Fight Aging! Newsletter, October 31st 2011

October 31st 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 Need for a Carl Sagan Figure
- A Look at Russia 2045
- Aubrey de Grey at the MIT Club of Northern California
- An Introduction to Cancer Stem Cells
- Surgeries are Not a Desirable Goal
- Discussion
- Latest Headlines from Fight Aging!


Why is astrophysics such a popular field of science? Is there something here that we advocates for the development of rejuvenation biotechnology can learn from?

"Here's a question for you: why does the triumvirate of astrophysics, astronomy, and cosmology get such good press and widespread public approval in comparison to, say, the fundamental life sciences? I have to think it has something to do with the succession of scientists who evolved into successful media figures, educators, and advocates for their field, such as Carl Sagan, the present day Neil deGrass Tyson, or Patrick Moore - and I'm probably dating myself here by knowing of the existence of the latter. If asked to name noted scientists who went on to become media figures, off the cuff, I think I'd be hard pressed to quickly come up with more than one or two who didn't come from an astrophysical or similar background (right now my brain is delivering Attenborough, Dawkins, and blank). So clearly there's been a lot of groundwork accomplished over the past decades: bringing the broad field of physics and cosmology to the masses, and along the way gaining public support for the ongoing and often thankless work of understanding the universe and its myriad components."


A novel initiative from the Russian portion of the longevity advocacy community recently caught my eye:

"Folk from the Russian side of the longevity advocacy and transhumanist communities have initiated a range of interesting ventures and perspectives in the past few years. Take KrioRus, for example, or the work of the Science for Life Extension Foundation. Following in the same vein, I see that at the recent Singularity Summit the founder of an interesting new initiative called Russian 2045 presented his view on the best path for longevity science, mixed in with a heady brew of can-do Russian sci-tech nationalism - an attitude that might instill a certain nostalgia for the recent past of American technological exceptionalism in the older readers here.

"To my eyes, the most interesting aspect of this Russia 2045 initiative is that, unlike any other serious proposal I'm aware of, their focus is on getting out of biology and into machine bodies as rapidly as possible. Bear in mind that in the long term every plan for radical life extension ends up with we humans changing out our biological parts for machinery - but that is generally proposed to happen somewhere past the point at which nanotechnology supersedes biology in terms of effectiveness, when there is increasingly little difference between biological and nanoscale machine systems. Both operate on the scale of single molecules, but the artificial system will be much better at it than the natural system - because it will be designed rather than evolved. We will replace our biology with machinery because the machinery will ultimately get the job done much more effectively. Until that time arrives, however, much of the longevity science movement focuses on biotechnology, medicine, and the development of other ways to keep the biology we have repaired and in good shape. Not so for Russia 2045, however."


SENS Foundation co-founder recently presented at the MIT Club of Northern California, and you can view video of the proceedings at the following Fight Aging! post:


"Dr. de Grey has been a provocative and polarizing figure in the scientific and medical communities' dialogue on the topic of life extension, and the approaches that will
lead to dramatic increases in quantity and quality of life. According to Dr. de Grey, 'the first human who will live up to 1,000 years is probably already alive now, and might even be today between 50 and 60 years old.'"


The existence of cancer stem cells provides the tantalizing hope that there are commonalities in cancer sufficiently broad to allow a single form of therapy to be effective for many types of cancer:

"The cancer stem cell hypothesis suggests that a majority of cancers are driven and supported by a small population of errant stem cells, and that these cells are characteristic in ways allowing them to be identified and destroyed. Without the cancer stem cells, a cancer would whither. In other words, cancer stem cells offer the hope that there are in fact broad commonalities in the mechanisms of different forms of cancer, and that this fact will lead to a unified, single technology platform and robust cures for even late-stage cancers. The existence and universality of cancer stem cells is a hotly debated topic in medical research, and rightly so for the reasons given above. Good evidence and arguments can be found on either side. Is cancer something that can be solved through a single mechanism or group of very similar mechanisms? Or only some cancers? Or only few cancers? These are important questions, and the answers, when they arrive, will tell us whether the prospects are for many cures arriving soon or for a slow and incremental flow of therapies over decades."


The future of medicine for the old should not involve major surgeries:


"The present work on tissue engineering of large structures, such as printing blood vessels and organs, or creating patient-specific organs for transplant using decellularization, will produce end results that rely on surgery - major surgical procedures in the case of organ transplants. The trouble with surgery is that it is risky: major, involved surgeries bear a non-trivial risk of death even in the most advanced clinical surroundings, and that risk grows with age. Old people suffer a general frailty due to the damage of aging that makes it progressively less likely for them to survive any given surgical procedure. When you consider that every major organ is going to have issues if we live long enough without access to general biological repair technologies that remove the cellular and molecular damage that lies at the root of tissue dysfunction in aging, that's a bunch of major surgeries to look forward to.

"So I believe we should look on the forthcoming phase of tissue engineering as a transitional period: organs will be built from scratch and transplanted until such time as the state of the art allows our existing organs to be incrementally repaired and rebuilt in situ instead. Eliminating the need for surgery is a big deal, and so in the long term I think that the future belongs to the branch of regenerative medicine that delivers populations of tailored stem cells into damaged tissue. As the research community becomes every better at precisely controlling the behavior and activities of cells, even that step of delivering new cells into the body may go away, to be replaced with adaptive drug-like therapies that issue commands to the body's existing cells through signaling pathways or induced epigenetic alterations, and which react to guide the ongoing state of repair."


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, October 28, 2011
The opening up of information, communication, and organization brought by the internet is changing business as normal in every field, making it far easier for ideas on the edge to gain support and activity. This is important for the development of rejuvenation biotechnology, as the changing nature of scientific work can speed the move to the mainstream, and allow for far more useful progress to be achieved while the flow of funding is still comparatively small: "our entire model of education and what it means to be a 'trained professional' is shifting. There's a hell of a lot of resistance from the status quo - which makes it difficult and inconvenient for rapid progress - but it isn't enough to stop it from happening. ... When the university system and the current PhD paradigm was invented, it was a different time. ... If you wanted to study advanced topics, or apprentice under someone famous to learn from their expertise, you needed to go to a university. But things are different now. Technology allows us access to some of the leading minds of our age [making] proximity to a university campus nearly irrelevant in order to meet other students and benefit from valuable peer-to-peer discussions. With the world's information available on the web, and with all of these advances in technology allowing for rapid data sharing and collaboration, how much value is there in the Ivory Tower? We are becoming a society of autodidacts, with information at our fingertips 24/7. Citizen Science is a natural consequence of that. Have an interesting scientific inquiry? Get on the web and investigate it. Learn from the millions of sources out there. Crowdsource some ideas, generate some hypotheses. Have discussions with others. Make a plan. Get your equipment. The scientific method is in-progress. Science is free for all to explore. Why waste time jumping through bureaucratic hoops when you can begin investigating what you want, when you want? Need to fund your research? Crowdsourced methods of funding, such as Kickstarter, are becoming more popular for these types of endeavors. Instead of 100 scientists chasing the same grant, why not go to the public and let them fund what they think is valuable? I think we'll be seeing a lot more of this in the future."

Friday, October 28, 2011
Another review of Sonia Arrison's 100+: "I have to congratulate Sonia Arrison on putting together a book that is both highly accessible to newbies with no prior background in transhumanist thinking or longevity research, and also richly interesting to those of us who have playing in these regions of conceptual space for a long time. The main concepts in the book are indeed things I've been familiar with for a long time: (a) There is a host of rapidly accelerating technologies with the apparent capability of dramatically extending human healthspan, (b) Most likely, human psychology and society will adapt to dramatically increased human healthspan as it occurs, so that it will be experienced primarily as a Good Thing rather than as something traumatic or troublesome However, the book is packed with a sufficient number of interesting informational tidbits, that I found it well worth reading in spite of my general familiarity with the biology, psychology and sociology of radical longevity. ... Arrison reviews the key technological streams leading us toward radically increased healthspan - including gene therapy, stem cell therapy, Aubrey de Grey's SENS concept, artificial organs, tissue regeneration, the potential application of advanced AI to longevity research, and so forth. Both current research and envisioned future advances are considered. Then, in what is probably the greatest strength of the book, she considers the potential psychological and social impact of progressively increasing healthspan: the effects, as the book's subtitle indicates, on personal life, family relationships, marriage, careers and the economy etc. Combining common sense with appropriate invocations of rigorous research and statistics, Arrison provides the most systematic refutations I've seen of the standard anti-longevity arguments - 'death gives life meaning', 'overpopulation will starve or bankrupt us all', and so forth. Step by step, and in an invariably good-natured and friendly way, she demolishes these arguments, making a solid case that increased healthspan is likely improve rather than degrade our emotional health and family lives and enhance our careers and economies."

Thursday, October 27, 2011
A number of different research teams have recently demonstrated epigenetic markers that can be used to establish chronological age or predict life expectancy to various degrees. Here is another: "Aging has been associated with accumulation of cellular defects such as DNA damage and telomere shortening. On the other hand, there is accumulating evidence that aging rather resembles a developmentally regulated process which is tightly controlled by specific epigenetic modifications. ... All tissues of the organism are affected by aging. This process is associated with epigenetic modifications such as methylation changes at specific cytosine residues in the DNA (CpG sites). Here, we have identified an Epigenetic-Aging-Signature which is applicable for many tissues to predict donor age. ... This Epigenetic-Aging-Signature was tested on a validation group of eight independent datasets corresponding to several cell types from different tissues. ... The average absolute difference between predicted and real chronological age was about 11 years. ... It has to be noted, that chronological age is not identical with biological age and it is conceivable that some of the discrepancy between predicted and real age can be attributed to this difference - further research might facilitate determination of the biological age for personalized medicine."

Thursday, October 27, 2011
There are a number of different lines of research focused on developing artificial blood or culturing blood to order from stem cells: "Clinical trials using blood created from adult stem cells are set to begin within the next two or three years, raising the prospect it could soon become routinely used where real blood is unavailable. Scientists are also developing alternative bloodlike substances which could be injected into the body as a 'stopgap' until an actual blood transfusion could be performed. ... modern doctors have minimised the risk of patients receiving infections such as Hepatitis A and C during transmission [but] blood produced from stem cells would avoid these risks and could be manufactured as type 'O-negative', which is produced by just 7 per cent of the population but is suitable for use in into up to 98 per cent of patients. ... It could also be used in certain hospital situations, for example in elective surgery, and save hundreds of thousands of lives in parts of the world where blood banks are not available. [Researchers have] developed a method of taking adult stem cells from bone marrow and growing them in the laboratory to produce cells which look and act almost identically to red blood cells. Once their technique is fine-tuned the team may consider using stem cells taken from embryos, or reprogrammed skin cells, instead of adult cells because although the end product does not mimic red blood as closely, they can be grown in much greater quantities in the lab. ... A more radical solution, which [researchers] say could be perfected within five to 10 years, is to develop a completely artificial alternative to blood which performs the same key functions and would be safe to use in patients of every blood type. This could involve packing haemoglobin - which carries oxygen around the body - into a synthetic cell-like structure, or using a chemical to hold the haemoglobin together so that it can be injected without the need for red blood cells."

Wednesday, October 26, 2011
The SENS Foundation has published a series of posts over the past year or so that follow progress in the development of immunotherapies to remove the age-related buildup of amyloid in the brain - much of it intended as treatments for Alzheimer's disease. Success here will, however, lead to a broader technology platform that might ultimately be turned against any damaging aggregate that builds up in the body with age. These aggregates contribute to aging itself, and so removing them is one necessary part of any comprehensive rejuvenation biotechnology package: "soluble and insoluble aggregates of beta-amyloid protein (Aß) and other malformed proteins accumulate in brain aging and neurodegenerative disease, leading progressively to neuronal dysfunction and/or loss. These have long been widely accepted to be drivers of Alzheimer's disease (AD) and other age-related dementias and neurological disorders such as Parkinson's disease, and it has recently become increasingly clear that neuronal protein aggregates are the main driver of 'normal' cognitive aging. To prevent and reverse the course of neurodegenerative disease and age-related cognitive dysfunction, the regenerative engineering solution is therapeutic clearance of extracellular aggregates (such as Aß plaques) and intracellular aggregates (such as soluble, oligomeric Aß). Immunotherapeutic Aß clearance from the brain is a very active field of Alzheimer's research, with at least seven passive, and several second-generation active, Aß vaccines currently in human clinical trials. ... . We now have a published report of preliminary findings from the first Phase I trial in an Aß-targeting vaccine with novel properties, and with the benefit of preliminary findings of outcomes that have only emerged with the experience of its forerunners in previous clinical trials."

Wednesday, October 26, 2011
Via ScienceDaily: "Exceptional cognitive and physical function in old age leaves a tell-tale immunologic fingerprint, say researchers ... Likewise, older adults who have mild impairments bear a distinct immunologic pattern, too. ... Our study indicates that getting older does not necessarily mean that the immune system gets weaker, as many of us assumed. The immune system is dynamic, and the changes it undergoes over time very much influence function. ... For the project, the team collected blood samples from 140 participants who had been followed in the Cardiovascular Health Study (CHS) for nearly two decades and were 78 to 94 years old. With only two participants younger than 82, the average age of the group was 86. The team also gathered information about the participants' health and function, medical history and hospitalizations, and self-rated health, and assessed their cognitive and physical function using standard tests. Previous research has shown that with age, immune cells called T-cells become more like natural killer (NK) cells, which typically target tumor cells and virus-infected cells ... A closer look in the new study shows that participants who were most physically and cognitively resilient had a dominant pattern of stimulatory NK receptors on the T-cell surface, and that these unusual T-cells can be activated directly through these NK receptors independently of the conventional ones. The functionally resilient elders also have a distinct profile of blood proteins called cytokines that reflect an immune-enhancing environment. ... Conversely, the group that showed mild health impairment had a dominant pattern of inhibitory NK receptors on their T-cells, and they have a cytokine profile indicating a pro-inflammatory environment. Both of these immunologic features could suggest a greater susceptibility to illness."

Tuesday, October 25, 2011
Work on sirtuins as longevity genes hasn't exactly shown promise, but there are still interesting things to be learned from the work taking place, as this open access paper shows: "One fundamental observation in cancer etiology is that the rate of malignancies in any mammalian population increases exponentially as a function of age, suggesting a mechanistic link between the cellular processes governing longevity and carcinogenesis. In addition, it is well established that aberrations in mitochondrial metabolism, as measured by increased reactive oxygen species (ROS), are observed in both aging and cancer. In this regard, genes that impact upon longevity have recently been characterized in S. cerevisiae and C. elegans, and the human homologs include the Sirtuin family of protein deacetylases. Interestingly, three of the seven sirtuin proteins are localized into the mitochondria suggesting a connection between the mitochondrial sirtuins, the free radical theory of aging, and carcinogenesis. Based on these results it has been hypothesized that Sirt3 functions as a mitochondrial fidelity protein whose function governs both aging and carcinogenesis by modulating ROS metabolism. Sirt3 has also now been identified as a genomically expressed, mitochondrial localized tumor suppressor."

Tuesday, October 25, 2011
The degree to which progressive mutation of nuclear DNA causes aging is debated, but here is some work on the mechanisms: "Genetic damage through mutations and genome rearrangements has been hypothesized to contribute to aging. The specific mechanisms responsible for age-induced increases in mutation and chromosome rearrangement frequencies and a potential causative role for DNA damage in aging are under active investigation. Retrotransposons are mobile genetic elements that cause insertion mutations and contribute to genome rearrangements through nonallelic recombination events in humans and other organisms. We have investigated the role of endogenous Ty1 retrotransposons in aging-associated increases in genome instability using the Saccharomyces cerevisiae chronological aging model. We show that age-induced increases in loss of heterozygosity and chromosome loss events are consistently diminished by mutations or treatments that reduce Ty1 retrotransposition. Ty1 mobility is elevated in very old yeast populations, and new retromobility events are often associated with chromosome rearrangements. These results reveal a correlation between retrotransposition and genome instability during yeast aging. Retrotransposition may contribute to genetic damage during aging in diverse organisms and provides a useful tool for studying whether genetic damage is a causative factor for aging."

Monday, October 24, 2011
A layperson's explanation of the theorized role of mitochondria in driving aging can be found at h+ Magazine: "Aging is a complex process that, by nearly all educated accounts, appears to involve multiple different interacting processes. Aubrey de Grey has sought to break down the causes of aging into seven categories; others have presented different understandings. One perspective on aging broadly recognized as important, however, is the mitochondrial theory - tying aging to changes in the function of mitochondria, the energy powerhouses of the cell. This article reviews the mitochondrial theory of aging, with an aim of describing enough of the science to give the lay reader a real sense of what the theory is about. ... In the mid-1950s, Denham Harman proposed that aging results from accumulated damage inflicted by free radicals - atoms or molecules possessed of a sole unpaired electron in their outer shells. ... In 1972 Harman proposed the Mitochondrial Theory of Aging (MTA), which is considered an extension of the free radical hypothesis. According to this theory, aging is due to the cumulative effects of damage wrought by free radicals on the mitochondrial DNA and function. ... Taken together, data derived from several thousand studies largely supports the MTA. Mitochondrial fee radicals damage the mitochondrial DNA, causing mitochondrial dysfunction with lowered ATP production, cellular energy depletion and death, resulting in aging."

Monday, October 24, 2011
From Singularity Hub: "scientists, engineers, futurists, and other forward-thinkers converged for Singularity Summit 2011. ... In this first part of three [we'll] highlight the speakers who discussed the various aspects of health related to the singularity. This includes life extension and regenerative medicine as well as the implications of these new technologies. ... Hands down, one of the most exciting talks of the first day. Dr. Stephen Badylak was able to wow the crowd with his work on regenerative medicine ... Working at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, Badylak and his team have been experimenting with what's known as the extracellular matrix (ECM), the structural component in animal tissue outside of the cells. Research has found that besides providing support for cells, the ECM acts as a 'information superhighway', allowing cells to communicate with each other. Part of this communication involves molecular signals that recruit stem cells after injury and indeed, grafting pig ECM at sites of human injury have been shown to work better at regenerating tissue than injecting stem cells directly. ... Dmitry Itskov presented on a new movement that he has founded to tackle the issue of human immortality. Itskov gave a somewhat nationalistic presentation, touching on many aspects of why Russia is poised to become the leader in the area of longevity. He described the work of famous Russian scientists that are the intellectual grandfathers of this movement and gave an open invitation to anyone who wanted to help grow it. As was a common theme throughout the 2-day summit, Itskov doesn't think that the breakthroughs in the technology to bring radical life extension to market will necessarily come from government. Instead, he advocates grass-roots movements [that] assemble the necessary scientists, thinkers, and financiers to see it through."



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