Fight Aging! Newsletter, August 22nd 2011

August 22nd 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!



- You Pays Your Money, You Takes Your Chances
- Checking Up on Sirtris
- Another Path to Partial Immune System Rejuvenation
- SENS Foundation is Hiring an IT Resource
- Discussion
- Latest Headlines from Fight Aging!


In this life the only certain thing is risk. Your job - in health as in everything else - is to manage that risk as best possible, not to look for certainties:

"What happens across your lifetime to change you from young to old is known as stochastic damage - the integrity of your bodily systems nibbled away, one damaged or misplaced clump of atoms at a time. At the detail level of molecular machinery, this is basically random. But the process is statistically predictable when you start to look at the bigger picture: our bodies are all, sadly, headed downhill in much the same general direction, and we can even talk about trends, environmental factors, and speeds of decline when we examine large groups of people.

"For you, personally, what this means is that you have a ticket to ride and you can steer the bounds of the possible by your actions. But there's no such thing as absolute control - there are only risks to be shifted one way or another. Laze around and grow fat, and watch the risk of diabetes, cancer, and dementia grow much larger. Or smoke and suffer the likely consequences. Or avoid doctors like the plague for two dozen years and you're making your own bad luck, slowly but surely.

"Some people sail through all that exactly because they were lucky, or both lucky and possessed of rare protective genes. Equally, you could do everything right, live the healthiest life possible, and get nailed by cancer in your twenties, or by the sudden onset of an unsuspected genetic condition in your thirties, or by an autoimmune disease despite no history of it in your family. Or, hell, by some idiot operating heavy machinery without a license while you're minding your own business on the sidewalk. These things happen. They're rare, but the point is that they're on the ticket: all you can do is swing the odds.

"In some things we can make our own luck; in others we can't. Not much that can be done today about the bolt from the blue cancer in your teens, or the genetics that dealt you a heart that'll have to be nursed like the engine in a second hand car for the rest of your life. But for the rest of it: the prepared and the foresighted have what looks like great luck in life - at least from the perspective of people who didn't pay attention to all the groundwork that led to that point."


Sirtris Phamaceuticals was briefly back in the news recently with the latest results from a mouse study of one of their drug candidates:

"So what is Sirtris up to these days? The startup was founded to investigate a line of calorie restriction mimetic compounds based on sirtuin biochemistry, and acquired for a very large sum by GlaxoSmithKline. The hope was that something to modestly slow aging would emerge - though even if so, development would be sidelined into making a therapy for diabetes or something similar, as the FDA outright forbids the commercial development of therapies to treat aging. A sad state of affairs in the land once known and the land of the free, to be sure, but it is what is.

"Unfortunately for Sirtris, though not for their early investors, little of practical use has so far emerged from their work. It looks very much like the best case end result will indeed be something like a drug candidate to alleviate some of the consequences of obesity, diabetes or metabolic syndrome, all conditions that the vast majority of sufferers could have avoided through leading a healthier lifestyle, and could still reverse by leading a healthier lifestyle. Given the state of the world today, a medicine like that may yet make a great deal of money for GlaxoSmithKline, but it's not going to do anything of significance for human life spans. So, on the whole, the money poured into Sirtris looks like a failure wearing the clothes of success - and the more so because a bunch of people are going to see that researchers and investors made out like bandits from the deal and follow the same path, rather than trying to do something more ambitious and more useful."


It seems there has been a small flood of progress in the past few years on ways to reverse some of the age-related decay in the immune system. Here is news of another advance:

"Our immune systems get progressively weaker as we age because each time we recover from an infection a proportion of our white blood cells become deactivated. This is an important process that has probably evolved to prevent certain cancers, but as the proportion of inactive cells builds up over time our defences become weakened. What this research shows is that some of these cells are being actively switched off in our bodies by a mechanism which hadn't been identified before as important in ageing in the immune system. Whilst we wouldn't want to reactivate these cells permanently, we have an idea now of how to wake them from their slumber temporarily, just to give the immune system a little boost. ... When the researchers blocked this newly identified pathway in the lab they found that the white blood cells appeared to be reactivated. Medicines which block this pathway are already being developed and tested for use in other treatments so the next step in this research is to explore further whether white blood cells could be reactivated in older people, and what benefits this could bring."


The SENS Foundation is looking to hire a part time IT / web development resource. If this is your area of work and you'd like to help contribute to the future of rejuvenation biotechnology, then here is your chance:

"About the position: The IT Manager will, in the first instance, report to our Director of Research Operations, Tanya Jones. However, the successful candidate will be required to work with all members of staff to consolidate and expand our IT infrastructure, both internal and public-facing. Initial projects will include: migration of email systems from legacy servers; implementation of a collaboration framework for files and documents; a review of our web systems, their integration with finance and customer relations back-ends, and associated social networking sites."


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, August 19, 2011
This is a UK press article on Halcyon Molecular, one of the new companies that has emerged from the pro-engineered-longevity community in recent years. You might also look back in the Fight Aging! archives for more on the views of the founders: "Even by Silicon Valley standards, the grand design drawn up by William and Michael Andregg is hugely ambitious. Halcyon Molecular, the company that the brothers founded in 2008, is developing a way to sequence the human genome - and thus unlock the deepest secrets of DNA - faster and cheaper than ever before. ... William is 29, Michael just a year older, and both are college drop-outs - but given Silicon Valley's impressive track record for nurturing and funding obsessive, unconventional young innovators, their age is hardly unusual. The surprise is the long-term mission of Halcyon Molecular: to solve "the biggest challenge humans can individually face - disease and mortality", as the mission-statement poster in their office reception says. Put another way, they're supercharging the effort to map life's biological code in almost unimaginable digital detail and, by doing so, ultimately, to attempt to conquer death itself." The difference between the here and now and 20 years ago is that you declare your plans to defeat aging and age-related death and both be taken seriously and raise large sums of money for research and development, both inside and outside the scientific community. There has been a sea change in attitudes towards engineered longevity as a goal, and that is one of the reasons that significant progress will be made in the years ahead: things happen when people start earnestly working to make them happen.

Friday, August 19, 2011
An old Fight Aging! post is dusted off, rewritten, and published at h+ Magazine: "I'm not going to try to convince you that the foreseeable future is a wondrous place: either you accept the implications of the present rate of technological progress towards everything allowed by the laws of physics, in which case you've probably thought this all through at some point, or you don't. Life, space travel, artificial intelligence, the building blocks of matter: we'll have made large inroads into bending these all to our will within another half century. Many of us will live to see it even without the benefits of medical technologies yet to come: growing up without the internet in a 1960s or 1970s urban area will be the new 1900s farmboy youth come 2040. Just like the oldest old today, we will be immigrants from a strange and primitive near-past erased by progress, time travelers in our own lifetimes. A century is an exceptional life for a human, but far greater spans of years will be made possible by the technologies of the 21st century. I'll plant a flag way out there on the field and claim a million years ... Despite being out there, the million year life span is not an unsupported pipe dream. Living for a million years is a goal that can be envisaged in some detail today: the steps from here to there laid out, the necessary research and development plans outlined, and the whole considered within the framework of what is permissible under the laws of physics, and what the research community believes can be achieved within the next 20, 50, or 100 years."

Thursday, August 18, 2011
An open access paper on the biology of one of the longest-lived engineered mouse species: "The age-associated decline in tissue function has been attributed to ROS-mediated oxidative damage due to mitochondrial dysfunction. The long-lived Ames dwarf mouse exhibits resistance to oxidative stress, a physiological characteristic of longevity. It is not known, however, whether there are differences in the electron transport chain (ETC) functions in Ames tissues that are associated with their longevity. In these studies we analyzed enzyme activities of ETC complexes, CI-CV and the coupled CI-CII and CII-CIII activities of mitochondria from several tissues of young, middle aged and old Ames dwarf mice and their corresponding wild type controls to identify potential mitochondrial prolongevity functions. Our studies indicate that post-mitotic heart and skeletal muscle from Ames and wild-type mice show similar changes in ETC complex activities with aging, with the exception of complex IV. Furthermore, the kidney, a slowly proliferating tissue, shows dramatic differences in ETC functions unique to the Ames mice. Our data show that there are tissue specific mitochondrial functions that are characteristic of certain tissues of the long-lived Ames mouse. We propose that this may be a factor in the determination of extended lifespan of dwarf mice."

Thursday, August 18, 2011
The SENS Foundation Academic Initiative is a long-term project aimed at helping to build the research community of tomorrow - one interested in the repair and reversal of aging, rather than a next generation that is only interested in slowing down aging a little via manipulation of metabolism, a simple repeat of today's research community. Here is an update from the Foundation: "The SENS Foundation Academic Initiative's new structure is actively in the process of being implemented, and involves a number of significant changes. Among these are the separation of the Initiative into branches, an updated membership system that allows students to become involved more easily and in more ways, the creation of volunteer committees, and the addition of outreach projects to the Initiative's activities. ... There will be three branches: Research, Outreach, and Education. The Research branch will be focused on the actual accomplishment of scientific research. This research will always be done with an eye to publication, but its most important function will be to provide our students with learning experiences, to help them develop into career scientists. The Outreach branch will be focused on spreading the word about the Academic Initiative and about the SENS Foundation, while the Education branch will be focused on educating students about science and SENS. ... While the Academic Initiative has long helped students to complete research projects, it has not done much in the past to encourage students to be advocates of the Initiative and the SENS Foundation. This will change with the implementation of outreach projects. These will generally be simple, off-the-shelf projects that students can finish in an afternoon, such as printing fliers from a pre-made template and distributing them at their university."

Wednesday, August 17, 2011
That part of the research community focused on manipulating metabolism to slow down aging has advanced to the point of considering multiple distinct simultaneous changes to achieve the desired end result: "Modern medicine is directed towards the prevention, detection and cure of individual diseases. Yet, current medical models inadequately describe aging-associated diseases. We now know that failure in longevity pathways including oxidative stress, multisystem dysregulation, inflammation, sarcopenia, protein deposition and atherosclerosis are associated with age-related diseases. Such longevity pathways are potential targets for therapeutic intervention. Interventions in specific pathways have been shown to ameliorate and postpone the aging phenotype by activation of multiple genes. The strategy that we propose in this paper is to apply interventions simultaneously on complementary longevity pathways to achieve a synergistic result. For instance, aging is known to attenuate the HSF1 pathway leading to production of very toxic beta-amyloid fibrils. Consequently, the FoxO pathway is activated, resulting in the formation of less toxic high molecular weight aggregates as a defense mechanism. Thus the simultaneous upregulation of the HSF1 and FoxO pathways could potentially decrease protein deposition and proteotoxicity, thereby retarding or possibly preventing the onset of neurodegenerative diseases. Modulating these two pathways may also delay the onset of other age-related pathologies including cognitive decline, cancer, diabetes and cardiovascular disease due to its multi-gene effect. "

Wednesday, August 17, 2011
Researchers find what looks to be a proxy measure for the degree to which a person is sedentary - but of course there might be other important correlations here, such as with wealth or intelligence: "Watching TV for an average of six hours a day could shorten the viewer's life expectancy by almost five years ...The impact rivals that of other well known behavioural risk factors, such as smoking and lack of exercise, the study suggests. Sedentary behaviour - as distinct from too little exercise - is associated with a higher risk of death, particularly from heart attack or stroke. Watching TV accounts for a substantial amount of sedentary activity, but its impact on life expectancy has not been assessed, say the authors. They used previously published data on the relationship between TV viewing time and death from analyses of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), as well as Australian national population and mortality figures for 2008, to construct a lifetime risk framework. AusDiab is a national survey of a representative sample of the population, starting in 1999-2000, and involving more than 11,000 adults aged 25 or older. The authors then constructed a risk framework for the Australian population in 2008, based on the answers the survey participants had given, when quizzed about the total amount of time they had spent in the previous week watching TV or videos. ... These figures compare with the impact of other well known lifestyle factors on the risk of death from cardiovascular disease after the age of 50, including physical activity and obesity. For example, other research has shown that lifelong smoking is associated with the shortening of life expectancy by more than 4 years after the age of 50, with the average loss of life from one cigarette calculated to be 11 minutes - equivalent to half an hour of TV watching, according to the authors' risk framework." I applaud the researchers for finding a way to present their work that will likely get a lot of play in the media.

Tuesday, August 16, 2011
Gaining a large fraction of the estimated maximum possible long-term benefits from exercising can be achieved with only modest levels of regular exercise according to researchers. This recent paper is representative of earlier, similar findings: "The health benefits of leisure-time physical activity are well known, but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear. We assessed the health benefits of a range of volumes of physical activity in a Taiwanese population. In this prospective cohort study, 416,175 individuals (199,265 men and 216,910 women) participated in a standard medical screening programme in Taiwan between 1996 and 2008, with an average follow-up of 8.05 years. On the basis of the amount of weekly exercise indicated in a self-administered questionnaire, participants were placed into one of five categories of exercise volumes: inactive, or low, medium, high, or very high activity. We calculated hazard ratios (HR) for mortality risks for every group compared with the inactive group, and calculated life expectancy for every group. Compared with individuals in the inactive group, those in the low-volume activity group, who exercised for an average of 92 min per week or 15 min a day, had a 14% reduced risk of all-cause mortality, and had a 3 year longer life expectancy. Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4% and all-cancer mortality by 1%. These benefits were applicable to all age groups and both sexes, and to those with cardiovascular disease risks. Individuals who were inactive had a 17% increased risk of mortality compared with individuals in the low-volume group."

Tuesday, August 16, 2011
A short piece on mitochondria and their role in aging: "Despite propaganda to the contrary, aging is rarely a pleasurable experience. A lifetime of damage to cells and tissues results in malfunction, making old age a significant risk factor for ailments such as cancers and neurologic disabilities typified by Alzheimer's disease. As a consequence, the graying of world populations has triggered a scientific frenzy to unravel the basic processes behind aging and find ways to slow down and perhaps even prevent age-related degeneration. ... Two linked ideas are at the core of our current aging theory. The first is that proteins, RNA and DNA are bombarded with and damaged by reactive oxygen species (ROS) generated during normal cellular respiration and this results in eventual decline and disease. The second is that mitochondria are the major culprits behind aging. ... micro-injection of mitochondria from 'young' cells, those which haven't divided very much, can overcome senescence in cells that are reaching the natural end of their lives and will probably, in the usual course of things, undergo programmed cell death, or apoptosis which is also largely controlled by mitochondria. ... Further support for the 'mitochondrial theory' of aging [comes] from studies in a range of organisms including yeast, nematode worms, flies and mice showing that by silencing certain mitochondrial genes - mitochondria have their own circular genomes - life span is extended."

Monday, August 15, 2011
A lesser but still important detail in tissue engineering is given some thought: "scientists are seemingly approaching a day when they will be able to make nearly any type of tissue from human embryonic stem cells. You need nerves or pancreas, bone or skin? With the right combination of growth factors, skill and patience, a laboratory tissue culture dish promises to yield therapeutic wonders. But within these batches of newly generated cells lurks a big potential problem: Any remaining embryonic stem cells - those that haven't differentiated into the desired tissue - can go on to become dangerous tumors called teratomas when transplanted into patients. Now researchers [have] developed a way to remove these pluripotent human embryonic stem cells from their progeny before the differentiated cells are used in humans. ... We've used a combination of antibodies to weed out the few undifferentiated cells that could be left in the 10 or 100 million differentiated cells that make up a therapeutic dose. ... The researchers studied two sets of antibodies - one commercially available and one they generated themselves - to identify which among them bound most strongly to pluripotent, but not differentiated, cells. They found one newly generated antibody that was highly specific for a previously unknown marker on undifferentiated cells that they termed stage-specific embryonic antigen-5, or SSEA-5. The cells bound by this antibody, anti-SSEA-5, expressed high levels of pluripotent-specific genes and resembled embryonic stem cells in appearance. Anti-SSEA-5 also bound strongly to the inner cell mass of an early human embryo, the group of cells from which embryonic stem cell lines are derived. ... anti-SSEA-5 recognizes and binds to a cell-surface carbohydrate structure called a glycan. As the pluripotent cell differentiates, this glycan is modified to other glycan structures not recognized by the antibody."

Monday, August 15, 2011
A great many interesting demonstrations of tissue engineering have taken place in recent years, and here is another: "Every organ in the human body has a scaffold or a structure, which provides it with its shape, and within this scaffold are many different types of cells with different functions. Tissue engineering aims to create the organ scaffold - either through the use of synthetic materials such as polymers, or through decellularization, which uses the whole organ as a scaffold after removing its cells. Decellularization is ideal for tissue regeneration because it preserves the three-dimensional structure of the organ and the extracellular matrix (ECM) - the framework between the cells - that are complex and difficult to mimic. While current methods use specific ECM proteins to transform stem cells into a particular cell type, scientists have found it difficult to imitate the natural ECM. Using the decellularization approach, a team of [researchers] removed the cells from the heart of a mouse and implanted the empty heart scaffold with [human embryonic stem cells] to observe if these cells could attach to the scaffold and develop into heart cells. After 14 days, the cells developed into two different types of cells found in the heart: cardiac marker expressing cells and endothelial or blood vessel cells. The cell-laden scaffold was then implanted back into the mouse where it was observed to develop visible blood vessels. The formation of blood vessels in the scaffold is critical for the transport of nutrients and oxygen to the heart, and has posed a major challenge in tissue engineering."



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