Longevity Meme Newsletter, October 25 2010

October 25 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 Road to Commercial Tissue Engineering
- Considering Cryonics
- Discussion
- Latest Healthy Life Extension Headlines


Accelerating progress is underway in cell science: the ability to control cell actions, manage their growth and self-organization into tissue, and transform one cell type into another. Commercial production of tissue, and then whole organs to order is not far away:


"Researchers are well underway in the quest to control human cells: transforming cells from one type into another, for example, with an eye to creating low cost methods of producing cells for transplant on demand. Today's stem cell therapies and technology demonstrations of controlled cellular differentiation are the foundations of tomorrow's regenerative medicine, organ regrowth, and repair of age-worn tissues."


"Your liver is failing critically. A transplant would save your life, but there's a long waiting list and the odds are stacked against you. So instead, doctors extract some of your bone marrow, liver and muscle cells, go back to their laboratory and return in a few weeks with ... a freshly grown liver! Does this sound like material from a Hollywood sci-fi movie? Well not anymore. Australian researchers in Melbourne are now hard at work growing spare parts, proving their stuff in animal - and even human trials!"


"A large existing market primed to accept a new medical technology is a powerful thing: it can help to drive commercial application of that new technology far more rapidly than would otherwise happen. I've noted in the past that the hair restoration industry is a good example of this process in action. It's a large enough industry to support its own research community, and the concept of applying tissue engineering to hair regrowth is not a great leap for a customer already thinking about hair loss.

"An article [on] the work of Cytori Therapeutics makes the case for the industry of breast reconstruction and augmentation to be in a similar position to help advance tissue engineering technologies. ... breast augmentation is just one development (so to speak) in the company's more ambitious plan: to introduce stem cell medicine to the mass market ... It makes sense to apply Cytori's technology to enhance breasts instead of, say, repair urinary sphincters as a strategic way to move the patented technology out of rats and into people as soon as possible. Hearts, kidneys, and even sphincters have to work in order for us to survive. But we can live just fine without breast tissue, and, outside of feeding offspring, breasts don't have to do much. The fact is, the scientific and regulatory hurdles to getting Cytori's cells into clinical use will be easier to clear for breasts than for other tissue: Breasts simply aren't as necessary as other organs, so the bar for proving to regulators that the technology works will be lower."


We live in a mad world, in which a billion people have died of old age and disease whilst dismissing the available chance of eluding that fate:


"An ugly truth we have to face is that the technologies of rejuvenation, ways to repair the biochemical damage of aging in living bodies, will not arrive in time for everyone alive today. A billion, or two billion, or more people will die and decay to nothing simply because they were born too soon, or were on the cusp and didn't take good enough care of their health. For everyone who might paint a plausible picture of their lives on the wrong side of the line, cryonics is the best way forward - the only shot at a far longer and better life in a future age.

"As cryonics' determined subculture - clustered around a few companies such as Alcor - labors to make the theoretical into a reality, how close are we to actually making cryonics a real path to immortality? Well, in large measure, cryonics is real right here and now. Today, about a hundred people - including baseball legend Ted Williams who was frozen in 2003 - lie in liquid nitrogen baths awaiting resurrection and the cure for what ailed them. ... we're all left wondering why so few people step up to grasp this brass ring. Arranging your own cryopreservation requires time and effort - a lot of things can go wrong if you assume you don't need preparation and organization. But that isn't enough to explain why people don't go through with it.

"People's appetite for risk and change diminishes with age, it seems. The acceptance of personal oblivion seems to increase: it's the younger folk who are truly fiery on the topic of defeating death. One might argue on how much of that is physiological versus cultural - if you had the body and neurology of a 20 year old at 80, would you still have the same level of psychological inertia? It seems unlikely that we'll know the answer to that before there are 80 year olds with youthful physiques taking on the world."


The highlights and headlines from the past week follow below.

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We know that wealth correlates with greater life expectancy. Aging and late-life disease are the consequences of ongoing biological damage, and we might theorize that wealthier people on average have greater means and knowledge to reduce the rate at which that damage occurs - though I believe that knowledge and the will to use it are more important than means. No present day medical technology can do as much for a healthy person as exercise and calorie restriction, available to rich and poor alike. But all in all, we shouldn't be surprised to find statistically significant biological differences between the metabolisms of the wealthy and the poor, reflecting the differences in lifestyle and levels of biological damage: researchers "found evidence that biological ageing is slower among people with better socio-economic circumstances. ... It found that the wealthier people were, the higher their levels of DHEAS. The discovery raises the possibility that the hormone could be artificially produced and used to make people live longer. The scientists also found that those with higher levels of it tended to do greater amounts of exercise, lead a more active life with lots of pastimes, and have more friends and family. ... The research also found higher levels of a second hormone - growth factor I (IGF-I) - in those who are wealthier."

The p53 protein is a pivot point between aging and cancer: suppressing cancer at the cost of faster aging. p21 has a similar role, and is also a regulator of regeneration: p21-deficient mice are capable of regenerating injuries that normally don't heal in mammals. mTOR is a calorie restriction associated protein that when manipulated can extend life in mammals. These proteins influence many aspects of cell growth and other important metabolic processes, and are all tied together in the mechanisms of the cell: "The mechanism(s) by which p53 chooses between outcomes of senescence or quiescence has remained elusive. ... Recent studies [have] shown that [gene expression] of p21, a key p53 downstream target that is required for both senescence and quiescence, drives [cancer cells] into senescence ... Notably, rapamycin, a classical inhibitor of the mTOR pathway, can also suppress p21-mediated senescence suggesting the possibility that p53 might supress senescence by inhibiting mTOR signalling. Several key components of the mTOR pathway are, in fact, down-regulated by p53. ... Collectively, these analyses pinpoint p53-mediated inhibition of the mTOR pathway as a major effector in suppressing senescence, depending on whether p53 levels are above or below a critical threshold." This isn't all abstract low-level research: sophisticated manipulation of p53 can extend life in mice by 50%, and better understanding should mean better results.

Advanced glycation endproducts (AGEs) build up with age and cause all sorts of issues. As this paper notes, some of these problematic effects stem from RAGE, the cellular receptor for AGEs - which you might think of as one key upon the control keyboard for a cell. If that key is being constantly hammered by too many AGEs in the system, then that is a problem. "The formation of advanced glycation endproducts (AGEs) occurs in diverse settings such as diabetes, aging, renal failure, inflammation and hypoxia. The chief cellular receptor for AGEs, RAGE, transduces the effects of AGEs via signal transduction ... Data suggest that RAGE perpetuates the inflammatory signals initiated by AGEs via multiple mechanisms. AGE-RAGE interaction stimulates generation of reactive oxygen species and inflammation-mechanisms which enhance AGE formation. ... Taken together, these considerations place RAGE in the center of biochemical and molecular stresses that characterize the complications of diabetes and chronic disease. Stopping RAGE-dependent signaling may hold the key to interrupting cycles of cellular perturbation and tissue damage in these disorders." I'm still in favor of breaking down AGEs as the primary strategy: interfering in RAGE doesn't stop the build up of AGEs that causes it to be a problem in the first place.

Species with large differences in longevity between the genders - sometimes tenfold or more - might teach us something about the comparative importance of different mechanisms in aging. In bees, it appears to have much to do with resisting oxidative stress, and this looks to be the case for tarantulas as well: "Reactive oxygen species (ROS), i.e., the by-products of oxidative metabolism, have emerged as the main proximate cause of ageing. Because ROS are mainly produced by the mitochondria, their production is linked to metabolic rate, and this may explain the differences in longevity between large and small species. ... Mitochondrial superoxide production of hemolymph immune cells and antioxidant and oxidative damages plasma levels were measured in adult male and female [tarantulas] at different ages. We found that female spiders are producing less mitochondrial superoxide, are better protected against oxidative attack and are then suffering less oxidative damages than males at adulthood. ... once reaching sexual maturity, males have a life expectancy reduced to 1 to 2 years, while females can still live for 20 years, in spite of the fact that females continue to grow and moult. This study evidences an increased exposure of males to oxidative stress due to an increase in mitochondrial superoxide production and a decrease in hemolymph antioxidant defences. Such a phenomenon is likely to be part of the explanation for the sharp reduction of longevity accompanying male tarantula maturity."

An interesting study: "In human populations, variation in mate availability has been linked to various biological and social outcomes, but the possible effect of mate availability on health or survival has not been studied. Unbalanced sex ratios are a concern in many parts of the world, and their implications for the health and survival of the constituent individuals warrant careful investigation. We indexed mate availability with contextual sex ratios and investigated the hypothesis that the sex ratio at sexual maturity might be associated with long-term survival for men. Using two unique data sets of 7,683,462 and 4,183 men who were followed for more than 50 years, we found that men who reached their sexual maturity in an environment with higher sex ratios (i.e., higher proportions of reproductively ready men) appeared to suffer higher long-term mortality risks than those in an environment with lower sex ratios. Mate availability at sexual maturity may be linked via several biological and social mechanisms to long-term survival in men."

ON OVERPOPULATION (October 20 2010)
A defining characteristic of Malthusianism is that no matter how often it is proved wrong, you'll still find many who people fervently believe it. Overpopulation is a baseless fear, caused by a fundamental misunderstanding of the way in which people respond to potential scarcity. New resources are developed and old ones made more efficient - demand spurs progress in free societies. From a recent Reason Magazine article: "According to research published by the Royal Society, it looks as though the world will be able to feed 9 billion people by 2050, perhaps even allowing some farmland to revert to nature. Water is a problem, but economic and technological solutions show promise in ameliorating it. But more importantly, [overpopulationists] get the causality backwards. Poverty is the cause and high fertility is the symptom. Poverty traps and failed states which result in high maternal death rates, starvation, pollution, and deforestation are not created by population, but by bad policies. Working to spread economic freedom and political liberty is a lot harder than self-righteously blaming poor people for breeding too much. But it's the only real option."

From Accelerating Future: "Yesterday I had the pleasure of meeting John Furber, an anti-aging scientist known as the founder of Legendary Pharmaceuticals. The company's homepage has an excellent introduction to the biology of aging and senescence, and a giant chart with over a hundred nodes and links describing the process of aging. (I got to see a large poster version, which really had an impressive visual effect.) Furber's analysis of the mechanisms of aging are interesting because it strongly parallels Aubrey de Grey's but with a slightly different emphasis and other things to say. Furber has an article out in the hot-off-the-press Springer compilation The Future of Aging 'Repairing Extracellular Aging and Glycation'." Furber is one of the few researchers presently interested in developing a way to break down glucosepane, the most common advanced glycation end-product that builds up with age in human tissue, damaging biochemistry and causing some fraction of the process of degenerative aging.

An interview with the SENS Foundation founder: "I've always found that basic scientists who are interested in testing hypotheses think very differently from technologists who are interested in, you know, changing the world in some way. A large part of the difficulties I've had in getting my colleagues in gerontology to really understand what I'm saying is that they're all scientists and not really technologists. In this case what I'm saying is if we implement SENS properly, comprehensively, then it will actually postpone age-related ill health substantially. And we certainly don't have any data plus or minus on that because, of course, we haven't implemented it yet, right? ... 'theoreticians' or generalists are almost non-existent in biology. Unlike physics, where you've got whole departments of theoreticians trying to bring ideas together from disparate areas ... And to the extent it is known, it's given very little respect ... But the thing is, a small coterie of theoreticians in biology who do take care have a rather high hit rate. If you look at winners of the Nobel Prize in biology, you'll find a fair smattering of people who don't know how to work a pipette."

Politicians in the developed nations long ago set themselves upon the course to financial disaster. Matters are accelerating now, but all along it has been about the growth of entitlements, and especially forced transfers to wealth from the (largely poor) young to the (largely wealthy) old. As longevity increases, the system becomes ever more bankrupt - and the sooner it breaks down the better. Nothing more is needed to fix these problems than for the hand of government to be removed. "First the good news: We're living longer, healthier lives than ever before. ... Now for the bad news: At this rate, we can't afford to live so long. And by 'we,' I don't just mean you, me and our often insufficient long-term-care insurance policies. I mean 'we the people.' I mean the bureaucratic 'we.' ... For the first time in human history, people aged 65 and over are about to outnumber children under 5. In many countries, older people entitled to government-funded pensions, health services and long-term care will soon outnumber the work force whose taxes help finance those benefits. ... How are the most developed countries handling preparations for the boom in the elderly population - and for the budget-busting expenditures that are sure to follow? For a majority, not very well."

A longer article on branched chain amino acids (BCAA) and mouse longevity from Singularity Hub: "First and foremost, the work is in mice. Yes, mice are one of the most common test animals for longevity, and yes, the same BCAA cocktail also worked with yeast cells (another common test organism), but none of that means that humans are guaranteed to benefit. Second, the mice used were all males, and as we've seen with previous work in longevity, some techniques simply do not translate from one sex to another. Third, only 30 mice were used in the BCAA test group (30 in the control as well). That's simply not a very big sample. ... Finally, we should point out that while the Italian experiment showed a 12% increase in median lifespan, the range of lifespans didn't improve nearly as much. Maximum longevity for the BCAA mice was 1043 days compared to 979 days in the control group - a more modest 6.5% increase. If we look at the top 10% of mice in each group, the BCAA mice only improved 4.5% (981 compared to 938). In other words, while the amino acid treatments helped the mice live longer as a group, they didn't produce any super old mice."



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