Fight Aging! Newsletter, November 28th 2011

November 28th 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!



- The Long View
- Following Up on a Tissue Engineered Trachea Transplant
- Discussion
- Latest Headlines from Fight Aging!


A few thoughts on the present and the future:

"Long after the time in which anyone can easily recall who was US president in 2011, or what party was in power, or which wars of declining empire are fought, and then long after anyone even cares about that ancient history, and later, long after the whole download slope of the history of the US is but a footnote of interest to scholars of the transition from second to third millennium, and later still, long after anyone can even find out with any great reliability who was US president in 2011, the first half of the 20th century will be recalled as the dawn of the era in which aging was conquered.

"Progress in science and technology is really the only thing that matters in the long term. In that area of human endeavor, the truly transformative advances stand out like beacons across millennia of time - even long after the details of that period are hard to reconstruct, archaeologists can show clearly both when and how the use and understanding of technology changed. So we see the impact of agriculture and we know when it began, for example: it looms large in our considerations of deep human history at the present time, because it utterly transformed the course of our species. Similarly for iron working, and other important advances.

"The advent of ways to reverse the effects of aging, largely through biotechnologies in the early stages of development that will repair the low-level biochemical damage that causes aging, will transform the shape and course of human society no less than the great advances of prehistory and early history - but undoubtedly much faster, as we're far better at talking to one another and coordinating our efforts in these years.

"So in the final analysis, how much of what we do in our day to day lives actually matters? That's a meaning of life sort of a question, so everyone gets to write their own answer into the box and it's still right, but it's intended to provoke thought. Do you care about end results, or do you care about the journey? Billions of lives in the future hang in the balance of a few dollars or a convincing argument for the development of rejuvenation biotechnology: it's early enough still that we're talking butterfly wings and hurricanes when it comes to how our efforts today will affect the next four decades of progress in ways to slow and reverse aging. I suppose, for someone like myself who isn't in it so much for the journey, it's the case that you can choose to live a life in which you made a difference, or you can choose to live a life in which it doesn't much matter whether you ever existed.

"The future can be made a golden place within our lifetimes, and billions of people who are presently destinated to suffer and age to death could instead by saved through biotechnology to live full, healthy, and vigorous lives thousands of years long. That all depends on how well and rapidly the present research community works on the first generation of rejuvenation therapies, which in turn depends on acts of fundraising and persuasion carried out by otherwise ordinary folk like you and I. There's an avalanche to be started here, a few pebbles that will bring the whole slope rushing down with it, profoundly transform humanity in the process by banishing aging and the decrepitude, disease, and death it brings."


Engineering and transplant of simpler solid tissue structures is doing very well:

"You may recall that an Italian group has been engineering and transplanting comparatively simple organ structures - such as tracheas - in recent years. The researchers have used a range of techniques to build these organs from the patient's own cells, such as decellularization and nanoscale polymer scaffolds. The former requires a donor organ to be stripped of cells in order to provide a scaffold formed of its extracellular matrix, while the latter results in a completely synthetic organ. In both cases, the raw materials that form that scaffold are populated with the patient's own cells, leading to a transplant without the risk of immune rejection. This is all very promising groundwork for later and more extensive tissue engineering of replacement parts to order. The first synthetic trachea transplant occurred earlier this year, and an update is doing the rounds."


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, November 25, 2011
There have been a number of research results in the past year or two that suggest the barriers posed by age to the production of patient-specific cells suitable for stem cell therapies are lower than first thought. Several research groups have obtained useful cells from old patients, showing that age-related damage to patient cells is no barrier to reprogramming them - indeed, the reprogramming appears to repair many types of damage. Here is another such result: "Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs) acquire features of human embryonic stem cells (hESCs) and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. ... Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the [potential of reprogrammed cells to spawn cancer] due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. ... Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. ... all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence of genomic alterations."

Friday, November 25, 2011
We are our brains, and so there isn't much room for outright replacement with new tissue as a strategy for regeneration anywhere inside the skull. Thus it is very important that researchers develop ways to repair the brain in situ. Fortunately, it looks as though this goal will be achievable sooner rather than later, with comparatively early stage stem cell therapies: "Neuron transplants have repaired brain circuitry and substantially normalized function in mice with a brain disorder, an advance indicating that key areas of the mammalian brain are more reparable than was widely believed. ... [Researchers] transplanted normally functioning embryonic neurons at a carefully selected stage of their development into the hypothalamus of mice unable to respond to leptin, a hormone that regulates metabolism and controls body weight. These mutant mice usually become morbidly obese, but the neuron transplants repaired defective brain circuits, enabling them to respond to leptin and thus experience substantially less weight gain. Repair at the cellular-level of the hypothalamus - a critical and complex region of the brain that regulates phenomena such as hunger, metabolism, body temperature, and basic behaviors such as sex and aggression - indicates the possibility of new therapeutic approaches to even higher level conditions such as spinal cord injury, autism, epilepsy, ALS (Lou Gehrig's disease), Parkinson's disease, and Huntington's disease. ... There are only two areas of the brain that are known to normally undergo ongoing large-scale neuronal replacement during adulthood on a cellular level - so-called 'neurogenesis,' or the birth of new neurons - the olfactory bulb and the subregion of the hippocampus called the dentate gyrus, with emerging evidence of lower level ongoing neurogenesis in the hypothalamus. The neurons that are added during adulthood in both regions are generally smallish and are thought to act a bit like volume controls over specific signaling. Here we've rewired a high-level system of brain circuitry that does not naturally experience neurogenesis, and this restored substantially normal function."

Thursday, November 24, 2011
Researchers are foraging for longevity-related genes that have nothing to do with the known processes of life extension through calorie restriction: "We believe that for the first time, we have a biochemical route to youth and aging that has nothing to do with diet. ... The chemical variation, known as acetylation because it adds an acetyl group to an existing molecule, is a kind of 'decoration' that goes on and off a protein - in this case, the protein Sip2 - much like an ornament can be put on and taken off a Christmas tree ... Acetylation can profoundly change protein function in order to help an organism or system adapt quickly to its environment. Until now, acetylation had not been directly implicated in the aging pathway, so this is an all-new role and potential target for prevention or treatment strategies, the researchers say. The team showed that acetylation of the protein Sip2 affected longevity defined in terms of how many times a yeast cell can divide, or 'replicative life span.' The normal replicative lifespan in natural yeast is 25. In the yeast genetically modified by researchers to restore the chemical modification, life span extended to 38, an increase of about 50 percent. The researchers were able to manipulate the yeast life span by mutating certain chemical residues to mimic the acetylated and deacetylated forms of the protein Sip2. They worked with live yeast in a dish, measuring and comparing the life spans of natural and genetically altered types. ... When we give back this protein acetylation, we rescued the life span shortening in old cells. Our next task is to prove that this phenomenon also happens in mammalian cells."

Thursday, November 24, 2011
A PDF document that I think you'll find interesting: "Reports on the latest research of what makes us unhealthy, or what could make us live longer, are common from magazines, newspapers and websites. Often, the messages get shortened so that it sounds like one risk factor dominates. The reality is that the way in which many relevant risk factors work together is still not yet fully understood, and there is an element of chance affecting the longevity prospects of each of us. ... the overarching context is consistent improvement in longevity worldwide. Life expectancy has only ever declined in a few countries subject to specific and significant negative mortality risk. While we need to examine the trees of individual risk factors, there is much to be said for pausing to look at the woods of the consistent achievement in longevity progress. Longevity Bulletin aims to provide a regular guide to the prospects for long lives. It presents and explains actuarial perspectives on population longevity and looks outside the profession for statistics, research and the latest thinking on related subjects. It is not intended as a comprehensive guide to everything new in longevity research but rather as a helpful companion for those interested in a most intriguing subject."

Wednesday, November 23, 2011
A reminder that progress in the production of nanoscale scaffolds and surfaces is just as important as progress in biology in the stem cell field: "It's easy to give a stem cell a goal in life, apparently. Simply placing a cell in contact with a surface can provide sufficient information (a cue) to dictate how the cell will develop, and incredibly, even simple length-scale changes are enough to affect the outcome of the cell development. Far-fetched as this may sound, if you think about the nature of stem cells for a moment, it becomes less surprising that they are so responsive to their environment: how else to explain the extraordinary variety of cell types that derive from a uniform base material? As stem cells continue to be the focus of much research into the concepts of regenerative medicine and tissue engineering, a corollary challenge for materials science is the design and build for artificial substrates that can mimic biological environments and thereby control the growth and specialization of the cells. For one thing, the subtleties make it easy to grow off in the wrong direction. Growing muscle tissue will need a different set of conditions from, say, a new liver, but the differences in the environment might turn out to be very slight. A small change in the period of a pattern on the substrate might result in completely the wrong kind of tissue. A challenge of a more mechanical nature is the actual fabrication of the substrates. Most cell-growth environments have cues that act over a number of different length scales, with multiple patterns and features of various sizes interacting to produce the end result. Current micro- and nanofabrication techniques don't mimic this complexity too well, or rather, don't mimic it too well without complex multi-step procedures, expensive instrumentation, and expertise on fabrication that is not readily available to medical researchers."

Wednesday, November 23, 2011
The Genomics X Prize has been a while in the building, and has a focus on the genetics of human longevity. It has been in the news of late: "The contest to sequence 100 complete human genomes of people who are over 100 years old in one month for $1,000 or less per genome has started its recruitment process and has pulled in new several new partners to help it develop its sampling, protocols, informatics, and other scientific needs. ... The Archon Genomics X PRIZE [is] an incentivized prize competition that will award $10 million to the first team to rapidly, accurately and economically sequence 100 whole human genomes to a level of accuracy never before achieved. The 100 human genomes to be sequenced in this competition will be donated by 100 centenarians (ages 100 or older) from all over the world, known as the Medco 100 Over 100. Sequencing the genomes of the Medco 100 Over 100 presents an unprecedented opportunity to identify those 'rare genes' that protect against diseases, while giving researchers valuable clues to health and longevity. These centenarians' genes are providing us with a window to the past that will significantly impact the future of healthcare. The result will be the world's first 'medical grade' genome, a critically-needed clinical standard that will transform genomic research into usable medical information to improve patient diagnosis and treatment. This global competition will inspire breakthrough genome sequencing innovations and technologies that will usher in a new era of personalized medicine."

Tuesday, November 22, 2011
One of the benefits of pregnancy is increased regenerative ability in the mother, a fact observed in a number of studies. The underlying mechanisms are illustrated in recent research, and is one of a number of related effects that might inform future research directions in regenerative medicine: "Scientists are devoting countless research hours to treatments based on embryonic stem cells, differentiating these blank-slate cells from embryos into brain cells, light-sensing retinal cells, blood cells, and more to replace damaged or destroyed tissues in the body. Now, a new study in mice shows such that nature has arrived at just such a solution, too: When a pregnant mouse has a heart attack, her fetus donates some of its stem cells to help rebuild the damaged heart tissue. ... The researchers started with two lines of mice: normal mice and mice genetically engineered to express green fluorescent protein (GFP), which glows a distinctive green when exposed to blue light, in their cells. They mated normal female mice with GFP-producing male mice. This meant that half the resulting fetuses had the GFP gene, too, making their cells glow, too. Twelve days later - a little less than two-thirds of the way through a normal mouse pregnancy - the researchers gave half the pregnant mice heart attacks. When the scientists examined the female mice's heart tissue two weeks after the heart attacks, they found lots of glowing green tissue - cells that came from the fetus - in the mom's heart. Mice who had heart attacks had eight times as many cells from the fetus in their hearts as mice who hadn't had a heart attack did, meaning the high volume of fetal cells was a response to the heart attack. ... Doctors have observed that women who experience weakness of the heart during pregnancy or shortly after giving birth have better recovery rates than any other group of heart failure patients. This study suggests that fetal stem cells may help human mothers, as well as mice, recover from heart damage."

Tuesday, November 22, 2011
A New York Times piece from earlier in the month: "Is physical frailty inevitable as we grow older? That question preoccupies scientists and the middle-aged, particularly when they become the same people. Until recently, the evidence was disheartening. A large number of studies in the past few years showed that after age 40, people typically lose 8 percent or more of their muscle mass each decade, a process that accelerates significantly after age 70. Less muscle mass generally means less strength, mobility and among the elderly, independence. It also has been linked with premature mortality. But a growing body of newer science suggests that such decline may not be inexorable. Exercise, the thinking goes, and you might be able to rewrite the future for your muscles. ... [researchers] recruited 40 competitive runners, cyclists and swimmers. They ranged in age from 40 to 81. ... There was little evidence of deterioration in the older athletes' musculature, however. The athletes in their 70s and 80s had almost as much thigh muscle mass as the athletes in their 40s, with minor if any fat infiltration. The athletes also remained strong. There was, as scientists noted, a drop-off in leg muscle strength around age 60 in both men and women. They weren't as strong as the 50-year-olds, but the differential was not huge, and little additional decline followed. The 70- and 80-year-old athletes were about as strong as those in their 60s. ... We think these are very encouraging results. They suggest strongly that people don't have to lose muscle mass and function as they grow older. The changes that we've assumed were due to aging and therefore were unstoppable seem actually to be caused by inactivity. And that can be changed."

Monday, November 21, 2011
Why aren't more wealthy people funding aging research? My answer is that wealth does not grant vision, but here is Aubrey de Grey on this topic: "Biogerontology is not your average scientific discipline. It is the study of a phenomenon that currently accounts for two-thirds of all deaths worldwide, and 90% of all deaths within the industrialized world. If measured in terms of suffering or of health care costs, the numbers are equally staggering. As several of my colleagues have noted over many decades, and with increasing energy since the turn of the millennium, the impact of even a modest degree of progress in postponing age-related diseases, as a result of intervening in their common cause (aging), would be immense. ... So why is everyone still oblivious to this disaster? Ultimately, I believe that the answer comes down to just one thing: a failure to appreciate who can potentially benefit from progress. The massive Achilles' heel of biomedical gerontology in terms of appeal to the wider world has always been its focus on lifelong interventions. Those in a position to influence the level of financial support for such work, therefore, are required to start from a position of disenfranchised altruism (since they are already too old to benefit from therapies that need to be begun in youth or earlier). That is a noble position, to be sure, but realistically it is not one that enjoys prolific favor from the public. In particular, it is not a promising target for philanthropy. But the regenerative approach changes all that - indeed, it abolishes it. The whole point of all regenerative medicine is to start with people who are already carrying a significant quantity of damage, which the intervention will then repair. As such, if it can be made to work, rejuvenation biotechnology has the capacity to deliver the substantial (exactly how substantial remains to be seen, but we won't know until we try) postponement of all the debilities that we most fear as we progress toward the age at which we expect our health to fail. And it can deliver it to people who are already in middle age or older by the time the therapies materialize."

Monday, November 21, 2011
You might recall Peter Thiel's advocacy for radical philanthropy, akin to venture investing, wherein high risk high reward projects are funded rather than just the same old staid and conservative institutional funding strategies. This sort of visionary philanthropy seems to be the only way we'll see the groundwork for rejuvenation biotechnology funded to the level at which staid conservative funding sources will agree that it was wonderful all along - and then fund it themselves. Here's a different perspective on the same issue of risk, funding, and institutional biases: "The discovery that aging can be delayed in mice is just the kind of experiment one might suppose would be supported by the National Institutes of Health, the government agency that spends $30 billion a year on financing biomedical research. So after Mayo Clinic researchers discovered they could delay degeneration of the tissues in a fast-aging strain of mice by purging senescent cells, they applied to the agency's National Institute on Aging for financing for the next essential step, that of repeating the test in mice with a normal life span. Under the agency's peer review system, panels of fellow experts judge each proposal and assign it a score. On paper, it's hard to think of a better system. But in practice, experts often differ, even on the best proposals, and a single dissenting vote can reduce a proposal's overall score too low to get financed. The Mayo proposal got a less than perfect score, and was denied money. ... Their peer review process is not promoting innovative, high-risk research. ... They were able to get their research started only because private funds were available from the Ellison Medical Foundation, supported by Larry Ellison of the Oracle software company, and from Robert P. Kogod, a philanthropist in Washington. After publication of the Mayo Clinic team's paper in Nature this month, they were approached by the Glenn Foundation, set up by the commodities trader Paul F. Glenn, who has a longstanding interest in aging research. The foundation gave them an unsolicited $60,000 and said it would be around to talk later." You'll recognize a number of those names as supporters of the SENS Foundation.



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