Longevity Meme Newsletter, June 04 2007

June 04 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.



- Aubrey de Grey's Google TechTalk Presentation
- The Invisible Cost of Regulation
- Discussion
- Latest Healthy Life Extension Headlines


Aubrey de Grey's recent presentation for the Google TechTalk series is now available at Google Video:


It's longer than many of de Grey's other presentations, and delves more deeply into the details of presently ongoing research aimed at repairing the damage of aging, as well as the science behind the Strategies for Engineered Negligible Research.



The cost of regulation of medical research and development is large indeed, measured in lives, and yet invisible to most:


"Drug discovery and medical research is in fact no more inherently costly or time-consuming than research into new forms of computer hardware - a field that is just as exciting at this present time. But medical research and development is made costly by the heavy boot of regulation for the sake of regulation: an institution of rules and rule-makers that has come to stand for nothing beyond its own self-propagation.

"If anything is to be the death of us in this era of potential and revolution in biotechnology, it will be that regulation scared away the innovators, suppressed the discoveries that might have been, and kept disruptive, effective new technologies away from the marketplace for years past their time. When progress is made costly, progress becomes slow - but worse, an entire range of invention and endeavor simply vanishes, priced out of existence.

"But most people can't see the invisible cost - the cost of things that might have been. Most people suffer a great failure of the imagination when it comes to anything the government has a hand in; they can't imagine it any other way, even when presented with thriving examples from other industries. Medicine could be as dynamic, inventive and productive as the computer hardware industry, or the fashion industry. But it is not, and so we will suffer because progress will be slow and the delivery of goods funneled through organizations so regulated that their employees and owners have no incentive to do a good job."

Remember that most of you folk live in regions where unaccountable, unelected career bureaucrats decide what forms of medicine you can access, how medicine can be provided to you, and what forms of medicine can be researched. They have no incentive at all to reduce the level of harm their decisions cause both to present health and future progress. These government employees have declared aging to be natural, not a disease, and will not approve any potential, plausible therapy aimed at slowing or reversing aging. That is just the tip of the iceberg, however; the closer you look, the worse it appears.


The slow choking of medical progress is the natural consequence of centralized, unaccountable control. Those of you old enough to recall the Soviet Union know where that road leads in the end - poverty and stagnation. Is this really the launching pad for a future you'd like to participate in?



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!


Founder, Longevity Meme



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/

Retiring the Weekends (June 03 2007)
Going forward, I've decided to undertake the experiment of retiring weekend posting here at the Longevity Meme and over at Fight Aging!. This is something of a "less is more" decision: posts can always be better or more relevant to the topic at hand - the hows and wherefores of healthy life extension - than the stock standard of a link, comment and related thoughts. Taking a couple of days out of the schedule will help in that regard. I do not believe that this will significantly impact the contribution of Fight Aging! and the Longevity Meme to the online conversation about healthy life extension and longevity science - five times a week is plenty enough to talk up a storm. The time saved by dropping two days can be profitably diverted to other matters. I'm far past time on bringing the Methuselah Foundation blog up to spec with the rest of the Foundation site redesign, for example, and the Longevity Meme newsletter requires some technical attention behind the scenes. The list is always a long one.

Working on Telomerase Gene Therapy (June 02 2007)
A number of groups are working on gene therapies for aging and age-related disease based on manipulation of telomere length. Here is some insight into what that work looks like: "Degeneration of the intervertebral disc is an age-related condition in which cells responsible for the maintenance and health of the disc deteriorate with age. Telomerase can extend the cellular lifespan and function of other musculoskeletal tissues, such as the heart, bones, and connective tissues. Therefore, extension of the cellular lifespan and matrix production of intervertebral disc cells may have the potential to delay the degeneration process. ... nucleus pulposus cells were lipofectamine transfected in vitro with a human telomerase reverse transcriptase (hTERT) expression construct ... hTERT transfection enabled a 50% extension in mean cellular lifespan and prolonged matrix production of collagen 1 and 2 for more than 282 days. ... Telomerase can extend the cellular lifespan of nucleus pulposus cells and prolong the production of extracellular matrix. Safety is still unresolved, as karyotypic instability was detected but no loss of contact inhibition, mitogen dependency, or G1-cell cycle checkpoint control was evident." That last meaning it is unclear as to whether the risk of cancer is increased by this process.

Systems Biology and Understanding Cells (June 02 2007)
The NYAS looks at efforts to better understand our cells - this is key to the most important potential advances in medicine foreseen for the decades ahead, such as extending the healthy human life span. "Thinking of the cell as a factory and biologists as engineers, [a] geneticist might unscrew every pipe inside the factory, one at a time for controlled experiments, of course, and determine the effect that the change has on the factory's operation, or the cell's function. A structural biologist might focus on the shape and size of one particular valve and try to determine how it contributes to the cell-factory's overall functioning. A biochemist would grind up the whole factory and then try to purify and analyze each of its various parts. ... But as scientists and engineers well know, a strictly reductionist view limits one's ability to see the big picture. A zoom-in-zoom-out process is often necessary to make significant progress in the quest for knowledge. This is the perspective of a systems biologist, who seeks to model the mechanistic details of the inner workings of a cell without losing sight of the larger experimental picture. These are the factory's engineers who create blueprints of the building, annotated in excruciating detail with its key industrial processes, and then step back to admire the plans as a whole."

Research From the Old School (June 01 2007)
The research noted by Newswise here does not strike me as the future of longevity science: "Aspirin didn't pan out. Neither did two other potential anti-aging agents. But a synthetic derivative of a pungent desert shrub is now a front-runner in ongoing animal experiments to find out if certain chemicals, known to inhibit inflammation, cancer and other destructive processes, can boost the odds of living longer. ... scientist Richard A. Miller reports early results from a mouse study his lab and two others are conducting for the National Institute on Aging. The study, now in its fourth year, will test as many as two dozen possible anti-aging agents in animals in the next five years." Discovering potentially interesting mechanisms in metabolism by testing ingestion of various chemicals is an inefficient journey along an inefficient path. We can do better than this, both in our methodology for identifying interesting mechanisms, and in the methods by which we attempt to extend healthy life span. Crude manipulations with chemicals from the environment can never hold a candle to the directed use of biotechnology to identify and repair the damage of aging. Which would you prefer scientists worked on for the next couple of decades?

Neural Regeneration Via Stem Cells (June 01 2007)
Picking their test cases carefully, researchers are making progress towards a technology base for repairing nerves and brain cells: "Rats paralyzed due to loss of blood flow to the spine returned to near normal ambulatory function six weeks after receiving grafts of human spinal stem cells (hSSCs) ... We demonstrated that when damage has occurred due to a loss of blood flow to the spine's neural cells, by grafting human neural stem cells directly into the spinal cord we can achieve a progressive recovery of motor function ... Three of the nine rats injected with hSSCs returned to walking at six weeks, and three others had improved mobility in all lower extremity joints. All nine animals grafted with hSSCs achieved significantly better motor scores than those in the control group, and showed a consistent presence of transplanted cells in the spinal area. In all the rats grafted with the stem cells, the majority of transplanted human spinal stem cells survived and became mature neurons ... Other human stem cell transplants in the spinal cord have focused on repairing the myelin-forming cells. In this study, we succeeded at reconstructing the neural circuitry, which had not been done before."

Brightening Prospects For Muscle Regeneration (May 31 2007)
Continued signs of progress in regenerative science from EurekAlert!: "so-called satellite cells in muscle actually include a mix of cells already committed to their muscular fate and others that behave like more versatile stem cells. The cells had widely been considered by scientists as a homogeneous population of dedicated muscle progenitors. Moreover, [researchers] showed that injection of the 'satellite stem cells' into the muscles of mice successfully replenished the animals' regenerative reservoir of cells. ... We've found that there are two types of satellite cell - 90% that are already committed to becoming muscle and another 10% with characteristics normally attributed to stem cells. It's not been shown yet, but these muscle stem cells might even have the capacity to make other tissues, such as bone and fat ... We've also shown that these satellite stem cells, when transplanted into muscle, can repopulate the regenerative cell niche. This is a very significant advance in our understanding of satellite cell biology that will require us to rethink decades of research. It also opens new avenues for therapeutic treatment of muscular diseases."

Aging Stem Cells and What Can Be Done (May 31 2007)
Why do the regenerative capacities of stem cells diminish with age, and what can be done about it? This paper looks at some of the specific mechanisms as they work to suppress young transplanted cells: "aged differentiated [stem cell] niches dominantly inhibit [certain important gene expression] in activated satellite cells, and reduce proliferation and myogenic differentiation of both embryonic [hESCs] and tissue-specific adult stem cells (ASCs). ... the ability of hESCs, and the more differentiated myogenic ASCs to contribute to tissue repair in the old will be greatly restricted due to the conserved inhibitory influence of aged differentiated niches. ... hESC-derived factors enhance the regenerative potential of both young and, importantly, aged muscle stem cells in vitro and in vivo; thus, suggesting that the regenerative outcome of stem cell-based replacement therapies will be determined by a balance between negative influences of aged tissues on transplanted cells and positive effects of embryonic cells on the endogenous regenerative capacity. Comprehensively, this work points toward novel venues for in situ restoration of tissue repair in the old and identifies critical determinants of successful cell-replacement therapies for aged degenerating organs."

Disposing of Disposable Soma Theory (May 30 2007)
"According to the disposable soma theory, a cost for reproduction could exist in human beings and other species and, thus, longevity could decrease when women have a higher number of children. The purpose of this article is to review the evidence in populations living or not living under natural fertility conditions, i.e. when fertility is near its biological maximum. The results indicate that in natural fertility conditions longevity does not decrease when the number of children increases but, in modern populations, mortality could slightly increase when women have more than 5 children. Complete data for these modern cohorts will tell us, one day, whether these results are still observed when the variable of interest is longevity and not only mortality." The disposable soma theory of aging, arising from evolutionary considerations, has moved through a number of interations to its present form. It is not highly regarded in comparison to other theories, largely because of this sort of evidence. The model of the body as a self-repairing machine subject to an accumulation of characteristic types of damage it cannot repair far better fits the observed facts.

Skeptical on Sir2 (May 30 2007)
As noted at Ouroboros, there's still plenty to debate in calorie restriction science. Well-funded companies are developing therapies and human studies have been taking place for years, but discussions continue on the basic research in lesser species: "In the last decade, research into the molecular determinants of aging has progressed rapidly and much of this progress can be attributed to studies in invertebrate eukaryotic model organisms. Of these, single-celled yeast is the least complicated and most amenable to genetic and molecular manipulations. ... Activation of Sir2-family proteins in response to calorie restriction (CR) has been proposed as an evolutionarily conserved mechanism for life span extension. This idea has been called into question with the discovery that Sir2-family proteins are not required for life span extension from CR in yeast. ... Several specific cases where the Sir2 model of CR is inconsistent with experimental data are noted. These shortcomings must be considered along with evidence supporting a role for Sir2 in CR in order to fully evaluate the validity of this model." A number of other possible candidate genes and proteins have been put forward in the past year; as scientists continue to investigate, the situation will become more clear.

Thoughts On Exercise and Gene Profiles (May 29 2007)
Randall Parker comments on recent research on the biochemical effects of exercise on aging tissue: "The reversal isn't complete. Aged muscles are still weaker and their gene expression patterns are still different than youthful patterns. We need to know why the aged muscles do not fully regain youthful strength when exercised. ... The resistance training exercise does not simply substitute for a lower level of exercise in the elderly. Younger control subjects who did not exercise much had youthful gene expression profiles even though they didn't exercise much. ... We need a gene therapy delivery mechanism that can deliver replacement mitochondrial DNA (mtDNA) into muscle tissues. Such a therapy would help us answer the question of whether accumulated mtDNA damage is a substantial cause of muscle aging. I hope the answer is 'yes' because methods to replace mtDNA will be much easier to develop than methods to replace nuclear DNA (i.e. the DNA in chromosomes in the nucleus of cells). Why the difference in difficulty? The nucleus contains over 2.9 billion base pairs of DNA whereas the mtDNA contains about 15,000 base pairs. So development of methods to deliver replacement mtDNA should be a relatively simpler task."

Yet More Harm From Cytomegalovirus (May 29 2007)
(From EurekAlert!). Adding insult to injury: as if the destruction of your immune system over the years was not enough, cytomegalovirus also causes further direct harm to your body: "Atherosclerosis is the main cause of morbidity and mortality worldwide. ... Recently inflammation and infectious agents have been shown to play an important role in the onset of acute cardiovascular events. ... Cytomegalovirus infection can be responsible of the initial vascular lesions typical of the atherosclerotic process. The mechanism involved in the vascular lesion is of autoimmune origin: antibodies directed against particular proteins of the virus are able to bind molecules expressed on the surface of the cells that line the arterial walls (endothelial cells) and to cause their death (apoptosis) through a mechanism called 'molecular mimicry.' ... This new study therefore confirms that antibodies directed against Cytomegalovirus-derived proteins purified from patients with coronary artery disease induce endothelial cells damage and support the hypothesis that virus infection plays a crucial role in mediating the atherosclerotic process."

Know the Opposition (May 28 2007)
Daniel Callahan is the deathist's deathist, working away to equate bioethics with suppression of healthy life extension technology and glorification of death and suffering. He and others like him are the intellectual opposition to advocates for longevity research. Here, Commonweal profiles Callahan: "The seventy-three-year-old Callahan was emphatic: It is a mistake, he told the council, to think that we have an obligation to pursue stem-cell work-or medical research generally, for that matter. Medical progress is certainly an important social good, but it must be weighed against competing social goods, such as education or decent housing. What's more, Callahan insisted, many of the diseases that stem-cell research might address, like cancer and heart disease, are illnesses of the old, and we must ask whether extending the human life span by a few more years through new treatments for these diseases is worth the cost. ... Callahan has sought to explore the folly of what he calls the 'gospel of medical progress'-namely, the idea that medicine brings the good news of liberation from death and dying." We should feel no shame in treading underfoot calls for the death of billions as we move towards the technologies that enable longer, healthier lives for all who so choose.

Repairing Muscle With Stem Cells (May 28 2007)
Work on urinary incontinence is demonstrating that reconditioning and repairing even more subtle damage in muscle function is within the present bounds of regenerative medicine. Via Medical News Today: "Previous studies in animal models [demonstrated] that injecting stem cells into the urethral muscles increases leak point pressure, leading to the restoration of the deficient muscles. The results of these studies formed the basis for the clinical trial. [Researchers] took biopsies of skeletal muscle tissue from eight female patients and isolated and expanded the stem cells from the tissue in culture. In an outpatient setting, the patients then received injections of the muscle-derived stem cells into the area surrounding the urethra. ... Five of the eight women who participated in the study reported improvement in bladder control and quality of life with no serious short- or long-term adverse effects one year after the initial treatment. ... A multi-center study in Canada and a study in the United States are currently underway and will allow researchers to determine the optimal dose of muscle stem cells."



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