Longevity Meme Newsletter, April 26 2010

April 26 2010

The Longevity Meme Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to the Longevity Meme.



- The Revealed Slow Aging Hypothesis
- The State of Innate Immune Therapies for Cancer
- Quantifying the Harm Done by Cytomegalovirus
- Recent Longevity Study Results
- Discussion
- Latest Healthy Life Extension Headlines


An interesting idea, albeit hard to prove one way or another at this stage of our progress in biotechnology:


"To what degree might we attribute the accelerating rise in human life span in recent centuries to an increased survival rate for people who bear gene variants that (a) harm the prospects for survival to adulthood in low-technology settings, but (b) lead to a longer life expectancy for those who do survive?"


The transplant of leukocyte or granulocyte immune cells has shown great promise in destroying even advanced cancer, but little work is being done to bring this from the laboratory to the clinic:


"You might recall that people were enthused a few years back over the work of researcher Zheng Cui, who showed that (a) one breed of lab mice shug off cancer because their immune cells are different in ways that enable them to kill cancer dead, (b) transplanting those immune cells into more vulnerable mice also kills cancer dead, and (c) this same state of affairs exists in humans. Somewhere, someone has an immune system that can kill your cancer. If you could find them and undergo a transplant of leukocyte or granulocyte immune cells, the evidence to date suggests that this would be a very effective therapy. As put by the folk at Livly, a non-profit startup focused on bringing this form of therapy into the clinic: Results like this suggest to us that innate immunotherapy is the only approach that has shown the promise to permanently cure advanced cancer. Ironically, it is also one of the most neglected areas in contemporary research."


Nearly all of us have cytomegalovirus (CMV) lurking in our bodies by the time we are old, and it is one of the reasons why our immune systems decline dramatically with advancing age:


"Most people are exposed to this mild persistent herpesvirus over the course of their life; it causes few obvious symptoms, but over time more and more of your immune system resources become uselessly specialized to fight it. An immune cell dedicated to remembering the signature of CMV is unavailable for other uses - and eventually you run out of cells to protect you from new threats, destroy cancers, and clear out senescent cells.

"A CMV fixation should be thought of as yet another form of malfunction or misconfiguration of the immune system, to be put in the same broad category as autoimmune diseases. Some of the research efforts directed towards repairing autoimmune disease may in the future also be turned towards repairing a CMV-specialized immune system. For example, researchers have successfully rebooted the immune system in human patients in recent years: completely destroying and then recreating it in order to remove all immune cells with errant programming. Another possibility is the use of targeted cell killing technologies that can pick out and destroy CMV-specialized immune cells based on their surface markers."


Some examples from recent studies of genetic components of human longevity:


"More genetic and other studies of long-lived people are taking place these days, which means a faster flow of results than has been the case in past years. Part of that can no doubt be attributed to an increased interest in manipulating the aging process in the scientific community, as well as the continually falling cost of the tools needed to run such studies. ... There are an unknown but almost certainly large number of small contributory factors making up the genetic component of human longevity, and they are being uncovered at an accelerating pace. What does this all mean for you and I? Probably very little. We will not gain greatly extended longevity through tinkering with our haplotypes - by the time genetic tweaks are happening in the clinic, we will be old. Changes to metabolism that make a year or two's difference in life span across an entire lifetime will be next to worthless to someone already in late life, and already seriously damaged by aging. We should welcome the advances in practice and understanding of human biology and aging, because all such information will at some point be useful, but we must also recognize that genetic alterations to slow aging are not the path to extending our own lives. We must instead focus on the repair of age-related changes, such as that proposed by the Strategies for Engineered Negligible Senescence."



The highlights and headlines from the past week follow below.

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More evidence for the benefits of exercise: "Researchers from the University of Washington conducted a six-month clinical trial with 33 participants, 17 of whom were women. All showed early signs of Alzheimer's disease and were between the ages of 55 and 85. The experiment participants underwent a six-month intensive aerobic training program, spending 45 minutes to an hour four times each week on a stationary bicycle or treadmill. At the end of the six months, the participants saw improvement in mental agility, while the control group showed no improvement. Researchers are planning further studies to conduct larger and longer duration trials, following volunteers for years instead of months, for more conclusive data as to whether exercise can prevent full-blown cases of Alzheimer's. ... Other similar studies have been conducted, where researchers have measured the health benefits of resistance training for women between the ages of 65 and 75 who are most at risk for developing Alzheimer's. In one study, after one year of training, women who had completed the training showed better scores on mental acuity and conflict resolution tests than those who didn't."

Possibly an example of overthinking the issue at the JET, but the section on Finot illustrates that our era does not enjoy a monopoly on rational thinking about extending the healthy human life span: "The beginning of the modern period in the pursuit of radical human enhancement and longevity can be traced to fin-de-siecle/early twentieth-century scientific and technological optimism and therapeutic activism. The works of several authors of the period - Fedorov, Stephens, Bogdanov, Nietzsche and Finot - reveal conflicting ideological and social pathways toward the goals of human enhancement and life extension. Each author represents a particular existing social order, and his vision of human advancement may be seen as a continuation and extension of that order. Therefore, the pursuit of life extension may be considered a fundamentally conservative (or conservationist) enterprise. ... First, these adaptations may question the claims of a particular ideology for supremacy in the promotion of life-extension and life-enhancement. The claims that atheism, capitalism or hedonism are more conducive to the pursuit of longevity, can be countered by historical examples where religion, socialism or asceticism were the foundations. No ideological system seems to have a monopoly, however strongly it asserts that it constitutes the rock-solid ground for this pursuit. It may be that, rather than providing such a foundation, political ideologies enlist the hope for life extension to increase their appeal."

From the Telegraph, news of continuing incremental progress in understanding the mechanisms of regeneration in lower animals: "research into how Planarian worms can regrow body parts - including a whole head and brain - could one day make it possible to regenerate old or damaged human organs and tissues ... We want to be able to understand how adult stem cells can work collectively in any animal to form and replace damaged or missing organs and tissues. ... Any fundamental advances in understanding from other animals can become relevant to humans surprisingly quickly. If we know what is happening when tissues are regenerated under normal circumstances, we can begin to formulate how to replace damaged and diseased organs, tissues and cells in an organised and safe way following an injury caused by trauma or disease. This would be desirable for treating Alzheimer's disease, for example. With this knowledge we can also assess the consequences of what happens when stem cells go wrong during the normal processes of renewal - for example in the blood cell system where rogue stem cells can result in Leukaemia."

Life is getting better: "Human society has changed much over the last centuries and this process of 'modernization' has profoundly affected the lives of individuals; currently we live quite different lives from those forefathers lived only five generations ago. There is difference of opinion as to whether we live better now than before and consequently there is also disagreement as to whether we should continue modernizing or rather try to slow the process down. Quality-of-life in a society can be measured by how long and happy its inhabitants live. Using these indicators I assess whether societal modernization has made life better or worse. Firstly I examine findings of present day survey research. I start with a cross-sectional analysis of 143 nations in the years 2000-2008 and find that people live longer and happier in today's most modern societies. Secondly I examine trends in modern nations over the last decade and find that happiness and longevity have increased in most cases. Thirdly I consider the long-term and review findings from historical anthropology, which show that we lived better in the early hunter-gatherer society than in the later agrarian society. Together these data suggest that societal evolution has worked out differently for the quality of human life, first negatively, in the change from a hunter-gatherer existence to agriculture, and next positively, in the more recent transformation from an agrarian to an industrial society. We live now longer and happier than ever before."

Spanish scientists "have generated artificial human skin by [tissue] engineering based on agarose-fibrin biomaterial. The artificial skin was grafted onto mice, and optimal development, maturation and functionality results were obtained. This pioneering finding will allow the clinical use of human skin and its use in many laboratory tests on biological tissues - which, additionally, would avoid the use of laboratory animals. Further, this finding could be useful in developing new treatment approaches for dermatological pathologies. ... The skin created in the laboratory showed adequate biocompatibility rates with the recipient and no rejection, dehiscence or infection was registered. ... The experiment [is] the first to create artificial human skin with a dermis made of fibrin-agarose biomaterial. To this date, artificial skin substitutes were elaborated with other biomaterials as collagen, fibrin, polyglycolic acid, chitosan, etc. These biomaterials [added] resistance, firmness and elasticity to the skin. ... Definitively, we have created a more stable skin with similar functionality to normal human skin."

A number of studies in recent years have suggested that calorie intake is not the only thing that can alter metabolism to change longevity in lower animals: "Specific odors that represent food or indicate danger are capable of altering an animal's lifespan and physiological profile by activating a small number of highly specialized sensory neurons ... Recent research in model organisms and in humans has shown that sensory experiences can impact a wide range of health-related characteristics including athletic performance, type II diabetes, and aging. Nematode worms and fruit flies that were robbed of their ability to smell or taste, for example, lived substantially longer. However, the specific odors and sensory receptors that control this effect on aging were unknown. Using molecular genetics in combination with behavioral and environmental manipulations, [researchers have identified] carbon dioxide (CO2) as the first well-defined odorant capable of altering physiology and affecting aging. Flies incapable of smelling CO2 live longer than flies with normal olfactory capabilities. They are also resistant to stress and have increased body fat. To many insects, including fruit flies, CO2 represents an ecologically important odor cue that indicates the presence of food (e.g. rotting fruit or animal blood) or neighbors in distress (it has been implicated as a stress pheromone). Indeed, this group of researchers previously showed that merely sensing one's normal food source is capable of reversing the health and longevity benefits that are associated with a low calorie diet. They now establish that CO2 is responsible for this effect."

The Humanity+ Summit will be held in June at Harvard: "The H+ Summit is part of a larger cultural conversation about what it means to be human and, ultimately, more than human. This issue lies at the heart of the transhumanism movement ... The H+ Summit is a two day event that explores how humanity will be radically changed by technology in the near future. Visionary speakers will explore the potential of technology to modify your body, mind, life, and world. What will it mean to be a human in this next phase of technological development? How can we prepare now for coming changes? We foresee the feasibility of redesigning the human condition and overcoming such constraints as the inevitability of aging, limitations on human and artificial intellects, unchosen psychology, lack of resources, and our confinement to the planet earth. The possibilities are broad and exciting. The H+ Summit will provide a venue to discuss these future scenarios and to hear exciting presentations by the leaders of the ongoing H+ (r)evolution." Amongst the confirmed speakers is biomedical gerontologist and engineered longevity advocate Aubrey de Grey, whose presentations are always well worth attending.

Cancer would be far less threatening a condition if metastasis could be reliably blocked: "Like microscopic inchworms, cancer cells slink away from tumors to travel and settle elsewhere in the body. Now, [researchers report] that new anti-cancer agents break down the looping gait these cells use to migrate, stopping them in their tracks. Mice implanted with cancer cells and treated with the small molecule macroketone lived a full life without any cancer spread, compared with control animals, which all died of metastasis. When macroketone was given a week after cancer cells were introduced, it still blocked greater than 80 percent of cancer metastasis in mice. ... macroketone targets an actin cytoskeletal protein known as fascin that is critical to cell movement. In order for a cancer cell to leave a primary tumor, fascin bundles actin filaments together like a thick finger. The front edge of this finger creeps forward and pulls along the rear of the cell. Cells crawl away in the same way that an inchworm moves. Macroketone latches on to individual fascin, preventing the actin fibers from adhering to each other and forming the pushing leading edge."

An interesting paper: "The idea that bodies wear out with age is so ancient, so pervasive, and so deeply rooted that it affects our thought in unconscious ways. Undeniably, many aspects of aging, e.g., oxidative damage, somatic mutations, and protein cross-linkage are characterized by increased entropy in biomolecules. However, it has been a scientific consensus for more than a century that there is no physical necessity for such damage. Living systems are defined by their capacity to gather order from their environment, concentrate it, and shed entropy with their waste. Organisms in their growth phase become stronger and more robust; no physical law prohibits this progress from continuing indefinitely. Indeed, some animals and many plants are known to grow indefinitely larger and more fertile through their lives. The same conclusion is underscored by experimental findings that various insults and challenges that directly damage the body or increase the rate of wear and tear have the paradoxical effect of extending life span. Hyperactive mice live longer than controls, and worms with their antioxidant systems impaired live longer than wild type. A fundamental understanding of aging must proceed not from physics but from an evolutionary perspective: The body is being permitted to decay because systems of repair and regeneration that are perfectly adequate to build and rebuild a body of ever-increasing resilience are being held back. Regardless of the reason for this retreat, it should be more fruitful to focus on signaling to effect the ongoing activity of systems of repair and regeneration than to attempt repair of the manifold damage left in the wake of their failure."

Spurring regeneration by use of signalling molecules is a promising field of medical development. Here is an example from the Technology Review: "scientists have identified a pair of peptides that can stimulate new cell growth and improve heart function in rodents induced to have heart attacks. [Researchers are] now testing one of the peptides, periostin, in pigs induced to have heart attacks. Because these animals have hearts similar in size to humans, they provide a good model for testing new therapies prior to human clinical trials. Preliminary results show that injecting the peptide into the pericardium, the lining around the heart, seems to help. ... [This] approach is, to some degree, in competition with stem-cell therapy, which is already being tested in humans. Scientists are working on different ways of harvesting and delivering stem cells to patients with heart disease, and clinical trials have so far yielded mixed results. Transplanted cells appear to have difficulty surviving and integrating into their new environment. In fact, some scientists suggests that benefit of cell transplants comes from the cells ability to stimulate innate growth. Triggering this process with peptides [may] be a simpler method of treatment of certain conditions such as cardiomyopathy [an enlarged heart] where the problem is lack of viable, contractile heart muscle cells."



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