging effort of serious deliberation - not just debates, which rarely change anybody's mind, but dialogues in which people actually listen to one another and consider deeply all the issues and scenarios. Such an effort will take time and money, but certainly no more than it will take to figure out how to turn old geezers into young geezers. It could run concurrently with life-extension research, and it would inevitably deepen our understanding of the complexities of human life." To which I usually respond: "well then, just how many people - at the rate of 100,000 lives lost each day - are you willing to condemn to death by aging for the sake of your delicate sensibilities?" There is no other moral choice beyond as much freedom of research as possible, and as great a speed as can be mustered.

Exploring the Biochemistry of Calorie Restriction (January 30 2008)
Researchers continue to make solid progress in detailing the biochemical mechanisms by which calorie restriction extends healthy life: "Calorie restriction (CR), the only non-genetic intervention known to slow aging and extend life span in organisms ranging from yeast to mice, has been linked to the down-regulation of Tor, Akt, and Ras signaling. In this study, we demonstrate that the serine/threonine kinase Rim15 is required for yeast chronological life span extension caused [by] calorie restriction. ... Deletion of stress resistance transcription factors Gis1 and Msn2/4, which are positively regulated by Rim15, also caused a major although not complete reversion of the effect of calorie restriction on life span. ... Notably, the anti-aging effect caused by the inactivation of both pathways is much more potent than that caused by CR." Enumerating the required parts of the chain, one by one, is an early step in the process of building a full understanding - and then reproducing and improving upon natural longevity-inducing biochemistry. Interestingly, Rim15 is also required for the recently demonstrated set of genetic tweaks that boost yeast life-span ten-fold - even though that did not involve calorie restriction.

A Few More Short Aubrey de Grey Videos (January 30 2008)
It seems there is a whole business ecosystem out there revolving around very short, single-topic educational video clips. In addition to the VideoJug question and answer sessions with biomedical gerontologist Aubrey de Grey - collected on the Methuselah Foundation website - you can find more of the same at Big Think. From the perspective of an advocate, I certainly see the value of collected short answers to many pertinent questions about healthy life extension, the science of repairing aging, and plans to develop real anti-aging therapies. It remains to be seen whether any of these businesses find enough profit in this venture to build a sustaining architecture dedicated to this sort of educational content.

Thoughts on Stem Cell Banking (January 29 2008)
As this New York Times article points out, the most obvious reason for not banking your stem cells - now that you can - is that it seems likely science will quickly progress far past their utility: "some experts say consumers should think twice before spending hundreds or thousands of dollars on such services, because it is not clear how useful such cells will be. ... Some people buying the services say there is little to lose from doing so except money, even if the chance that the cells will be needed or useful is slim. ... Scientists say it is quite unlikely a person will ever need such cells. And the technology could change so much that cells stored now may not be needed if a person falls ill in 10 or 20 years. Recently, scientists found a way to turn skin cells into cells that behave like embryonic stem cells. That might allow a person of any age to have customized tissue created on the spot." So it's a rational decision of risk, reward and chance. How long before aging catches up with you, and how long before science masters the biology of regeneration with no need for those stem cells from your past history?

On the Way to Biomechanical Sight (January 29 2008)
We live in an era close to artificial eyes, to regrowth of complex organs, and to a full melding of technology and biology. So you'll see things like this on the way to where we're going: "The technique could enable sufferers of retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy to see. In the advanced stages, retinas with these disorders can no longer detect light, which means they no longer have usable rods and cones, but all their remaining neurons, such as the ganglion cells, survive. This raises the possibility that a retinal prosthetic could bypass the diseased tissue and stimulate the remaining healthy cells. ... A discreet prosthetic in front of the patient's eyes would capture images with a camera and process the information. It would then stimulate ganglion cells by outputting a series of bright, intense light spots to them. ... With gene therapy, a patient's entire population of ganglion cells could be turned into light-sensitive neurons. ... The prosthetic will also use retinal algorithms to replace the visual processing lost in the diseased retinal tissue. ... So essentially we've put all the engineering outside the eye, and the device will attempt to talk to the retinal ganglion cells through optical communication."

Groundwork For Stem Cells Versus Stroke Damage (January 28 2008)
The groundwork continues to be laid for the use of autologous stem cell therapies to regenerate more varied types of damage in the aged. Via EurekAlert!: bone marrow stromal cells (BMSCs) "were injected into animals 24 hours following [a stroke] ... researchers found that within seven days of the injection the BMSCs had migrated through the region of the middle cerebral artery into the scar area and border zone of the ischemic region. ... We evaluated vascular density in the ischemic region in all animals seven days after cell transplantation. The animals exhibited significant reductions in scar size and cell death and improvements in neurological function when compared to controls that received no BMSCs ... the intravenous delivery of bone marrow-derived cells may enhance tissue repair and, in turn, functional recovery after a stroke. While the potential mechanisms for this recovery are unclear, among the possibilities are that the brain microenvironment early on following a stroke may mimic brain development. Subsequent elevated levels of growth factors might enhance homing of BMSCs to the injured area and induce cell proliferation." Greatly enhanced regeneration through manipulation of stem cells and cellular environments will be commonplace a decade from now.

Don't Just Sit There, Aging Away (January 28 2008)
From EurekAlert!, more on the aging-exercise connection: "Individuals who are physically active during their leisure time appear to be biologically younger than those with sedentary lifestyles ... Regular exercisers have lower rates of cardiovascular disease, type 2 diabetes, cancer, high blood pressure, obesity and osteoporosis ... Inactivity may diminish life expectancy not only by predisposing to aging-related diseases but also because it may influence the aging process itself ... Men and women who were less physically active in their leisure time had shorter leukocyte telomeres than those who were more active .... Oxidative stress - damage caused to cells by exposure to oxygen - and inflammation are likely mechanisms by which sedentary lifestyles shorten telomeres, the authors suggest. In addition, perceived stress levels have been linked to telomere length. Physical activity may reduce psychological stress, thus mitigating its effect on telomeres and the aging process." If you want to maximize your chances of living into the era of radical life extension medicine, it pays to take care of the health basics.



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