Fight Aging! Newsletter, June 6th 2011

June 6th 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!



- Open Cures at h+ Magazine
- The Immune Response Accelerates Aging
- Insight into Funding for Aging Research
- A Few Legal Aspects of Cryopreservation
- Discussion
- Latest Headlines from Fight Aging!


An introduction to the Open Cures initiative is published at h+ Magazine:

"When we look at work on aging and longevity in the laboratory, we can see that more than a dozen ways to use biotechnology to extend the lifespan of mice have been demonstrated over the past decade. About half of those methods appear to lack serious side-effects, delivering only longer lives, lower cancer risk, improved health and vigor, and little else. Similarly, a range of laboratory demonstrations conducted since the turn of the century have reversed specific, measurable biological changes that occur with age in mice: damaged mitochondrial DNA replaced throughout the body, the function of cellular garbage collection mechanisms restored to youthful levels in liver tissue, and so on. We live in an era of rapidly improving biotechnology - and it is delivering the goods, in the laboratory at least.

But there is one common theme to all of these advances: none are undergoing further development for clinical use in healthy humans for the purpose of slowing or reversing degenerative aging, and thereby extending healthy life span. Why is this? You would imagine, given the size of the market for medicine, that a hundred start-up biotech companies would be leaping upon these opportunities, giving rise to an era in which 'anti-aging' fakes and frauds finally start to fade away in favor of a market built upon true rejuvenation science. This is not happening, however, as there is a gargantuan roadblock that stands in the way."

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Fighting off infections and other pathogens comes at a cost: increased levels of subtle biological damage that shorten our life expectancy. One of the reasons we live longer than our ancestors is that the level of infection suffered in youth has fallen dramatically.

"When you look at the reliability theory of aging, or any like consideration of aging as the consequences of accumulating damage to a complex system, it becomes clear that the immune system is an important component in the model. For example, it is generally accepted that much of the improvement in life expectancy over past centuries stems from a reduction in infectious disease - a process that is by no means complete, given what we still suffer from quiet, persistent infections like cytomegalovirus. But fewer infections mean less activation of the immune system in early life and less damage carried into later life. That leads to both improved health, a physiologically younger body at a given chronological age - and an immune system that declines more slowly, and later in life."


Aging research is not a well-funded endeavor, considered in the grand scheme of things.

"Aging research is the poor cousin of the life science field, despite the fact that the overwhelming majority of the harm brought to humanity through disease, frailty, and death is basically caused by aging. Work on extending life or reversing aging is in turn the poor cousin in the aging research family. This situation must change for the better if we are to see meaningful progress in our lifetimes. [This state of affairs reflects] a society that has not yet woken up to decide that repair of aging is in fact both a possibility and a priority. The feedback loop of education from scientists to the public and support from the public to scientists isn't yet running well for longevity science - it is running better than it was a decade ago, but clearly there is much work to be done."


Cryonics, the preservation of your brain - and thus the fine structure that forms the data of your mind - after death, presently requires a lot more work from the customer than other, related services like life insurance:

"As I've noted in the past, one of the challenges that faces present day cryonics as an industry is that it requires a measure of proactive organization and ongoing effort on the part of customers. You can't just sign up for cryopreservation, pay your monthly dues, and let matters coast along unattended - not if you want things to go smoothly when the service is needed. All sorts of obstacles, both organizational and bureaucratic, can rear their ugly heads: arranging your own cryopreservation is less a matter of agreeing to go to a party than it is a matter of agreeing to be the host and organizer of a party.

"This, of course, greatly reduces the range of people who are willing to sign up for cryonics - no-one likes inconvenience, and there's a certain irrationality when it comes to using (or avoiding) inconvenient services that may save your life one day. There is, I think, an opportunity here for some service provider to emerge and offer a more managed cryonics membership, in which these issues are are smoothed away in return for a higher membership cost. But perhaps that lies ahead, in a future in which the cryonics industry grows much larger than it is today.

"But back to the challenges: many of them are legal in nature, or involve the intruding hand of local government. For example, a coroner may wish to conduct an autopsy, which will certainly spoil the chance of a successful cryopreservation. Working through the legal niceties to ensure that the local coroner's office cannot do this is one amongst many line items that must be addressed - and addressed well, as it's not as though you will be up and able to talk your way through any problems that happen at the time."


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, June 3, 2011
The BBC here looks briefly at the study of aging in varying animal species - it mangles the scientific details in the usual fashion, but covers much of the territory: "From the moment they are born into the dense jungle of Central Africa, the biological clock is ticking for baby bonobos. A recent study, published in the journal Science, revealed that all primates - from men to monkeys - roughly age in the same way, with a high risk of dying in infancy, a low risk of dying as juveniles and then an increasing risk of dying as they aged. Some species though, have found a few tricks to help them play the aging game and extend their natural lifespans. By doing so, they can live for hundreds of years. While a select few, by some definitions, may already have become immortal. ... some species of bat [can] live for decades [and] the explanation may lie in the way bats protect themselves from protein damage, using special molecules called protein chaperones. ... Studies of the American lobster (Homarus americanus), have shown that its extreme longevity might be related to the expression of telomerase ... High concentrations of telomerase are found in cells that need to divide regularly such as organs and embryonic stem cells. Access to an elevated supply of telomerase would equip this crustacean with the ability to rebuild cells damaged by aging. The ability to repair cells in this way may help to explain why lobsters can live up to 100 years and are able to regrow limbs even at an 'old age'. ... Another oceanic resident, the quahog clam (Arctica islandica), is thought to be one of the longest lived metazoans of all. A recent study on this ancient clam, [which] lives more than 400 years, shows it has an increased resistance to oxidative stress. ... The reasons for the exceptional longevity in Arctica may have little to do with resistance to oxidative stress though. ... Instead, like in naked mole rats, it may be the integrity of the animal's proteins that may be the key, rather than damaging free radicals or antioxidants used to defend against them."

Friday, June 3, 2011
An example of the how advances in biotechnology are allowing medicine to move closer towards intervening in first causes at the biochemical level: researchers "have developed a new approach for identifying the 'self' proteins targeted in autoimmune diseases such as multiple sclerosis, diabetes and rheumatoid arthritis. ... errant immune responses which mistakenly target the body's own proteins rather than foreign invaders can now be examined in molecular detail. Further research could lead to new insights into the exact causes of these debilitating autoimmune disorders. ... The immune system, the body's main line of defense against disease, has a critical responsibility to distinguish self-derived proteins from those of invaders like viruses and bacteria. Autoimmune diseases arise when a person's immune system fails to make that critical distinction and mistakenly attacks a normal tissue, such as nerve, joint, or insulin-producing pancreatic cells. ... Knowledge of the self-antigens involved in autoimmune processes is important not only for understanding disease etiology, but also for developing diagnostic tests. In addition, physicians may someday use antigen-specific therapies to destroy or disable auto-reactive immune cells. ... But looking through the haystack of cellular complexity for those single-needle self-antigens targeted by the immune system has proved daunting, to say the least. Ideally, scientists would be to develop some kind of biological magnet that could pull these fine needles out of the mass. In this report, the researchers describe an approach which does just that."

Thursday, June 2, 2011
From the SENS Foundation: "For Max, working at the [SENS Foundation Research Center (SENSF-RC)] has been the culmination of years of dedicated study and preparation. Before he first heard about SENS in early 2005, he wasn't a scientist at all; in fact, he was a 23-year-old cost accountant. When he wasn't studying for his MBA, he was counting other people's money. He knew that he wanted more out of life, though: specifically, he wanted to change the world in a way that would benefit society. As soon as he found and read Aubrey de Grey's Ending Aging, he settled on human health as the area he would strive to impact - and on SENS as the way to make that impact. Over the next few years he committed himself to working in finance, at one point teaching at a local community college, always with the intention of saving his money so that he could return to school to learn about science and laboratory work. During this period he studied whenever he had the time, reading articles relevant to health and aging in scientific journals. In 2008, Max went back to school full-time at the University of Toledo to study chemistry, math, and biology. He was interested in taking an active role in SENS research as quickly as he could, so he contacted the predecessor of the SENS Foundation Academic Initiative, MFURI. As a member of the Initiative, he performed a literature review on the harm caused by iron and aluminum accumulation in the body, citing well over a hundred journal articles. Max's paper was accepted by the journal Rejuvenation Research and published in April 2010, just as he was completing his coursework at Toledo. As his next step, Max opted to join the RC staff rather than pursue a PhD opportunity so that he could continue to make as direct and immediate of a contribution to SENS as possible. Max has now been working at the SENSF-RC for one year, and will be staying on to continue his work on the A2E degradation project. In the long term, he hopes to see the LysoSENS project through all of its pre-clinical stages. It is his wish that this work will lead to therapies that can effectively reverse, or at the least greatly slow, the pathology of age-related macular degeneration."

Thursday, June 2, 2011
An interesting discovery: "Reprogramming of somatic cells to a pluripotent state was first accomplished using retroviral vectors for transient expression of pluripotency-associated transcription factors. This seminal work was followed by numerous studies reporting alternative (non-insertional) reprogramming methods, and various conditions to improve the efficiency of reprogramming. These studies have contributed little to an understanding of global mechanisms underlying reprogramming efficiency. Here we report that inhibition of the mTOR (mammalian target of rapamycin) pathway by rapamycin or PP242 enhances the efficiency of reprogramming to induced pluripotent stem cells (iPSCs). Inhibition of the insulin/IGF-1 signaling pathway, which like mTOR is involved in control of longevity, also enhances reprogramming efficiency. In addition the small molecules used to inhibit these pathways also significantly improved longevity in Drosophila melanogaster. We further tested the potential effects of six other longevity-promoting compounds on iPSC induction, including two sirtuin activators (resveratrol and fisetin), an autophagy inducer (spermidine), a PI3K (phosphoinositide 3-kinase) inhibitor (LY294002), an antioxidant (curcumin) and an AMPK (activating adenosine monophosphate-activated protein kinase) activator (metformin). With the exception of metformin, all of these chemicals promoted somatic cell reprogramming, though to different extents. Our results show that the controllers of somatic cell reprogramming and organismal lifespan share some common regulatory pathways, which suggests a new approach for studying aging and longevity on the basis of the regulation of cellular reprogramming."

Wednesday, June 1, 2011
Hormesis is the process by which a little damage or stress to our biology can lead to a longer life span, as it wakes up the repair mechanisms and makes them do a better job than they otherwise would - a net gain in resiliency. Here is a review that summarizes the implications for much of mainstream research into aging and longevity: "Various nutritional, behavioral, and pharmacological interventions have been previously shown to extend life span in diverse model organisms, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mice, and rats, as well as possibly monkeys and humans. This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote increased formation of reactive oxygen species (ROS). These serve as molecular signals to exert downstream effects to ultimately induce endogenous defense mechanisms culminating in increased stress resistance and longevity, an adaptive response more specifically named mitochondrial hormesis or mitohormesis. Consistently, we here summarize findings that antioxidant supplements that prevent these ROS signals interfere with the health-promoting and life-span-extending capabilities of calorie restriction and physical exercise. Taken together and consistent with ample published evidence, the findings summarized here question Harman's Free Radical Theory of Aging and rather suggest that ROS act as essential signaling molecules to promote metabolic health and longevity." ROS can of course be acting both as useful signals and sources of damage in different circumstances - the fact that life can be extended by antioxidants specifically targeted to mitochondria, coupled with the evidence mentioned above, suggests that much.

Wednesday, June 1, 2011
A review paper: "Aging is a gradual process during which molecular and cellular processes deteriorate progressively, often leading to such pathological conditions as vascular and metabolic disorders and cognitive decline. Although the mechanisms of aging are not yet fully understood, inflammation, oxidative damage, mitochondrial dysfunction, functional alterations in specific neuronal circuits and a restricted degree of apoptosis are involved. Physical exercise improves the efficiency of the capillary system and increases the oxygen supply to the brain, thus enhancing metabolic activity and oxygen intake in neurons, and increases neurotrophin levels and resistance to stress. Regular exercise and an active lifestyle during adulthood have been associated with reduced risk and protective effects for mild cognitive impairment and Alzheimer's disease. Similarly, studies in animal models show that physical activity has positive physiological and cognitive effects that correlate with changes in transcriptional profiles. According to numerous studies, epigenetic events that include changes in DNA methylation patterns, histone modification and alterations in microRNA profiles seem to be a signature of aging. Hence, insight into the epigenetic mechanisms involved in the aging process and their modulation through lifestyle interventions such as physical exercise might open new avenues for the development of preventive and therapeutic strategies to treat aging-related diseases."

Tuesday, May 31, 2011
An open access review of work on regenerative medicine based on embryonic stem cells: "The prospect of repairing or replacing damaged, dysfunctional or missing cells with new functional cells has shifted the therapeutic paradigm toward restoring tissue function in individuals affected with aging-associated diseases. The primary candidate for the development of these therapies is stem cells, particularly human embryonic stem cells (hESC), which have the capacity to self-renew indefinitely and differentiate into all tissue-specific cell types... In this review, we will describe the derivation, maintenance, and properties of pluripotent hESCs. We will also outline the methods used to induce the generation of specific cell types from hESCs, with primary focus on cell types that are applicable in understanding the pathology, as well as a potential source of cell-based therapies, in aging-associated diseases. ... As cell replacement therapies are envisioned and realized, their use in the treatment of aging-associated diseases becomes a compelling prospect. hESCs provide much promise as a potential tool in designing such therapies, as well as in drug discovery. It is clear that there are still major scientific challenges as well as ethical and legislative issues that must be addressed. However, it is encouraging to see that clinical trials involving the use of hESCs have begun, and that extensive efforts are underway to efficiently, successfully, and safely differentiate hESCs into specific cell types. These studies will pave the way toward leveraging the therapeutic benefit of hESCs for regenerative medicine, particularly in aging-associated diseases."

Tuesday, May 31, 2011
As you might recall, manipulation of RasGrf1 extends life in mice: "The most intriguing finding was that the complete elimination of normal RasGrf1 increased both average and maximal longevity independent of a role in cancer. We found this to be surprising ... The effect of RasGrf1 deletion on aging, which is also accompanied by lower frailty and retention of motor control, appears to be mediated by greater protection against oxidative damage as observed by lower brain lipid peroxidation, liver protein oxidation and maintenance of the brain and liver glutathione redox potential. We must note that the use of malondialdehyde levels as a measure of overall lipid peroxidation in whole tissues is rather suspect and subject to numerous artifacts; nevertheless, the approximate 25% lower MDA levels in RasGrf-/- mice (in comparison with wild-type mice) were significant. ... it is impressive that the old RasGrf1 deletion mutants exhibited almost 30% lower levels of oxidized liver proteins than did the young wild-type mice. ... RASGRF1 is expressed in pancreatic β-cells where it regulates β-cell mass. So the effects on glucose metabolism is unsurprising. RasGrf1 is also expressed in the hippocampus and hypothalamus is involved in learning and memory. So, one wonders how a human without RasGrf1 would be able to do those functions and whether living longer and stronger might be accompanied by not remembering why one cared. ... Another interesting point raised by the authors is that RasGrf1,which is an exclusively paternal allele imprinted gene, suggests that only the male parent determines the effect of this gene's expression on longevity. In several ways, the RasGrf1-/- mice metabolically resemble mice fed a calorie-restricted diet. One exciting outcome of these studies is that RasGrf1 may be a potential target for design of agents that prolong lifespan and healthspan without the obvious difficulty of restricting caloric intake."

Monday, May 30, 2011
Here's an interesting study that might place some upper bounds on the benefits of exercise accruing to longevity by looking at a cohort of the most highly trained and fit athletes. There are potential selection effects here, however - it's possible that only those already predisposed towards longevity on the grounds of general resiliency tend to become highly trained and fit athletes: "It is widely held among the general population and even among health professionals that moderate exercise is a healthy practice but long term high intensity exercise is not. The specific amount of physical activity necessary for good health remains unclear. To date, longevity studies of elite athletes have been relatively sparse and the results are somewhat conflicting. The Tour de France is among the most gruelling sport events in the world, during which highly trained professional cyclists undertake high intensity exercise for a full 3 weeks. Consequently we set out to determine the longevity of the participants in the Tour de France, compared with that of the general population. We studied the longevity of 834 cyclists from France, Italy and Belgium who rode the Tour de France between the years 1930 and 1964. Dates of birth and death of the cyclists were obtained on December 31 2007. We calculated the percentage of survivors for each age and compared them with the values for the pooled general population of France, Italy and Belgium for the appropriate age cohorts. We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners. Our findings underpin the importance of exercising without the fear that becoming exhausted might be bad for one's health."

Monday, May 30, 2011
Some mainstream media attention for the work of the SENS Foundation: "Rather than simply slowing ageing down, which is what most people have been focused on, we are interested in reversing ageing. So taking people who are already in middle age or older and [getting them back to] the same state of health as a young adult. ... [SENS Foundation co-founder Aubrey de Grey was in Dublin] to talk about how he thinks science will achieve that. ... So how do you reverse ageing? The basis of de Grey's argument is that our metabolism, that complex biochemical orchestra that keeps our bodies running, has side effects that cause damage in the long term. ... The big insight that governs our work is that we can classify these many different types of damage into just seven major categories. And within each category, there is a particular approach that seems promising to not simply slow it down but repair the damage, so we have less of it than we had before the therapy was started. ... The research is at a basic stage, and therapies for use on humans are decades away, according to de Grey. He considers the theme that looks to tackle junk that accumulates between cells to be the most advanced. That's an area being looked at by Dr Brian O'Nuallain, who has just left University College Dublin for Harvard Medical School, and Brigham and Women's Hospital. He is starting work on a Sens-funded project into an age-associated condition called senile systemic amyloidosis. One aim is to develop an antibody that will pick up when a protein called transthyretin clumps abnormally in heart tissue, which can lead to organ failure. Being able to diagnose this early would maximise the beneficial effects of future therapies for the incurable condition,"



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