FIGHT AGING! NEWSLETTER
February 13th 2012
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 New Organ Mprize
- One Wealthy Zealot Would Make a 20 Year Difference
- An Interview on Very Small Embryonic-Like Stem Cells
- SENS5 Video: Collective Advantages of Life Extension
- Latest Headlines from Fight Aging!
THE NEW ORGAN MPRIZE
The New Organ Mprize site is looking good:
"Imagine a future where no one has to suffer and die while waiting for an organ that never arrives. New Organ funds that future. With your help, everyone who needs an organ can have one custom made for them from their own cells. A crowd funded prize to award the team that creates the first complex organ - heart, lung, pancreas, liver, or kidney - from a person's cells. Banking: Preserve a complex organ for 30 days. Thousands die because the best we can do is less than a day. Engineering: Build a complex whole organ from a person's cells, transplant it, and have it function for two years."
If you support these goals, then I note that there is currently a matching fund for donations: a pledge drive to raise the first $200,000 by the end of March. They have raised more than $45,000 in pledges this year - so do your part and help! In a world in which a Kickstarter project can pull in a million dollars for an iPhone widget, I'd like to think that it's also possible to rapidly raise a few hundred thousand dollars for a cause that actually matters.
ONE WEALTHY ZEALOT WOULD MAKE A 20 YEAR DIFFERENCE
Why are there no wealthy zealots?
"Something to think about: outstanding success for the SENS Foundation and its mission would look something like the assured availability of $100-300 million for research and development. That much money tends to build the successes and cachet needed to attract more of the same. To get to this point from where the Foundation stands now (a yearly budget around $1 million for the SENS Foundation, and an unknown but likely smaller level of unaffiliated funding for the same goals) might take twenty years of steady growth and success, with the end result being a substantial persuasion and conversion of the present research and funding culture for medical development. That wouldn't mean that the SENS Foundation would be a $100 million giant, or even necessarily still exist, but it would give rise to a diverse and competitive community that inherits the founders' values and goals - to defeat aging by building rejuvenation biotechnology more or less as presently envisaged in the SENS platform.
"So what happens if a fellow with a net worth of $100-300 million becomes a zealot for the cause, overnight perhaps, and decides to put his net worth behind the SENS cause because without life and health, what is money? I use the world zealot in the best possible way here: someone who values the cause greatly enough to spend more time and money than most other people consider reasonable - but in this case is entirely justified, given the present harms caused by aging. But what happens if the community acquires such a zealot? To my eyes it looks like we would gain two decades of headway, and projects that would otherwise languish for twenty years would commence immediately. In a pattern of growth that is limited only by the level of investment - which is exactly where rejuvenation biotechnology is today - everything in the timing hinges on when the money arrives.
"The interesting question is why this doesn't happen: there are a fair number of very wealthy people in the world, and logic suggests that the best possible use for much those resources from their individual perspectives would to buy more life - since we are now in an age in which it is possible to make a run at buying significantly more life. What is wealth to the sick or the dead when it comes to it? But I don't think that this is a "why don't more people support engineered longevity?" sort of a question. My suspicion is that it is not just longevity science that looks in vain for wealthy zealots, but that in general any grand cause that people can feel very strongly about also lacks wealthy zealots. It seems to me that there is in fact little overlap between the small population of zealots for a cause, people willing to devote their working life and significant resources to a grand project, and the small population of very wealthy people, those with a net worth of $100 million and up.
"We can speculate as to why this might be. ... he passion for the process that will make a person wealthy takes up the much the same mental space as the passion for a cause: there are only so many hours in the day, and only so much attention that a person can give to any one set of information. So you are unlikely to see a person who has (a) accomplished the necessary devotion to work and process for a shot at becoming very wealthy, but also (b) put in the necessary work and process to become a zealot. Or to put it yet another way, neither becoming exceedingly wealthy nor becoming a zealot are things that just happen one day out of the blue. They are each a fair way down their own different paths of effort, realization, and specialization."
AN INTERVIEW ON VERY SMALL EMBRYONIC-LIKE STEM CELLS
One of the researchers involved in categorizing very small embryonic-like stem cells in recent years was interviewed for h+ Magazine:
"Very small embryonic like stem cells (VSELs) are purified from adult tissues and are potential sources of stem cells for application in regenerative medicine and stem cell therapies. ... A question that is important from the developmental point of view is why pluripotent stem cells, (PSCs) such as VSELs, would reside in adult organs? For many years, it had been accepted that adult tissues contain only tissue-committed stem cells (TCSCs) that have limited possibility of differentiation - for example, epidermal stem cells, hematopoietic stem cells, skeletal muscle stem cells. ... I am deeply convinced that regenerative medicine is our key to a better life and our key to extending lifespan. I believe that we will be able to employ [pluripotent stem cells] (e.g., VSELs), isolated from adult tissues, to harness stem cells to regenerate damaged organs. In combination with developing scaffold-technologies, we may be able to generate ex vivo organ fragments or even whole organs and replace organ transplantations with in vitro generated ones."
SENS5 VIDEO: COLLECTIVE ADVANTAGES OF LIFE EXTENSION
Another of the many interesting presentations from last year's SENS5 conference is uploaded in high definition video:
"There are more economic benefits to enhanced human longevity than just the obvious ones. Some of these benefits emerge from systematic changes in the interactions and relationships that make up society: the willingness to consider longer time horizons changes the way in which people value all sorts of things, both in the present and for the future. If fifty years from now is someone else's problem in your eyes, you are unlikely to be a good steward of fifty-year bonds - but if you are going to be alive, vocal and very much in the picture five decades from now, then the way in which you look at these things becomes completely different. You can substitute forests, farmland, houses, familial relations, companies, or a range of other entities for the fifty-year bonds there: we humans instinctively put a value on everything, and there's nothing wrong with that. The more that people value their relationships, possessions, future earnings, and a hundred other line items, the more willing they are to invest in maintaining these tangible and intangible entities.
"This incentive to invest and improve is important, because short-termism is the road to ruin in all things economic - and everything that we do is in the general sense an economic decision. All wealth and civilization is built upon the move away from short-termism, to depart from the practice of strip-mining the present because you believe you are unlikely to benefit from the future. As the expectancy of human life increased over the past few centuries, so the time horizons of our ancestors broadened, and they became more likely to take actions that increased wealth: planning for the long term, investing in technology and research, trading rather than war, and building rather than tearing down."
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!
LATEST HEADLINES FROM FIGHT AGING!
ILLUSTRATING BROKEN INCENTIVES
Friday, February 10, 2012
Research is fundamentally broken by regulation in much of the world. One facet of this problem is that the cost of obtaining approval for new drugs and technologies is so astronomical that large swathes of the research community are directed towards finding marginal new uses for drugs that are already approved by regulators. This activity is, despite occasional successes like the one linked here, always going to be far less productive and useful than tailoring new technologies to the problem at hand. This is one of many ways in which regulation slows progress to a grinding crawl. Because people only pay attention to the occasional successes, they don't see or much care about the many other potential successes that never happened and were never worked on because of the perverse financial incentives put upon the research community by the regulators: "Bexarotene has been approved for the treatment of cancer by the U.S. Food and Drug Administration for more than a decade. These experiments explored whether the medication might also be used to help patients with Alzheimer's disease, and the results were more than promising. ... the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. [Researchers] chose to explore the effectiveness of bexarotene for increasing ApoE expression. The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors (RXR), which control how much ApoE is produced. ... The present view of the scientific community is that small soluble forms of amyloid beta cause the memory impairments seen in animal models and humans with the disease. Within six hours of administering bexarotene, however, soluble amyloid levels fell by 25 percent; even more impressive, the effect lasted as long as three days. Finally, this shift was correlated with rapid improvement in a broad range of behaviors in three different mouse models of Alzheimer's."
Friday, February 10, 2012
This short post at Business Insider serves as a reminder of two items. Firstly, the author notes that 'Silicon Valley billionaires are pouring money into gene research and modifications' - and I wish that were the case! There are very few philanthropists and investors amongst the wealthy of the technology industry who are doing this, and Peter Thiel and Larry Ellison are outliers in having devoted millions to this end. Journalists who cover the tech industry sometimes wake up momentarily to see instances of the comparatively rare funding of longevity science - and then assume it to be more commonplace than it is. In fact, progress in this field is absolute limited and determined by the lack of funding for programs like SENS: the path ahead is very clear, and availability of funds for the research and development is the bottleneck. The second point is illustrated by glancing at the article comments, in which we can see that it is still very much the cultural norm to decry efforts to extend healthy life - and to be expected to decry efforts to extend healthy life, to conform to this view or suffer censure. Consider this for a moment: we still live in a society in which the mainstream view is that people must suffer horribly and die on schedule, and to do anything about that is wrong. Personally, I blame much of that required-attitude-in-public on the pervasive influence of Malthusian, hair shirt environmentalism, coupled with some of the less pleasant aspects of human nature in all of us. For the foreseeable future this is the great act of persuasion we must undertake: convince a large segment of the population to agree in public that we can use biotechnology to do away with the suffering of old age, and that we should use biotechnology to do away with the suffering of old age.
SPARC AND CHANGES IN MUSCLE STEM CELLS WITH AGE
Thursday, February 9, 2012
Researchers are steadily cataloging the details of age-related changes in stem cells, which seem to have as much to do with the cellular environment as a whole as the cells themselves: "Aging causes phenotypic changes in skeletal muscle progenitor cells (SMPCs) that lead to the loss of myogenicity and adipogenesis. Secreted protein acidic and rich in cysteine (SPARC), which is secreted from SMPCs, stimulates myogenesis and inhibits adipogenesis. The present study aimed to examine whether changes in SPARC expression, its signaling pathway, or both are involved in age-related phenotypic changes in SMPCs. SPARC expression levels were comparable in SMPCs derived from young and old rats. However, when SPARC expression was reduced by a SPARC-specific siRNA, SMPCs from young rats showed reduced myogenesis and increased adipogenesis. In striking contrast, old rats showed little changes in these functions. ... These results suggest that, although SPARC plays a role in regulating SMPC function, SMPCs become refractory to the action of SPARC with age. Our data may explain an age-related shift from myogenesis to adipogenesis, associated with sarcopenia. ... Because SPARC enhances myogenesis and inhibits adipogenesis, we reasoned that its decreased expression or alterations in its signaling pathway in SMPCs contribute to age-related dysfunction of skeletal muscle, such as fatty infiltration and impaired muscle regeneration. The present study shows that the SPARC signaling pathway, rather than the level of its expression in SMPCs changes with age. It should be noted skeletal muscle cell types other than SMPCs, such as myofibers and endothelial cells, express SPARC. Moreover, SPARC expression levels decline with age in the skeletal muscles of mice. This indicates that although SPARC expression in SMPCs is not altered with age, the amount of SPARC available in the SMPC microenvironment would be decreased. Thus, it is possible that in addition to the decreased responsiveness of SMPC to SPARC, the age-related decline of SPARC expression levels in skeletal muscle accelerates age-related phenotypic changes in SMPC."
FASTING VERSUS CANCER
Thursday, February 9, 2012
As researchers continue to explore calorie restriction, intermittent fasting, and other forms of lowering food intake, then make discoveries like this: "Man may not live by bread alone, but cancer in animals appears less resilient, judging by a study that found chemotherapy drugs work better when combined with cycles of short, severe fasting. Even fasting on its own effectively treated a majority of cancers tested in animals, including cancers from human cells. ... For example, multiple cycles of fasting combined with chemotherapy cured 20 percent of mice with a highly aggressive type of children's cancer that had spread throughout the organism and 40 percent of mice with a more limited spread of the same cancer. No mice survived in either case if treated only with chemotherapy. Only a clinical trial lasting several years can demonstrate whether humans would benefit from the same treatment. ... As with any potential cancer treatment, fasting has its limits. The growth of large tumor masses was reduced by multiple fasting and chemotherapy cycles, but cancer-free survival could not be achieved. [Researchers] speculated that cells inside a large tumor may be protected in some way or that the variety of mutations in a large mass may make it more adaptable. ... The cell is, in fact, committing cellular suicide. What we're seeing is that the cancer cell tries to compensate for the lack of all these things missing in the blood after fasting. It may be trying to replace them, but it can't. ... A way to beat cancer cells may not be to try to find drugs that kill them specifically but to confuse them by generating extreme environments, such as fasting that only normal cells can quickly respond to."
β-AMYLOID BUILDS UP IN ALL OF US
Wednesday, February 8, 2012
Like many age-related conditions, Alzheimer's disease results from an excess in processes of degeneration that are common to all of us. We all have β-amyloid building up in our brains, and we are all being damaged by it (or by the underlying causes that lead to it) - just to a lesser extent. A practical therapy for Alzheimer's that works by removing causes of aggregate buildup is something that everyone would benefit from: "Several lines of evidence suggest that pathologic changes underlying Alzheimer disease (AD) begin years prior to the clinical expression of the disease, underscoring the need for studies of cognitively healthy adults to capture these early changes. The overall goal of the current study was to map the cortical distribution of β-amyloid (Aβ) in a healthy adult lifespan sample (aged 30-89), and to assess the relationship between elevated amyloid and cognitive performance across multiple domains. ... Aβ deposition is distributed differentially across the cortex and progresses at varying rates with age across cortical brain regions. A subset of cognitively normal adults aged 60 and over show markedly elevated deposition, and also had a higher rate of APOE ε4 (38%) than nonelevated adults (19%). Aβ burden was linked to poorer cognitive performance on measures of processing speed, working memory, and reasoning. ... Even in a highly selected lifespan sample of adults, Aβ deposition is apparent in some adults and is influenced by APOE status. Greater amyloid burden was related to deleterious effects on cognition, suggesting that subtle cognitive changes accrue as amyloid progresses."
SPEEDING UP THE REPAIR OF BROKEN BONE
Wednesday, February 8, 2012
News of "fracture putty," an evolution in the use of scaffold material for bone regeneration: recent studies "show promise to significantly shorten the healing time and revolutionize the course of fracture treatment. ... Healing of critical-size defects is a major challenge to the orthopedic research community. Large-bone defects must be stabilized and necessitate technologies that induce rapid bone formation in order to replace the missing tissue and allow the individual to return to rapid function. To date, no single material can suffice. ... In our experiences with large animal models, following the guidelines established by our animal care and use committee, we have been successful in formulating a product that contains mesenchymal stem cells and allows them to survive in the environment of the fracture long enough to elicit the rapid formation of new bone. ... To start the bone regeneration process, the [researchers] used adult stem cells that produce a protein involved in bone healing and generation. They then incorporated them into a gel, combining the healing properties [into] 'fracture putty.' [The] team used a stabilizing device and inserted putty into fractures in rats. Video of the healed animals at two weeks shows the rats running around and standing on their hind legs with no evidence of injury. [The] researchers are testing the material in pigs and sheep, too. ... Our approach is biological with the putty. Other groups are looking at polymers and engineering approaches like implants and replacements which may eventually be combined with our approach. We are looking at other applications, too, using this gel, or putty, to improve spinal fusion outcomes."
ANOTHER STUDY ON EXERCISE AND TELOMERE LENGTH
Tuesday, February 7, 2012
If you think that telomere length is a secondary marker of aging and health, then it makes perfect sense that exercise would lengthen telomeres. There is ample evidence to show that average telomere length, while declining with age, is somewhat dynamic in response to circumstances, at least in the white blood cells examined by most present day research: "Leukocyte telomere length (LTL) is a potential indicator of cellular aging; however, its relation to physical activity and sedentary behavior is unclear. The authors examined cross-sectionally associations among activity, sedentary behavior, and LTL among 7,813 women aged 43-70 years in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992 and sedentary behavior in 1992. Telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative polymerase chain reaction. ... For total activity, moderately or highly active women had a 0.07-standard deviation (SD) increase in LTL compared with those least active. Greater moderate- or vigorous-intensity activity was also associated with increased LTL ... Associations remained after adjustment for body mass index. ... Although associations were modest, these findings suggest that even moderate amounts of activity may be associated with longer telomeres, warranting further investigation in large prospective studies."
MORE ON EXERCISE AND MUSCLE STEM CELLS
Tuesday, February 7, 2012
As you might imagine, exercise affects the behavior of muscle stem cells: "researchers determined that an adult stem cell present in muscle is responsive to exercise, a discovery that may provide a link between exercise and muscle health. The findings could lead to new therapeutic techniques using these cells to rehabilitate injured muscle and prevent or restore muscle loss with age. Mesenchymal stem cells (MSCs) in skeletal muscle have been known to be important for muscle repair. ... Since exercise can induce some injury as part of the remodeling process following mechanical strain, we wondered if MSC accumulation was a natural response to exercise and whether these cells contributed to the beneficial regeneration and growth process that occurs post-exercise. ... The researchers found that MSCs in muscle are very responsive to mechanical strain. They witnessed MSC accumulation in muscle of mice after vigorous exercise. Then, they determined that although MSCs don't directly contribute to building new muscle fibers, they release growth factors that spur other cells in muscle to fuse and generate new muscle, providing the cellular basis for enhanced muscle health following exercise. ... Next, the group hopes to determine whether these cells contribute to the decline in muscle mass over a person's lifetime. Preliminary data suggest MSCs become deficient in muscle with age. The team hopes to develop a combinatorial therapy that utilizes molecular and stem-cell-based strategies to prevent age-related muscle loss."
DIRECTING STEM CELLS TO ENHANCE BONE STRENGTH
Monday, February 6, 2012
Osteoporosis is a pervasive issue in the old, and potential methods for reversing its effects are welcome: scientists have "developed a novel technique to enhance bone growth by using a molecule which, when injected into the bloodstream, directs the body's stem cells to travel to the surface of bones. Once these cells are guided to the bone surface by this molecule, the stem cells differentiate into bone-forming cells and synthesize proteins to enhance bone growth. ... There are many stem cells, even in elderly people, but they do not readily migrate to bone. Finding a molecule that attaches to stem cells and guides them to the targets we need is a real breakthrough. ... The researchers made use of a unique hybrid molecule, LLP2A-alendronate ... The researchers' hybrid molecule consists of two parts: the LLP2A part that attaches to mesenchymal stem cells in the bone marrow, and a second part that consists of the bone-homing drug alendronate. After the hybrid molecule was injected into the bloodstream, it picked up mesenchymal stem cells in the bone marrow and directed those cells to the surfaces of bone, where the stem cells carried out their natural bone-formation and repair functions. ... Twelve weeks after the hybrid molecule was injected into mice, bone mass in the femur (thigh bone) and vertebrae (in the spine) increased and bone strength improved compared to control mice who did not receive the hybrid molecule. Treated mice that were normally of an age when bone loss would occur also had improved bone formation, as did those that were models for menopause." This is an example of the future of stem cell medicine - more about directing and altering stem cells in the body to create in-situ effects than providing new cells or growing tissue for transplant.
AUTOPHAGY VERSUS PROGERIA
Monday, February 6, 2012
Enhancing autophagy, the cellular housekeeping processes that recycle damaged components and proteins, is one of the possible approaches under investigation for treating a range of age-related conditions and modestly slowing aging. The accelerated aging condition progeria is caused by malformed lamin A, an important structural protein in cells. An accumulation of bad lamin A is something that also occurs in normal aging, albeit to a much lesser degree. Here, researchers propose turning autophagy to remove the damaged lamin A: "Farnesylated prelamin A is a processing intermediate produced in the lamin A maturation pathway. Accumulation of a truncated farnesylated prelamin A form, called progerin, is a hallmark of the severe premature ageing syndrome, Hutchinson-Gilford progeria. Progerin elicits toxic effects in cells, leading to chromatin damage and cellular senescence and ultimately causes skin and endothelial defects, bone resorption, lipodystrophy and accelerated ageing. Knowledge of the mechanism underlying prelamin A turnover is critical for the development of clinically effective protein inhibitors that can avoid accumulation to toxic levels without impairing lamin A/C expression, which is essential for normal biological functions. Little is known about specific molecules that may target farnesylated prelamin A to elicit protein degradation. Here, we report the discovery of rapamycin as a novel inhibitor of progerin, which dramatically and selectively decreases protein levels through a mechanism involving autophagic degradation. Rapamycin treatment of progeria cells lowers progerin, as well as wild-type prelamin A levels, and rescues the chromatin phenotype of cultured fibroblasts ... Importantly, rapamycin treatment does not affect lamin C protein levels ... Thus, rapamycin, an antibiotic belonging to the class of macrolides, previously found to increase longevity in mouse models, can serve as a therapeutic tool to eliminate progerin."