Fight Aging! Newsletter, December 26th 2011

December 26th 2011

The Fight Aging! 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 Fight Aging!



- Politics, Perception, Money
- Diet Research: Far More of it Than is Necessary
- Living Long as an Ageless Individual
- Overestimating the Near Future
- Discussion
- Latest Headlines from Fight Aging!


We spend a fair amount of time asking why longevity research and development is so very poorly funded in comparison to the potential benefits it offers:

"Politics, perceptions, and money: these are the guiding trinity of research at the grand scale, the source of determinants for the work of thousands of researchers and the rate and direction of progress in broad fields of medical science - or so says the author of [a recent Scientific American] article on the state of longevity science: 'It has been clear for many years that the rate of aging is malleable in diverse species, and the discovery in 2009 that a drug called rapamycin can extend maximum life span in mice suggested that it's now technically feasible to develop anti-aging agents that really work as advertised. Unfortunately, I see no commercial interest in doing so.'

"The focus here is the mainstream of research, aimed at slowing aging by metabolic manipulation. This, as you all know by now, is the slow boat to nowhere in my view. The only practical way ahead that seems plausible to produce meaningful rejuvenation of the old in our lifetimes is some variant of SENS, the Strategies for Engineered Neligible Senescence: focus on repair and reversal of damage, not on slowing down the rate at which damage accrues. Repair is no harder, and arguably an easier path, and the end result will be far more effective in terms of years gained and suffering quashed. But SENS and other repair strategies yet to emerge into a coherent research program are the minority view in the field, still working to attain recognition and funding - bear that in mind when you read about the hurdles that groups with far more credit in the scientific community are struggling with. It's a long way from here to where we need to be, and there are two battles yet to win: firstly to persuade the research community to adopt the better strategic direction that SENS represents, and secondly to persuade some fraction of the world that reversing aging through biotechnology can and should be achieved within a matter of a few decades."


Some thoughts on science and the perpetual human fascination with what we put in our mouths:

"We live in a world of oral fixation, or whatever equivalent post-Freudian term you'd like to use. It's not too hard to drawn the lines that lead unbroken from the magic of early human societies, insofar as it touched on beliefs regarding the consumption of various things, and the magical thinking of modern societies illustrated by the popularity of useless potions and pills. On the one hand tricksters cloaked as shamans, and on the other hand tricksters cloaked as marketing professionals pretending to use the methods of science. For every hot field of medical science, there are frauds out there somewhere selling edible goods to the credulous, trying to claim some of the mantle.of legitimacy enjoyed by the scientific community while practicing what is in effect an anti-science of belief and deception.

"But back inside the real scientific community, we see the oral fixation at work in the amount and range of work on ingested substances. On diet, on tiny portions of diet, on the ingestion of specific substances beyond count, looking for results of significance. Funding for this sort of thing is evergreen, and I think that much of it is a grand waste. The path to longevity is not a freeway passing through the human stomach, but from the weight of research devoted to what we eat you might be forgiven for thinking otherwise. Would that these researchers were spending their time on something more useful, but the fixation of broader society on the mouth and what we put into it steers the strategic direction of research and research funding."


In the latest issue of the Rejuvenation Research journal, there's a short letter on gender and life expectancies in a future in which biotechnology has defeated aging:

"Life span [will be] limited even in biologically immortal individuals. Death can still occur from causes other than aging such as accident, extrinsic disease, murder, suicide, etc. Due to these factors, the statistical probability of extending life by eliminating aging has been estimated to range from as little as 700 years to a few thousand. Because women tend to take fewer risks than men, estimates for their survival are double those for men. Some authors speculate that because of future developments in medicine and technology, the risk for death can be even more significantly reduced, making it possible to extend human life for as much as 50,000 years. This estimate is obviously the extreme, but for argument's sake let's say it may be possible for cautious, biologically immortal individuals living conservative lifestyles to survive for 10,000 years or so before succumbing to a deadly contagion or catastrophic accident.

"Which initially suggests that a world of ageless individuals would be largely a world of women - though by the time agelessness is a going concern, I'd imagine that ad hoc gender transformation and selection will also be practical going concerns. Which is not to mention options beyond the traditional male or female duality, or elective alteration of mental traits such as appetite for risk, decoupling the mind from its biological influences. It's entertaining to take narrow slices of the future and ask how things would change is that one slice stood alone, but the future is a monolith - we'll get the potential for all of these outcomes of biotechnology at once, not one at a time.

"From where I stand, the technology needed to reduce risk for a standard issue human far enough to enable 50,000 years of life free from fatal occurrences would have to be some fairly advanced stuff - or at least that is so if the individuals in question intend to live free-range and interesting lives. Safety devices and autonomous watchdogs guided by strong artificial intelligences with millisecond reaction times and long planning horizons spring to mind. That sort of thing will be emerging within a hundred years at the present rate of development, but alongside will come the opportunity to stop being a standard issue human - a fragile package of tissue. The most robust way to reduce risk with the foreseeable high technology of the century ahead seems to be, to me at least, to transform the body rather than strive to protect it."


Predicting the future is subject to certain well-known biases:

"It is a truism that, in general, people who look ahead to the future both greatly overestimate predicted progress in the near term of twenty years or less and greatly underestimate predicted progress across longer timeframes. One might argue that this is due in part to most memorable predictions being made about industries and technologies in the early stages of an exponential curve - not much happens for many years as people experiment, persuade, bootstrap support and funding, and then a lot happens in a comparatively short period of time after someone hits the big time, gets it right, and the mainstream wakes up to the latest new new thing. But that's an oversimplification; there are many factors at work here, such as the many variants of hopeful but ultimately self-deluding optimism in the advocacy and technology development communities.

"So it is a useful exercise to temper our own predictions of what lies ahead with a look back at earlier well-thought-out and detailed predictions of past progress, to see where they fell down. Here's an example via New Cryonet, written in 1987, and making a set of predictions that, in many cases, have yet to come to pass despite being fairly reasonable - we are not as far along as we'd like to be."


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!



Friday, December 23, 2011
An example of the sort of screening work presently taking place, in China in this case: "Damaged heart tissue is not known for having much inherent capacity for repair. But now, scientists are closing in on signals that may be able to coax the heart into producing replacement cardiac muscle cells. Using a zebrafish model system, researchers have identified a family of molecules that can stimulate stem cells to develop into beating heart muscle cells. ... Despite advances in modern medicine, management of myocardial infarction and heart failure remains a major challenge. There is intense interest in developing agents that can influence stem cells to differentiate into cardiac cells as well as enhance the inherent regenerative capacities of the heart. Developing therapies that can stimulate heart muscle regeneration in areas of infarction would have enormous medical impact. ... The zebrafish is an excellent model organism to study heart growth and development because there are established genetic approaches that permit visualization of fluorescent beating hearts within transparent embryos. After screening nearly 4,000 compounds, the researchers discovered three structurally related molecules that could selectively enlarge the size of the embryonic heart. The compounds, cardionogen-1, -2, and -3, could promote or inhibit heart formation, depending on when they were administered during development. ... Cardionogen opposes Wnt signaling to induce cardiac muscle cell formation. Importantly, the interaction of cardionogen with Wnt seemed to be restricted to specific cell types. ... Evaluating the potential of cardionogen on human adult and embryonic stem cells is the next logical step. This may ultimately aid in design of therapeutic approaches to enhance repopulation of damaged heart muscle and restore function in diseased hearts."

Friday, December 23, 2011
A Rejuvenation Research paper: "As mammals age, the rate of neurogenesis in the brain declines with a concomitant reduction in cognitive ability. Recent data suggest that plasma-borne factors are responsible for inhibition of neurogenesis. When the circulatory systems of old and young mice are connected, the old mice experience increased neurogenesis and the young mice exhibit less neurogenesis, suggesting the importance of systemic circulating factors. Chemokine CCL11/eotaxin has been identified as a factor that increases with aging. Injections of CCL11 inhibit neurogenesis in young mice, an effect likely mediated by CCR3 receptors on neural stem cells. Identification of a specific factor that plays a causative role in stem cell dysfunction in aging is consistent with data showing that transforming growth factor-β (TGF-β) inhibits satellite cell-mediated repair. Together, these data suggest that the systemic milieu plays a critical role in the aging of adult stem cells. Because adult stem cells help maintain homeostasis by providing the possibility of replacing metabolically damaged differentiated cells, aging of the systemic milieu and stem cell niches may drive functional decline during aging. The identification of a specific systemic change suggests that aging is more amenable to therapeutic modulation than work on global metabolism-derived damage and cellular senescence implies."

Thursday, December 22, 2011
Here is an interesting application of guided tissue growth, that focuses on blood vessels. A wide range of work is under way on blood vessel engineering and control of growth, as the ability to incorporate blood vessels into tissue in specific ways is essential to realizing the most important goals of tissue engineering: "A team of engineers has created a bandage that in just one week not only encourages new blood vessel growth but helps guide that growth as well. ... The ability to pattern functional blood vessels at this scale in living tissue has not been demonstrated before. ... The team [calls] the bandage a 'microvascular stamp.' Unlike similar bandages developed to help spur blood vessel growth, the stamp contains living cells that encourage damaged tissue to grow according to the stamp's pattern. At nearly a centimeter across, the stamp is made of porous material that enables small molecules to sneak through in addition to the larger growth factors. The team tested it on a chicken embryo; when they removed it from the surface a week later, a network of new blood vessels appeared in the pattern of the stamp's channels. Future applications could include not only healing wounds, but also redirecting blood vessels to grow around blocked arteries, and even improving the delivery of cancer drugs by repairing blood vessels that feed cancerous cells."

Thursday, December 22, 2011
From the New Atlantis, a tour of some of the disturbing views of those who are opposed to enhanced longevity, and in favor of government force used to set limits to life: "Age-retardation technologies are the 'killer app' (so to speak) of enhancements - so deeply and self-evidently appealing that they would seem to sell the whole project of enhancement on their own. Nonetheless, there are those who oppose them. For example, Leon Kass, the former chairman of the President's Council on Bioethics (PCBE) under President Bush, has asserted, 'the finitude of human life is a blessing for every individual, whether he knows it or not.' And Daniel Callahan, co-founder of the Hastings Center, has declared, 'There is no known social good coming from the conquest of death.' Callahan added, 'The worst possible way to resolve [the question of life extension] is to leave it up to individual choice.' When asked if the government has a right to tell its citizens that they have to die, Johns Hopkins University political scientist Francis Fukuyama answered, 'Absolutely.' ... In addition to these concerns, Schaub suggests that 'a nation of ageless individuals could well produce a sclerotic society, petrified in its ways and views.' Daniel Callahan makes a similar argument in a debate with life-extension advocate Gregory Stock, in which he claims, 'I doubt that if you give most people longer lives, even in better health, they are going to find new opportunities and make new initiatives.' Stock goes so far as to help his interlocutor with the hoary example of brain-dead old professors blocking the progress of vibrant young researchers by holding onto tenure. But that seems more of a problem for medieval institutional holdovers like universities than for modern social institutions like corporations. ... In fact, the available evidence cuts against concerns about 'a hardening of the vital social pathways.' Social and technological innovation has been most rapid in those societies with the highest average life expectancies. Yale economist William D. Nordhaus estimates that increases in longevity in the West account for 40 percent of the growth in gross national product for the period 1975-1995. Why? Not only do people work longer, but they work smarter - long lives allow for the accumulation of human capital. ... We do not know what immortality would be like. But should that happy choice become available, we can still decide whether or not we want to enjoy it. Besides, even if the ultimate goal of this technological quest is immortality, what will be immediately available is only longevity. The experience of longer lives will give the human race an opportunity to see how it works out. If immortality is a problem, it is a correctable one. Death always remains an option. Let us turn on its head the notorious argument by Leon Kass that our initial repugnance to biotechnological advances should make us wary of them. Put the other way around, the near-universal human yearning for longer, healthier lives should serve as a preliminary warrant for pursuing age-retardation as a moral good."

Wednesday, December 21, 2011
A study here shows that calorie restriction reduces levels of mitochondrial damage that accumulates with age - that damage being thought of as a contributing cause of aging - but in different levels in different tissues and different species: "The hypothesis that life-span extension by caloric restriction (CR) is contingent upon the attenuation of macromolecular oxidative damage was tested in two different strains of mice: the C57BL/6, whose life span is extended by CR, and the DBA/2, in which CR has relatively minor or no impact on longevity. Mice were fed ad libitum (AL) or restricted to 40% lesser food, starting at 4 months of age. Protein damage was measured as protein-linked adducts of 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) in skeletal muscle mitochondria at 6 and 23 months of age. Protein-HNE and -MDA content increased with age in C57BL/6 mice and CR significantly attenuated these augmentations. ... DBA/2 mice exhibited little effect of age or CR on protein HNE/MDA content in skeletal muscle mitochondria. In contrast, protein-HNE levels in liver mitochondria showed a significant increase with age in AL-fed mice of both strains, and CR caused significant attenuation of this damage. Overall, results indicated that the age-related increase in protein oxidative damage and its abatement by CR are genotype- and tissue-specific, and not a universal phenomenon."

Wednesday, December 21, 2011
An open access paper that suggests that producing therapies for the characteristic loss of muscle mass and strength with age - known as sarcopenia - may be more challenging than we'd like it to be: "Several age-related changes occur in skeletal muscle including a decrease in myofiber size and number and a diminished ability of satellite cells to activate and proliferate upon injury leading to impaired muscle remodeling. Although the molecular mechanisms underlying sarcopenia are unknown, it is tempting to hypothesize that interplay between biological and environmental factors cooperate in a positive feedback cycle contributing to the progression of sarcopenia. Indeed many essential biological mechanisms such as apoptosis and autophagy and critical signaling pathways involved in skeletal muscle homeostasis are altered during aging and have been linked to loss of muscle mass. Moreover, the environmental effects of the sedentary lifestyle of older people further promote and contribute the loss of muscle mass. There are currently no widely accepted therapeutic strategies to halt or reverse the progression of sarcopenia. Caloric restriction has been shown to be beneficial as a sarcopenia and aging antagonist. Such results have made the search for caloric restriction mimetics (CRM) a priority. However given the mechanisms of action, some of the currently investigated CRMs may not combat sarcopenia. Thus, sarcopenia may represent a unique phenotypic feature of aging that requires specific and individually tailored therapeutic strategies."

Tuesday, December 20, 2011
Systems biology is the natural evolution of the present mainstream research into metabolism, epigenetics, cellular mechanisms, and aging: tie it all together into one holistic view of how the body works and then fails with age. Here is an example of that sort of viewpoint, and how it reinforces conclusions such as the need to address cellular senescence: "The role of cellular senescence (CS) in age-related diseases (ARDs) is a quickly emerging topic in aging research. Our comprehensive data mining revealed over 250 genes tightly associated with CS. Using systems biology tools, we found that CS is closely interconnected with aging, longevity and ARDs, either by sharing common genes and regulators or by protein-protein interactions and eventually by common signaling pathways. The most enriched pathways across CS, ARDs and aging-associated conditions (oxidative stress and chronic inflammation) are growth-promoting pathways and the pathways responsible for cell-extracellular matrix interactions and stress response. Of note, the patterns of evolutionary conservation of CS and cancer genes showed a high degree of similarity, suggesting the co-evolution of these two phenomena. Moreover, cancer genes and microRNAs seem to stand at the crossroad between CS and ARDs. Our analysis also provides the basis for new predictions: the genes common to both cancer and other ARD(s) are highly likely candidates to be involved in CS and vice versa. Altogether, this study shows that there are multiple links between CS, aging, longevity and ARDs, suggesting a common molecular basis for all these conditions. Modulating CS may represent a potential pro-longevity and anti-ARDs therapeutic strategy."

Tuesday, December 20, 2011
An open access review paper: "Cell therapy has been established as an important field of research with considerable progress in the last years. At the same time, the progressive aging of the population has highlighted the importance of discovering therapeutic alternatives for diseases of high incidence and disability, such as stroke. Menstrual blood is a recently discovered source of stem cells with potential relevance for the treatment of stroke. Migration to the infarct site, modulation of the inflammatory reaction, secretion of neurotrophic factors, and possible differentiation warrant these cells as therapeutic tools. We here propose the use of autologous menstrual blood cells in the restorative treatment of the subacute phase of stroke. ... Menstrual blood cell injections are proposed [to] provide functional improvement and, therefore, decrease disability of the affected patients. Migration to the site of injury, immunomodulation, and secretion of neurotrophic factors are their main footholds as therapeutic agents. When compared to bone marrow-derived cells, menstrual blood cells present more immature phenotype and behavior, albeit maintaining the characteristic adult stem cell safety. Experimental studies have demonstrated benefits of menstrual blood cell administration, with tissue repair and functional improvement, not only in the central nervous system, but also in the heart and ischemic limbs."

Monday, December 19, 2011
A look at the role of chronic inflammation in Alzheimer's disease: "Even today, Alzheimer's is still a disease that is definitively diagnosed only after death and autopsy, when it is easy to recognize the disease's cardinal features: a shrunken brain with amyloid plaques dotted among neurons laden with neurofibrillary tangles, and often with inclusions similar to those found in the brains of patients who have died of Parkinson's. These irrefutable histological markers of Alzheimer's led to the logical conclusion by most researchers that plaques are the cause of the problem. Many pharmaceutical companies have taken vigorous aim at amyloid with no clear evidence so far that ridding the brain of plaques in Alzheimer's disease results in cognitive improvement. Lacking a smoking gun that definitively singles out the plaques as the causative agent, amyloid is the scientific equivalent of a culprit assumed guilty until proven innocent. ... Mounting evidence shows that inflammation plays a critical role in causing Alzheimer's disease. Over the last few decades we have gone from a situation where inflammation was generally believed to have no role in the disease to the current picture where chronic activation of IL-1 inflammation has been shown to account for many of the hallmarks of the disease. This review is a personal account of the quest to prove that inflammation plays a critical role in causing Alzheimer's disease."

Monday, December 19, 2011
One part of longevity research is to screen as many as possible existing drugs on cells and lower animals to see what effect they have; it's a first step that may then lead on to finding epigenetic changes to replicate the effect, and then uncover the underlying mechanisms which may point towards novel longevity mutations. This is a long road - consider that researchers still don't fully understand calorie restriction, for example, never mind more recently discovered effects. Here is an open access paper that illustrates how this research process works. Note that the choice of compounds to check is steered by regulation rather than by scientific knowledge - not a good situation: "Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications."



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