Fight Aging! Newsletter, October 3rd 2011

October 3rd 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!



- October 5th is the Next SENS Foundation Los Angeles Meeting
- The Prospects for Repairing the Aged Adaptive Immune System
- Input of the Next Round of Fight Aging! Site Changes
- Some of the Roots of the Tithonus Error
- Discussion
- Latest Headlines from Fight Aging!


I'm a little late in passing this on, I realize, but if you're in the Los Angeles area this week you might consider dropping in on the SENS Foundation meeting on Wednesday. Instructions on how to RSVP are in the following Fight Aging! post:

"It's been a long time, since the last occasion that we got together! We at the SENS Foundation have been very busy working harder than ever to take our accomplishments to the next level, and it's been very fruitful. We would like to share this with you in this very special gathering in a most delightful setting. This will be an exceptional occasion, we will be very lucky to have our CSO, Dr. Aubrey de Grey, presenting some important remarks, as well as our CEO Mike Kope giving an extraordinary presentation. On top of this, we will have special guest Ms. Sonia Arrison, author of the book '100 Plus - How the coming age of longevity will change everything, from Careers and Relationships to Family and Faith.' She will engage in a conversation with Aubrey about her new book. Each attendee will get a free copy, and she will be happy to sign it!

"The SENS Foundation has a growing presence at both ends of California. As you might know, the Foundation's research center is in the Bay Area, and a number of the research institutions in California have both a strong interest in aging research and ties to the Foundation. Some of the folk formerly participating in research at the Foundation are even a part of the biotech side of California start up culture nowadays. Which is not to mention the presence of philanthropist Peter Thiel and his interest and connections in longevity science, and a range of other interested supporters. Connections and relationships are what make the world go round, and one purpose of the ongoing series of Los Angeles meetings is to help enlarge that web of support so to better enable the future growth of the SENS Foundation - and alongside it the new field of rejuvenation biotechnology."


The progressive failure suffered by the aged adaptive immune system are somewhat different in character to much of the rest of aging, and this may mean that meaningful repair is closer to being realized:

"The adaptive immune system remembers all threats, but has a limit to the number of cells it can produce; eventually too much of its quota is taken up by memory cells and too little by cells that are actually equipped to destroy things. A small range of persistent but otherwise mostly harmless viruses, such as cytomegalovirus (CMV), greatly speed up this process by hanging around for decades and constantly provoking the immune system into uselessly devoting ever more memory cells to their existence. There are a range of possible ways to deal with this issue, with varying levels of complexity, cost, and permanence: adding more cells cultured from the patient's own stem cells, destroying the unwanted memory cells using targeted therapies of the sort under development in the cancer research community, and so forth. One of the presentations given at the SENS5 conference discusses the latest research in this area."

Researchers have tested versions of many of the possible ways ahead in mice already, to generally positive results. It is clear that the configuration issues present in an old immune system in mammals can be reversed to a large degree; now the work has to be done on human versions of the most promising approaches.


Development on the Fight Aging! site comes in waves, and there will be another round of changes arriving in due course. If you have thoughts on what you'd like to see accomplished, then let me know by commenting on the post linked below:


The default assumption by a majority of people is still that extending life through medical technology will result in being physically old for longer - an extended period of ever greater disability, and nothing to look forward to:

"The Tithonus Error is one the learned patterns by which people reject life extension out of hand: from roots in childhood and education and stories, a majority of people come to believe that extending life means making people older for longer. Most people have an entirely justified horror of the later stages of degenerative aging, and so the idea of more of that just isn't on the table. The rejection of more life under those terms is instinctive and visceral. This rejection is based on a false premise, however, and all that rational fear of aging is piled atop a single irrational misunderstanding. The goal of all medicine, and especially longevity science, is to enable people to be younger for longer, not older for longer. Aging is nothing but damage, and longevity therapies will be no more than ways to slow, or for preference repair, the accumulation of that damage. A machine with less damage is a machine that works better for longer, not a machine that lingers on its dying gasp for longer. That rational fear of aging is big and powerful, however, and it's been somewhat hard to fight one's way past it to point out that 'older for longer' just isn't going to happen."


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, September 30, 2011
Life science students intern at the SENS Foundation research center in the Bay Area as a part of the Foundation's broader academic initiative, working on the foundations of future rejuvenation therapies. Biotechnology has advanced to the point at which bright graduates can help to meaningfully advance the state of the art, and here is a report from one such: "Sarah Fazal joined our research center team as an intern for the summer. Over the past few months, she worked with our MitoSENS team, primarily verifying the integration of DNA transfected into cells and detecting RNA expression levels. Her efforts contributed greatly to the progress our MitoSENS team has made over recent months, and she presented those results in a poster at our recent SENS5 conference in Cambridge. ... The current project for mitoSENS is allotopic expression, which involves copying the mitochondrial DNA into the nucleus. My project required checking for integration of the DNA transfected into cells, and detecting RNA expression levels. By the end of the summer, I had done this successfully for 4 out of the 13 genes involved in oxidative phosphorylation that are still encoded by mitochondrial DNA. I spent my summer mostly doing PCRs (polymerase chain reaction), DNA and RNA isolations, cell culturing, and gel electrophoresis. I learned to perfect these techniques, to think critically when my results weren't as expected, and to design experiments. My experience at SENS helped shape me into a more confident and better experienced scientist. I would definitely recommend volunteering for this foundation; the experience was educational, the research is open-minded, determined, and bold, and the staff is friendly, welcoming, and helpful."

Friday, September 30, 2011
Rapamycin is known to extend life in mice, so researchers are looking into the mechanisms and possible uses as a therapy for age-related diseases. "Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-β (Aβ). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble Aβ and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression." This research is actually fairly indicative of the field as a whole: mechanisms that are potentially modestly useful as ways to slow aging across life are forced into consideration as late-stage therapies only. This happens because regulators will not permit commercialization of ways to treat aging in otherwise healthy people - they only permit treatments for named diseases. So progress is necessarily sub-optimal where it is permitted at all.

Thursday, September 29, 2011
Here is a different way of looking at the material consequences of living a life that allows you to become obese: "The United States has the highest prevalence of obesity and one of the lowest life expectancies among high-income countries. We investigated the relationship between these 2 phenomena. ... We estimated the fraction of deaths attributable to obesity by country, age, and sex and reestimated life tables after removing these deaths. To allow for a possible secular decline in obesity risks, we employed alternative risks from a more recent period. ... In our baseline analysis, obesity reduced US life expectancy at age 50 years in 2006 by 1.54 years for women and by 1.85 years for men. Removing the effects of obesity reduced the US shortfall by 42% for women and 67% for men, relative to countries with higher life expectancies. Using more recently recorded risk data, we estimated that differences in obesity still accounted for a fifth to a third of the shortfall. ... The high prevalence of obesity in the United States contributes substantially to its poor international ranking in longevity."

Thursday, September 29, 2011
A piece by Aubrey de Grey at the Huffington Post: "as things stand, no amount of insight into age-related pathology can be sufficient to develop outright cures. Some diseases are the end results of aging, just as starvation is the end result of fasting. The nature of aging is such that many age-related infirmities are certain to afflict anyone who lives long enough. And this will remain the case, until a technology is developed which ameliorates the general decrepitude of old age which underlies these diseases. One can, therefore, identify the future direction of medicine by considering the nature of old age itself. What exactly is being taken from us, year after year, from cradle to grave? As time goes by, your hair goes grey, your face gets coarser, you put on weight, you become weaker, more susceptible to disease, and so on. But what do these things have to do with each other? Fortunately, the answer is not so complex as one might anticipate. Most people think of the science of aging as being very incomplete. It is true that aging as a process is not completely understood (biogerontology, the study of aging, involves many competing theories). But the state of disrepair that aging leaves people in can be observed directly, and in great detail. A comparison between two perfect snapshots of old and young tissue would provide us with a very multi-faceted damage report. The aged tissue is riddled with "junk" molecules (by-products of normal metabolic functions) in and between cells, which do not dissipate, not even as the body heals and replenishes itself day in and day out. It would also show an accumulation of unwanted cells, and a depletion of necessary cells. All this damage reduces our tissue function, then our organ function, and eventually it kills us. How this damage accumulates, and how it leads to our demise, are matters of some dispute. But the bare facts of how our tissues alter over time already provide us with enough of a compass with which to chart the future course of medicine."

Wednesday, September 28, 2011
Exercise is generally beneficial to long term health in many ways - though it's somewhat cruel that it's so beneficial for the suffers of conditions that make it hard to exercise: "physical activity improves arthritis symptoms even among obese mice that continue to chow down on a high-fat diet. The insight suggests that excess weight alone isn't what causes the aches and pains of osteoarthritis, despite the long-held notion that carrying extra pounds strains the joints and leads to the inflammatory condition. ... Many cases of arthritis are associated with obesity and inactivity, so [the] researchers set out to determine whether a high fat diet induces knee osteoarthritis, and then whether exercise provides a protective effect. Using two sets of male mice - half fed a high-fat diet and the other fed regular chow - the researchers noted significant differences among the two groups. The mice on the high-fat food gained weight rapidly, processed glucose poorly and had much higher blood levels of molecules that trigger the chronic inflammation associated with osteoarthritis. But when these animals got regular running wheel workouts, many of the harmful effects diminished - even though the mice ate the same high-fat food and shed no weight. Glucose tolerance improved, while the inflammatory response was disrupted among key signaling molecules called cytokines, easing the development of arthritis. If the extra weight on the joints had been the cause of the arthritis, the researchers noted, exercise would have exacerbated the problem. Instead, it helped. ... I don't want to say exercise is turning off that inflammatory signal, it just impairs it." The fat tissue accumulated by the obese is a trigger for inflammation via chemical signaling; weight on joints may not be aggravating arthritis, but the increase to levels of chronic inflammation will do just that. Better to be both exercising and shedding the excess fat than just one or the other.

Wednesday, September 28, 2011
From Popular Science: "Giving cardiac patients a heart of gold nanowires could ensure engineered tissue works like it should, pulsing in unison to make the heart beat. First growing nanowires and then growing heart cells, [engineers] say their new muscle-machine blended heart patch improves on existing cardiac patches, which have trouble reaching a consistent level of conductivity. ... Electrical signals shared among calcium ions dictate when cardiomyocytes contract, making the heart beat. But tissue scaffolds are often made with materials like polylactic acid or alginate, which act as insulators, so the signals are blocked. This makes it difficult to get all the cells in a piece of tissue to coordinate their signals and beat in time, which in turn makes it difficult to build a very big or very effective heart patch. The [rsearch team] gets around this problem by integrating gold, an excellent conductor. They mixed alginate, a gummy substance often used in tissue scaffolds, and grew gold nanowires throughout it. Then they seeded the alginate with cardiomyoctes from rat embryos, and monitored calcium levels to gauge their electrical conductivity. Compared to a typical scaffold system, the gold nanowire cells' conductivity improved by three orders of magnitude."

Tuesday, September 27, 2011
You might recall that RAGE, the receptor for advanced glycation end-products (AGEs), is thought to have a role in Alzheimer's disease - it's a mechanism that can explain some of the diabetes-like risk factors noted for the development of this condition, making it look a lot like a lifestyle disease. Here, researchers look at RAGE vaccines as a possible Alzheimer's therapy: "In Alzheimer's, the amyloid protein can accumulate in the brain instead of being eliminated by the body's natural defenses, nestling between the neurons and forming impassable plaques. Amyloid and the way it gets there could be targets for a new vaccine. ... RAGE, or receptor for advanced glycation endproducts, proteins bind to amyloid and transport it into the brain ... Research has shown that RAGE may also contribute to the inflammation and damage that amyloid causes to the brain's nerve cells. [Scientists are] researching a vaccine that targets RAGE and amyloid by using the body's own immune system to protect against their over-production and eventual build-up. ... Unfortunately, all of the vaccines for Alzheimer's that have been through clinical trials have failed. Part of the reason why could be that they're just not comprehensive enough. Most only target amyloid. Our hope is that by taking a more encompassing approach, we will be more effective. So far, that's exactly what we're seeing in our experiments. ... Early results have shown improved cognition and memory in animal models of Alzheimer's ... We need to move on to larger animal studies. We have a lot we still don't know about the vaccine itself. For example, we know that amyloid and RAGE bind together, but we don't know why the binding creates such a stable complex. We have these end points, but we still don't know some of the basic science that needs to be known so that we can push ahead."

Tuesday, September 27, 2011
A review paper on the roles of oxidative stress in aging, both negative and positive: "Oxidative stress is considered to be a major detrimental factor limiting longevity, as originally postulated in the free radical theory of aging. The oxidative stress leads to accrual of damaged/misfolded proteins, increased mutagenesis rate and inflammation. Ironically, due to its ability to accumulate over time (as it was seen in many neurodegenerative disorders), oxidative damage also emerged as a consequence of longevity per se. The human life-span exceeds that of most mammalian species at least 4 times (median life span records across 900 mammalian species is ~16 years). Importantly, anti-oxidative stress adaptations are not subjects of evolutionary pressure at post-reproductive age, which further contributes to the buildup of oxidative damage in aging individuals. Yet, paradoxically, in short-lived Caenorhabditis elegans, oxidative stress might have beneficial effect on longevity by connecting to the nutrition signaling pathways [such as those activated through calorie restriction]. It was suggested that aging is driven by over-activation of signal-transduction pathways such as the nutrient-sensing pathway, while oxidative stress may be both one of its activators and effectors."

Monday, September 26, 2011
From In Search of Enlightenment: "On this WHO website the fact that chronic disease killed 9 million people under the age of 60 last year is highlighted. This is of course a human tragedy that should be mitigated. That is twice the number of deaths estimated to be caused by all injuries in the world. However, if you do the math on this data, that means that 27 million people worldwide died from chronic disease that is caused (primarily, though the story is complex) by aging. This is 75% of the world's chronic disease burden. Aging is the leading cause of disease and death in the world today. ... Not only that, it is the largest health threat today. In just a decade of the chronic diseases of aging the world's population will suffer more more disease and death than in any decade of the worst wars and conflicts in human history. Everyone agrees that conflict and war is bad for us, and that our governments should strive to ensure there is lasting peace between nations. And yet few people today realize how important it is that our governments also support the science and innovation that could modulate the rate of biological aging, thus keeping our bodies and minds healthy for as long as possible. If we hope to make a serious dent on the tsunami of chronic disease that will afflict the 2 billion people worldwide who will be over age 60 by the middle of this century we need to prioritize the study of the biology of aging. Only by retarding the process of cellular and molecular decline can we hope to delay, and possibly compress, chronic disease in the foreseeable future." The post is generally on the right side of the line insofar as the demographics are concerned; you may or may not agree with the political view and reach for government as the agency of first resort.

Monday, September 26, 2011
Via ScienceDaily: researchers "have turned back the clock on mature muscle tissue, coaxing it back to an earlier stem cell stage to form new muscle. Moreover, they showed in mice that the newly reprogrammed muscle stem cells could be used to help repair damaged tissue. The achievement [opens] the door to the development of new treatments to combat the degeneration of muscle associated with muscular dystrophy or aging. ... Muscle formation has been seen as a one-way trip, going from stem cells to myoblasts to muscle fiber, but we were able to get a multi-nucleated muscle fiber to reverse course and separate into individual myoblasts. For many years now, people have wanted to do this, and we accomplished that by exposing the tissue to small molecule inhibitor chemicals rather than altering the cell's genome. ... These tiny chemicals go inside the cell and change the way the cell behaves without changing its genome. The inhibitors were only used for 48 hours, enough time for the fused myofibers to split into individual cells, and then they were washed away. The cells can proceed to live and die as normal, so there is no risk of them dividing uncontrollably to become tumors. ... rather than going back to a pluripotent stage, we focused on the progenitor cell stage, in which cells are already committed to forming skeletal muscle and can both divide and grow in culture. Progenitor cells also differentiate into muscle fibers in vitro and in vivo when injected into injured leg muscle. ... To test the viability of the newly regenerated myobasts, the researchers first cultured them in the lab to show that they could grow, multiply and fuse normally into new myofibers. The researchers then injected the de-differentiated myoblasts into live mice with damaged muscles. ... After two to three weeks, we checked the muscle and saw new muscle fibers that glowed green, proving that the progenitor cells we derived from mature muscle tissue contributed to muscle repair in vivo in mice."



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