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!

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CONTENT

- Telomerase Gene Therapy Extends Mouse Lifespan
- The Maintenance Gap
- Resilient Biochemistry in Naked Mole-Rats
- Discussion
- Latest Headlines from Fight Aging!

TELOMERASE GENE THERAPY EXTENDS MOUSE LIFESPAN

Researchers have demonstrated that a genetic alteration previously shown to extend life in mice can be packaged into a gene therapy and used to extend life - though to a lesser degree - in ordinary adult laboratory mice:

http://www.fightaging.org/archives/2012/05/telomerase-gene-therapy-extends-life-eliminates-cancer-in-adult-mice.php

"A few years ago, a Spanish research team created transgenic mice that lived significantly longer than normal by combining increased p53 with increased telomerase. p53 is a cancer suppressor that under usual circumstances reduces the ability of stem cells to replace worn cells in aging tissue - less cell proliferation means a lower chance of cancer over time, but also faster aging as the tissues of the body wear and fail more readily. More telomerase, on the other hand, achieves the opposite end: dynamic, longer lasting cells that also produce way more cancers in the course of their more energetic operations. This, in any case, is the consensus view of how these elements work in the biochemistry of mammals.

"The researchers recently published results for the next stage of their research program: taking the modifications that had been transgenic to date and instead applying them as gene therapies to adult mice. This is a step on the road to building some form of beneficial medical technology for humans ... Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. The therapy, furthermore, produced an appreciable improvement in the animals' health, delaying the onset of age-related diseases - like osteoporosis and insulin resistance - and achieving improved readings on ageing indicators like neuromuscular coordination. The gene therapy utilised consisted of treating the animals with a DNA-modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in ageing. Telomerase repairs the extremes of chromosomes, known as telomeres, and in doing so slows the cell's and therefore the body's biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

"In 2007, [the researchers] proved that it was feasible to prolong the lives of transgenic mice, whose genome had been permanently altered at the embryonic stage, by causing their cells to express telomerase and, also, extra copies of cancer-resistant genes. These animals live 40% longer than is normal and do not develop cancer. The mice subjected to the gene therapy now under test are likewise free of cancer. Researchers believe this is because the therapy begins when the animals are adult so do not have time to accumulate sufficient number of aberrant divisions for tumours to appear."

THE MAINTENANCE GAP

Here is an addition to one of the traditional views of the evolution of aging, considered in the broader context of current strategic directions in the aging research community:

http://www.fightaging.org/archives/2012/05/the-maintenance-gap.php

"Much of the mainstream aging research community has little interest in building therapies for aging, being focused on investigation only - though, fortunately, this situation is changing rapidly these days. The past stigma associated with public discussion of treating and ultimately preventing aging has largely evaporated within the scientific world. Among those researchers who are interested in therapies for aging, most are focused on the slow boat of metabolic alteration: work that will have comparatively little pay-off even if successful, but which fits more readily into established research programs and the prejudices of research funding institutions.

"The principal downside of metabolic alteration strategies, from my point of view, is that even if successful they cannot produce any significant longevity benefit in a person already old. ... There is another disadvantage, which is illustrated by the different degrees to which life span is enhanced by similar strategies applied in mice versus humans. It is taken for granted in the literature, and thus probably not emphasized to the degree it should be, that an extension of life by 50% in mice based on some genetic or metabolic alteration - such as calorie restriction or growth hormone knockout - is probably not going to map to a similar extension of life in humans. If humans could achieve that sort of life extension through simply eating well and eating less or being growth hormone mutants, we'd have known about it by now. Consider Laron dwarfism, for example, or the generation after generation of practitioners of various degrees of calorie restriction that exist in many cultures.

"With an eye to this second disadvantage, I'll point out an open access paper that considers the evolution of aging from the point of view of the maintenance gap. This is the gap between the cost of maintenance required to keep an organism from aging and the resources actually devoted to maintenance - both of which are subject to evolutionary selection pressures, which operate to maximize success in genetic propagation rather than the comfort or longevity of individual members of a species.

"One of the prevailing theories of aging, the disposable soma theory, views aging as the result of the accumulation of damage through imperfect maintenance. Aging, then, is explained from an evolutionary perspective by asserting that this lack of maintenance exists because the required resources are better invested in reproduction. However, the amount of maintenance necessary to prevent aging, 'maintenance requirement' has so far been largely neglected and has certainly not been considered from an evolutionary perspective. ... This has major implications for our understanding of the aging process on both the evolutionary and the mechanistic level. It means that the expected effect of measures to reallocate resources to maintenance from reproduction may be small in some species.

"The point to take away from this argument is that we should expect to find a broad variation between species in their response to similar forms of metabolic and genetic alteration aimed at extending life span. So far that is what is seen, with we humans having the short end of the stick - though obviously there is an ocean of data yet to be obtained on this topic. On the whole, though, it seems like one more slowly building argument for the research community to focus on repair-based strategies for treating aging: build biotechnologies that are explicitly designed to repair forms of biological damage that existing repair systems either cannot handle or handle too slowly. SENS is the most obvious example, though I expect other, competing repair-focused visions to emerge in the years ahead as the SENS Foundation obtains further scientific support and promising research results."

RESILIENT BIOCHEMISTRY IN NAKED MOLE-RATS

The naked mole-rat is becoming a well-studied species:

http://www.fightaging.org/archives/2012/05/resilient-biochemistry-in-naked-mole-rats.php

"Researchers are attempting to find the root causes of cancer immunity and exceptional longevity in this species, with an eye to creating beneficial medical biotechnologies for humans. .. Present theories are varied, but on the longevity side of the house the consensus appears to lean towards an increased resistance to forms of cellular membrane damage - naked mole rat membranes are built of a more resilient mix of proteins than those of comparable species. This is known as the membrane pacemaker hypothesis of aging.

"This mouse-sized mammal lives ∼8 times longer than do mice and, despite high levels of oxidative damage evident at a young age, it is not only very resistant to [cancer] but also shows minimal decline in age-associated physiological traits. ... naked mole-rat fibroblasts are extremely tolerant of a broad spectrum of cytotoxins including heat, heavy metals, DNA-damaging agents and xenobiotics, showing [median lethal dose] values between 2- and 20-fold greater than those of fibroblasts of shorter-lived mice. Our new data reveal that naked mole-rat fibroblasts stop proliferating even at low doses of toxin whereas those mouse fibroblasts that survive treatment rapidly re-enter the cell cycle and may proliferate with DNA damage. Naked mole-rat fibroblasts also show significantly higher constitutive levels of both p53 and Nrf2 protein levels and activity, and this increases even further in response to toxins.

"Enhanced cell signaling via p53 and Nrf2 protects cells against proliferating with damage, augments clearance of damaged proteins and organelles and facilitates the maintenance of both genomic and protein integrity. These pathways collectively regulate a myriad of mechanisms which may contribute to the attenuated aging profile and sustained healthspan of the naked mole-rat. Understanding how these are regulated may be also integral to sustaining positive human healthspan well into old age and may elucidate novel therapeutics for delaying the onset and progression of physiological declines that characterize the aging process."

DISCUSSION

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!

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LATEST HEADLINES FROM FIGHT AGING!

OLD CALORIE RESTRICTED RATS ACT YOUNGER THAN THEIR PEERS
Friday, May 18, 2012
http://www.fightaging.org/archives/2012/05/old-calorie-restricted-rats-act-younger-than-their-peers.php
No great surprise here, given that calorie restriction in mammals slows almost all measures of aging investigated to date: "Long-term caloric restriction (CR) has been reported to extend the life spans, delay the onset and decrease the incidence of a broad spectrum of age-associated diseases. However, its effect on rat explorative behaviour is still unclear. In the present study, a number of behavioural measures were continuously monitored in 3-, 12-, 24-25-, 28-29- and 35-44-month-old male Wistar rats that were fed either ad libitum or placed on a caloric restricted diet. A gradual decline in locomotor activity of the ad libitum fed rats has been determined during aging in the open field test. In the CR groups, 3-month-old rats exhibited lower levels of exploratory behavior, compared to rats on the control diet. 24-25-month-old CR rats exhibited higher levels of exploratory behaviour, compared to ad libitum fed animals of the same age. Chronic dietary restriction nullified the age-dependent decline in locomotor activity and explorative behaviour of rats."

A BRIEF LAYPERSON'S TOUR OF THE PHILOSOPHY OF NONEXISTENCE
Friday, May 18, 2012
http://www.fightaging.org/archives/2012/05/a-brief-laypersons-tour-of-the-philosophy-of-nonexistence.php
It is taken as a tenet around here that involuntary death is a bad thing, and the process of getting to be dead despite your own wishes on the matter is arguably worse - it involves a great deal of ongoing suffering and pain as the body progressively fails. Greatly diminishing the incidence of death is one aim of the longevity science movement, achieved through the elimination of degenerative aging, the greatest cause of death. Can we say why being dead is bad, however? That is supposedly a harder job than declaring suffering to be bad and worthy of amelioration - though most philosophers fail to consider the economic costs of destruction, and in the end it should all come down to "I've decided I don't like it, and so I'll work towards doing something about it through progress in medical science." Reasons beyond personal choice are unnecessary, but here is a brief tour of some of the philosophy of death and nonexistence: "We all believe that death is bad. But why is death bad? In thinking about this question, I am simply going to assume that the death of my body is the end of my existence as a person. But if death is my end, how can it be bad for me to die? After all, once I'm dead, I don't exist. If I don't exist, how can being dead be bad for me? ... there's a puzzle raised by the Roman philosopher Lucretius, who thought it a mistake to find the prospect of my death upsetting. Yes, as the deprivation account points out, after death we can't enjoy life's pleasures. But wait a minute, says Lucretius. The time after I die isn't the only period during which I won't exist. What about the period before my birth? If nonexistence is so bad, shouldn't I be upset by the eternity of nonexistence before I was born? But that's silly, right? Nobody is upset about that. So, he concludes, it doesn't make any sense to be upset about the eternity of nonexistence after you die, either. It isn't clear how best to reply to Lucretius. One option, presumably, is to agree that we really do need to treat those two eternities of nonexistence on a par, but to insist that our prebirth nonexistence was worse than we thought. Alternatively, we might insist that there's an asymmetry that explains why we should care about the one period but not the other. But what is that difference? Perhaps this: When I die, I have lost my life. In contrast, during the eternity before my birth, although I'm not alive, I have not lost anything. You can't lose what you never had. So what's worse about death is the loss."

IGF-1 RECEPTOR VARIATIONS AND SHEEP LONGEVITY
Thursday, May 17, 2012
http://www.fightaging.org/archives/2012/05/igf-1-receptor-variations-and-sheep-longevity.php
Insulin-like growth factor 1 (IGF-1) is one of the more studied areas of known overlap between metabolism and longevity, but given the innate complexity of biology in mammals there is always some debate over the degree to which IGF-1-related mechanisms are actually determinants of life span, or even correlated with life span. Here is a study in sheep, not the usual species in investigations of the biochemistry of aging: "Longevity in livestock is a valuable trait. When productive animals live longer fewer replacement animals need to be raised. However, selection for longevity is not commonly the focus of breeding programs as direct selection for long-lived breeding stock is virtually impossible until late in the animal's reproductive life. Additionally the underlying genetic factors or genes associated with longevity are either not known, or not well understood. In humans, there is evidence that insulin-like growth factor 1 receptor (IGF1R) is involved in longevity. Polymorphism in the IGF1R gene (IGF1R) has been associated with longevity in a number of species. Recently, 3 alleles of ovine IGF1R were identified, but no analysis of the effect of IGF1R variation on sheep longevity has been reported. In this study, associations between ovine IGF1R variation, longevity and fertility were investigated [in] 1716 New Zealand sheep belonging to 6 breeds and 36 flocks. ... Ovine IGF1R C was associated with age when adjusting for flock [and] a weak negative [correlation] between fertility and longevity traits was observed."

INVESTIGATING THE ASSOCIATION OF APOE4 WITH ALZHEIMER'S
Thursday, May 17, 2012
http://www.fightaging.org/archives/2012/05/investigating-the-association-of-apoe4-with-alzheimers.php
Researchers continue to investigate why the ApoE4 gene variant is associated with Alzheimer's disease: "A well-known genetic risk factor for Alzheimer's disease triggers a cascade of signaling that ultimately results in leaky blood vessels in the brain, allowing toxic substances to pour into brain tissue in large amounts, scientists report ... a gene called ApoE4 makes people more prone to developing Alzheimer's. People who carry two copies of the gene have roughly eight to 10 times the risk of getting Alzheimer's disease than people who do not. [Scientists] found that ApoE4 works through cyclophilin A, a well-known bad actor in the cardiovascular system, causing inflammation in atherosclerosis and other conditions. The team found that cyclophilin A opens the gates to the brain assault seen in Alzheimer's. ... In the presence of ApoE4, increased cyclophilin A causes a breakdown of the cells lining the blood vessels in Alzheimer's disease in the same way it does in cardiovascular disease or abdominal aneurysm ... In studies of mice, the team found that mice carrying the ApoE4 gene had five times as much cyclophilin A compared to other mice in cells known as pericytes, which are crucial to maintaining the integrity of the blood-brain barrier. Blood vessels died, blood did not flow as completely through the brain as it did in other mice, and harmful substances like thrombin, fibrin, and hemosiderin, entered the brain tissue. When the team blocked the action of cyclophilin A, either by knocking out its gene or by using the drug cyclosporine A to inhibit it, the damage in the mice was reversed. Blood flow resumed to normal, and unhealthy leakage of toxic substances from the blood vessels into the brain was slashed by 80 percent."

ARGUING A ROLE FOR THE HYPOTHALAMUS IN AGING
Wednesday, May 16, 2012
http://www.fightaging.org/archives/2012/05/arguing-a-role-for-the-hypothalamus-in-aging.php
Researchers here analyze the proteome of the hypothalamus and argue for an important role in coordinating bodily responses to ongoing changes caused by aging: "The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. ... Based upon our rigorous analyses, we show that endogenous physiological responses to aging may be strongly orchestrated by the expression level of the GIT2 protein. The relevance of the hypothalamic expression level of this protein to the aging process in both neuronal and energy-controlling tissues reinforces the importance of this organ in the potential future development of targeted pharmacotherapeutics designed to interdict a multitude of age-related disorders."

S1P AND STIMULATION OF MUSCLE SATELLITE CELLS
Wednesday, May 16, 2012
http://www.fightaging.org/archives/2012/05/s1p-and-stimulation-of-muscle-satellite-cells.php
A possible method of boosting muscle repair, and thus treating muscle wasting conditions - such as the sarcopenia that attends aging: "a lipid signaling molecule called sphingosine-1-phosphate or 'S1P' can trigger an inflammatory response that stimulates the muscle stem cells to proliferate and assist in muscle repair. ... mdx mice, which have a disease similar to Duchenne Muscular Dystrophy, exhibit a deficiency of S1P, [and] boosting their S1P levels improves muscle regeneration ... The ability of muscles to regenerate themselves is attributed to the presence of a form of adult stem cells called 'satellite cells' that are essential for muscle repair. Normally, satellite cells lie quietly at the periphery of the muscle fiber and do not grow, move or become activated. However, after muscle injury, these stem cells 'wake up' through unclear mechanisms and fuse with the injured muscle, stimulating a complicated process that results in the rebuilding of a healthy muscle fiber. S1P is a lipid signaling molecule that controls the movement and proliferation of many human cell types. ... S1P is able to 'wake up' the stem cells at the time of injury. It involves the ability of S1P to activate S1P receptor 2, one of its five cell surface receptors, leading to downstream activation of an inflammatory pathway controlled by a transcription factor called STAT3. [This results] in changes in gene expression that cause the satellite cell to leave its 'sleeping' state and start to proliferate and assist in muscle repair. ... If these findings are also found to be true in humans with Duchenne Muscular Dystrophy, it may be possible to use similar approaches to boost S1P levels in order to improve satellite cell function and muscle regeneration in patients with the disease. Drugs that block S1P metabolism and boost S1P levels are now being tested for the treatment of other human diseases including rheumatoid arthritis. If these studies prove to be relevant in Duchenne patients, it may be possible to use the same drugs to improve muscle regeneration in these patients. Alternatively, new agents that can specifically activate S1P receptor 2 could also be beneficial in recruiting satellite cells and improving muscle regeneration in muscular dystrophy and potentially other diseases of muscle."

A POPULAR PRESS ARTICLE ON LONGEVITY SCIENCE
Tuesday, May 15, 2012
http://www.fightaging.org/archives/2012/05/a-popular-press-article-on-longevity-science.php
The media and public at large have been trained to think of medicine, and especially longevity-related medicine, in terms of pills - things you can consume, colorful drug capsules produced in the old-style fashion by Big Pharma. This is somewhat ridiculous, and leads to a focus on the entirely the wrong branches of research, those unlikely to deliver meaningful healthy life extension. The future of rejuvenation biotechnology involves gene therapies, infusions of bacterial enzymes, and so forth; for the foreseeable future little of that will be stuff that you stick into your mouth. Calling these medicines drugs rather than procedures cheapens the complexity of what is being designed and developed. Nonetheless, the oral fixation in regard to public perceptions of medicine continues, fed by the lazy press and the self-interested supplement industry. Here is an example of that sort of headlining: "But imagine if there were a drug that would slow down the aging process itself, a drug that didn't just treat a single disease but instead targeted multiple diseases of old age at once? It may sound far-fetched, but that's precisely what longevity scientists are working hard to produce. ... It's not just that we're trying to make people live longer; we're trying to make people live healthier. This is an exciting time for research. ... Indeed, top-notch research labs are rolling out studies at a rapid rate, and a growing chorus of experts believe the advances being made will ultimately lead to a crop of drugs capable of extending healthy lifespans. Signs of progress are abundant in medical journals. ... [researchers] published results showing they could markedly delay the onset of age-related diseases in mice by killing off the rodents' senescent cells. Senescent cells have stopped dividing and accumulate as organisms age. Though seemingly dormant, they're not: Just as old cars in junkyards can leak oil for years, they emit harmful substances that appear to fuel many of the diseases that strike older people. ... And it's not just senescence research that is stoking excitement. Another team of scientists [has] managed to control the aging process by targeting specialized structures at the tips of chromosomes called telomeres. ... Other scientists have found that feeding aging mice rapamycin - an immunosuppressant that's used to prevent organ rejection after transplants - can extend the lifespan of mice significantly."

METHIONINE RESTRICTION BENEFICIAL IN OLD RATS
Tuesday, May 15, 2012
http://www.fightaging.org/archives/2012/05/methionine-restriction-beneficial-in-old-rats.php
Calorie restriction extends healthy life span, and that seems to largely work through the level of methionine in the diet, though minimizing visceral fat tissue looks to be an important effect as well: "It is known that a global decrease in food ingestion (dietary restriction, DR) lowers mitochondrial ROS generation (mitROS) and oxidative stress in young immature rats. This seems to be caused by the decreased methionine ingestion of DR animals. This is interesting since isocaloric methionine restriction in the diet (MetR) also increases, like DR, rodent maximum longevity. However, it is not known if old rats maintain the capacity to lower mitROS generation and oxidative stress in response to MetR similarly to young immature animals, and whether MetR implemented at old age can reverse aging-related variations in oxidative stress. In this investigation the effects of aging and 7 weeks of MetR were investigated in liver mitochondria of Wistar rats. MetR implemented at old age decreased mitROS generation, percent free radical leak at the respiratory chain and mtDNA oxidative damage without changing oxygen consumption. Protein oxidation, lipoxidation and glycoxidation increased with age, and MetR in old rats partially or totally reversed these age-related increases. ... In conclusion, treating old rats with isocaloric short-term MetR lowers mitROS production and free radical leak and oxidative damage to mtDNA, and reverses aging-related increases in protein modification. Aged rats maintain the capacity to lower mitochondrial ROS generation and oxidative stress in response to a short-term exposure to restriction of a single dietary substance: methionine."

BMP-2 DELIVERED IN HYDROGEL TO GUIDE BONE REGROWTH
Monday, May 14, 2012
http://www.fightaging.org/archives/2012/05/bmp-2-delivered-in-hydrogel-to-guide-bone-regrowth.php
Bone morphogenetic protein 2 (BMP-2) has been used to spur healing in regenerative medicine research in past years. Here researchers are investigating its use in bone regrowth: scientists are "concentrating on the creation of new bone tissue with the aid of a biomolecule called BMP-2, which is a protein that makes bones grow. The problem with BMP-2 is that it breaks down in the body in just a few minutes. ... What's new, and what I show in my dissertation, is that by having a gel-like substance carry the protein, a so-called hydrogel, you can control both how and where the new bone is to grow ... This hydrogel can be injected and is moreover made from a type of sugar (hyaluronic acid). It occurs naturally in the body in humans and animals and is otherwise used in cosmetic products for treating wrinkles. This offers major advantages. ... On the one hand, you avoid open surgery and the risk of complications and infections that entails, and, on the other hand, there is no risk that the body will reject it. ... Applications in healthcare include both healing complicated bone fractures and growing bone tissue where there is too little or none at all. This involves defects following bone fractures and cancer or when the jawbone is too weak to support a tooth implant. Clinical testing is already underway. ... The tests show that it's working well, but the problem we need to solve is how to determine the optimal dosage of the protein. Otherwise inflammations can occur in surrounding tissue."

DIVERSITY OF REGULATORY T CELLS IN RHEUMATOID ARTHRITIS
Monday, May 14, 2012
http://www.fightaging.org/archives/2012/05/diversity-of-regulatory-t-cells-in-rheumatoid-arthritis.php
Researches make an incremental step forward in understanding the root causes of rheumatoid arthritis: "Untangling the root cause of rheumatoid arthritis has been a difficult task for immunologists, as decades of research has pointed to multiple culprits in our immune system, with contradictory lines of evidence. Now, [researchers] announce that it takes a diverse array of regulatory T cells (a specialized subset of white blood cells) to prevent the immune system from generating the tissue-specific inflammation that is a hallmark of the disease. Regulatory T cell diversity, the researchers say, provides a cumulative protective effect against rheumatoid arthritis. ... regulatory T cells (or Tregs) are a necessary component to either restrain (or encourage) the immune system's inflammatory response. Tregs are activated as molecules on their surface membranes called T cell receptors interact with 'friendly' or 'self' molecules - a way for the immune system to recognize friend from foe. Mismanagement of these Tregs, which normally serve to restrain the immune system from over-reacting to healthy tissue, could then lead to runaway inflammation. In this study, the researchers sought to examine how T cell receptors affect the ability of Tregs to suppress arthritis in a mouse that had been bred to express a 'self' molecule that drives arthritis. They showed that an array of Tregs given to the mice effectively stops arthritis. Unexpectedly, however, Tregs that are specific for the surrogate 'self' molecule do not prevent arthritis. ... We find that [a] diverse repertoire of Tregs are very effective. All of these Tregs, together, influence other components of the immune system which serves to slow down the inflammatory process that causes RA."

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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!

______________________________

CONTENT

- Maintain Yourself
- A Report from the Genetics of Aging and Longevity Conference
- Metformin, a Review
- Learning from the Regrowth of Feathers and Hair?
- Discussion
- Latest Headlines from Fight Aging!

MAINTAIN YOURSELF

A reminder that it is a good plan to put in the effort on basic health maintenance:

http://www.fightaging.org/archives/2012/05/maintain-yourself.php

"The human body needs to be taken care of in a variety of ways for best performance over the long term. Exercise, keep the weight off, try to avoid stabbing yourself. It's a considerable disadvantage that in our formative years that sort of maintenance just happens as a natural consequence of being a child - so the additional work that has to go into maintaining health as an adult comes as an unexpected chore.

"So: many of us get successful, then get fat, and then suffer age-related conditions more frequently and sooner, and then on average die younger. This isn't rocket science - most people know what they are doing to themselves, even if they aren't up to speed on the details of the biochemistry involved. But the siren song of life in a time of wealth and plenty lures you in. Maybe medical science will save you from yourself ... but I wouldn't count on it.

"So maintain yourself. You stand on the verge of a golden age in biotechnology, one that will offer unlimited healthy, youthful lifespans to those who claw their way over the threshold. Slacking on your health is turning your back on that future, it is making it harder for you to live long enough to benefit from rejuvenation biotechnologies that can be clearly envisaged today."

A REPORT FROM THE GENETICS OF AGING AND LONGEVITY CONFERENCE

Maria Konovalenko recently reported on her attendance at the Moscow conference on the genetics of aging and longevity, held last month. The post includes a great many photographs of folk from the aging research community; browse through if you are interested in putting faces to the names you read about in the science press:

http://www.fightaging.org/archives/2012/05/a-report-from-the-moscow-genetics-of-aging-and-longevity-conference.php

"It has been a while since I've posted my blog updates. The reason was the Genetics of Aging and Longevity conference. I have been involved in preparations of this meeting since December and the last month before the event was especially tough. Anyway, the conference turned out to be pretty good. I was surprised to hear so many good responses and impressions from the attendees and the speakers, so I am proud to say that the meeting was a success. The talks were superb, a lot of new and even unpublished data, a lot of discussions during the breaks and meals. I saw quite many people walking around with burning eyes - from excitement of science, of course) Some of those eyes are in the photos below. I believe this was a ground braking event on life extension topic in Russia, a truly unique gathering of minds. The more meetings like this we have, the more attention they get in the media, the better chances we have to live longer."

METFORMIN, A REVIEW

There are a few established drugs shown to modestly extend life in laboratory animals, with varying degrees of certainty. Rapamycin is probably the most concrete of those drugs at this time. Metformin is another, but the results there are far more ambiguous:

http://www.fightaging.org/archives/2012/05/metformin-a-review.php

"Metformin is a drug that shows up in discussion here every so often. It is thought to be a calorie restriction mimetic, recapitulating some of the metabolic changes caused by the practice of calorie restriction. Its effects on life span in laboratory animals are up for debate and further accumulation of evidence - the results are on balance more promising than the generally dismal situation for resveratrol, but far less evidently beneficial than rapamycin. Like rapamycin, metformin isn't something you'd want to take as though it were candy, even if the regulators stood back to make that possible, as the side effects are not pleasant and potentially serious.

"I should note as an aside that while ongoing research into the effects of old-school drugs of this nature is certainly interesting, it doesn't really present a path to significantly enhanced health and longevity. It is a pity that such research continues to receive the lion's share of funding, given that the best case outcome is an increase in our knowledge of human metabolism, not meaningful longevity therapies. Even if the completely beneficial mechanism of action is split out from the drug's actions - as seems to be underway for rapamycin - the end results will still only be a very modest slowing of aging. You could do better by exercising, or practicing calorie restriction.

"For the billions in funding poured into these drug investigation programs, there should be a better grail at the end of the road - such as that offered by the SENS vision of rejuvenation biotechnology. Targeted repair of the biological damage of aging is a far, far better strategy than gently slowing the pace of damage accumulation through old-style drug discovery programs. This is a biotechnology revolution: time to start acting like it.

Anyway, aside done, let me point you to a recent open access review on metformin: the interesting work that won't really be in any way relevant to the future of your longevity, but which I'll wager has raised more funding as an object of study than the entire present extant SENS program and directly related scientific studies. ... See what you think; it makes for an interesting read - and includes a table of results from a number of life span studies that are, indeed, all over the map. It somewhat reinforces the point that unambiguous success in extending healthy life is not going to arrive from this quarter. Think SENS, not drug discovery - what will come from the drug discovery clade is a slow, grinding, and expensive cataloging of the fine details of genetics, metabolism, and aging in mammals."

LEARNING FROM THE REGROWTH OF FEATHERS AND HAIR?

The animal kingdom is rife with species that do a far better job of regeneration than we humans. What can be learned from the details of their biochemistry?

http://www.fightaging.org/archives/2012/05/learning-from-the-regrowth-of-feathers-and-hair.php

"For some years researchers have been investigating the mechanisms of limb and organ regrowth in lower animals like salamanders, with an eye to finding out how easy or hard it would be to recreate those same capabilities in mammals - such as we humans. Do we retain the core mechanisms, lying dormant in our biochemistry, or have they been completely lost? Time and ongoing research will tell.

"But these are not the only areas of regrowth wherein researchers might learn something of interest to regenerative medicine. Consider that elk regularly regrow their antlers, for example - not a simple organ by any means. Further down the scale of impressiveness, we might consider the many higher animals that regularly regrow feathers or coats of hair. Is there anything in their biochemistry that might be discovered and adapted to cause humans to regenerate in situations where they normally do not? If you buy into the argument that salamander biochemistry is worth investigation, then it's hard to reject similar investigations in other species capable of the lesser forms of regrowth mentioned above."

DISCUSSION

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!

STILL WORKING ON AND DEBATING RESVERATROL AND SIRT1
Friday, May 11, 2012
http://www.fightaging.org/archives/2012/05/still-working-on-and-debating-resveratrol-and-sirt1.php
In recent years resveratrol has clearly fallen below the dividing line for work that is useful from a longevity perspective - if it could extend life significantly in mice, that would have been demonstrated by now. You might compare with the size of the effects on mouse lifespan for rapamycin to provide an example of a compound that is worth investigating. There is, however, a lot of money sunk into work on resveratrol and the underlying mechanisms of sirtuins, so don't expect that to halt any time soon. Research and developer institutions are prone to inertia, just like all other fields of human endeavor. In any case, here is some of the latest work on SIRT1: "If resveratrol needs SIRT1 to improve health, then animals lacking the gene should not get any benefits from the chemical. His lab published that experiment in yeast in 2003. But mice lacking SIRT1 die in the womb, or they are born with developmental defects such as blindness. To get around that problem, [researchers] engineered 'conditional knockout' mice whereby SIRT1 can be inactivated in adulthood. ... It took us two weeks to do the experiment in yeast, and five years in mouse, but finally we're there ... In normal mice, resveratrol combated the effects of a high-fat diet by boosting the efficiency of energy-generating organelles called mitochondria in skeletal muscle tissue. This effect vanished in adult mice without a working version of SIRT1. Yet SIRT1 wasn't responsible for all the beneficial effects of resveratrol ... Resveratrol stabilized the blood glucose levels of both normal and SIRT1-lacking mice on fatty diets. The chemical also improved liver health in mice without SIRT1. [The researchers also contend] that a lot the confusion over how resveratrol works comes down to dosage. At very high doses it binds other proteins besides SIRT1 ... For instance, a signalling protein called AMPK is also important to resveratrol's beneficial effects on metabolism. ... low doses of resveratrol boosted AMPK levels in various cells that expressed SIRT1, but not cells without the sirtuin. Much higher doses of resveratrol, however, activated AMPK irrespective of whether the cells expressed SIRT1."

ON THE TISSUE ENGINEERING OF TEETH
Friday, May 11, 2012
http://www.fightaging.org/archives/2012/05/on-the-tissue-engineering-of-teeth.php
Singularity Hub looks at the tissue engineering of teeth: "For years, researchers have investigated stem cells in an effort to grow teeth made for a person's own cells. Toward this end, [scientists] have developed methods to control adult stem cell growth toward generating dental tissue and 'real' replacement teeth. [The] researchers' approach is to extract stem cells from oral tissue, such as inside a tooth itself, or from bone marrow. After being harvested, the cells are mounted to a polymer scaffold in the shape of the desired tooth. The polymer is the same material used in bioreabsorable sutures, so the scaffold eventually dissolves away. Teeth can be grown separately then inserted into a patient's mouth or the stem cells can be grown within the mouth reaching a full-sized tooth within a few months. So far, teeth have been regenerated in mice and monkeys, and clinical trials with humans are underway, but whether the technology can generate teeth that are nourished by the blood and have full sensations remains to be seen. Teeth present a unique challenge for researchers because the stem cells must be stimulated to grow the right balance of hard tissue, dentin and enamel, while producing the correct size and shape."

ON ENGINEERING FUNCTIONAL CARTILAGE
Thursday, May 10, 2012
http://www.fightaging.org/archives/2012/05/on-engineering-functional-cartilage.php
An article from the Wellcome Trust: "Researchers have been engineering cartilage in the laboratory for 15 years or more, but as yet the tissues they have created don't function properly in human joints. [Researchers] are taking a new approach to try to bridge the gap between laboratory-created cartilage and the tissue our bodies make. ... Biological texts show that these lab-grown tissues have the appearance, texture, and protein and mineral components of bone and cartilage. But once they are tested in an animal, these tissues simply don't behave quite like the natural tissues they are supposed to replicate. ... Joints are remarkable feats of engineering, but efforts to grow them in the lab have focused mostly on their biology. ... Biologists attempting to create cartilage and bone over the past 15 years have typically tested the mechanical properties of their laboratory-grown tissue - for example, whether it is rubbery and resilient enough when pressure is applied. ... Just because biological tests indicate a tissue looks like bone and feels like bone, doesn't actually mean it is bone ... This is where an engineering perspective becomes important. To look at how close a match these laboratory-generated tissues really are to native bone and cartilage, [researchers] supplemented the biological analyses with engineering tests, such as bio-Raman microspectroscopy. ... You shine a laser on the material, and the way the light scatters gives you an idea of the bonds between its components. Different mineral types form different bonds, so you get a much more precise picture of what is actually present. ... If a lab-grown tissue seems from some tests to be the real thing but isn't really, then it won't behave like it once it has been implanted in a human body. ... [The researchers aim] to use an engineering approach to create a whole osteochondral interface in which bone and cartilage transition seamlessly into each other like they do in the body. ... That's the only way it will effectively transmit loads to the underlying bone. And because bone will heal, it will heal the construct into the joint."

SEEKING CONTROL OVER THYMIC INVOLUTION
Thursday, May 10, 2012
http://www.fightaging.org/archives/2012/05/seeking-control-over-thymic-involution.php
Following on from a recent post on the involution of the thymus in adults, the process by which it ceases to generate immune cells and atrophies, here is a another paper that considers some of the possible paths to interventions that maintain the thymus into old age. Given experiments in mice showing that transplant of a young thymus extends life, this seems worthy of further investigation: "The thymus is the primary organ for T-cell differentiation and maturation. Unlike other major organs, the thymus is highly dynamic, capable of undergoing multiple rounds of almost complete atrophy followed by rapid restoration. The process of thymic atrophy, or involution, results in decreased thymopoiesis and emigration of naïve T cells to the periphery. Multiple processes can trigger transient thymic involution, including bacterial and viral infection(s), aging, pregnancy and stress. Intense investigations into the mechanisms that underlie thymic involution have revealed diverse cellular and molecular mediators, with elaborate control mechanisms. This review outlines the disparate pathways through which involution can be mediated, from the transient infection-mediated pathway, tightly controlled by microRNA, to the chronic changes that occur through aging."

TOWARDS REGENERATIVE MEDICINE FOR ATHEROSCLEROSIS
Wednesday, May 9, 2012
http://www.fightaging.org/archives/2012/05/towards-regenerative-medicine-for-atherosclerosis.php
An update on the LysoSENS research project from the SENS Foundation, which aims to discover and adapt bacterial enzymes to break down the damaging buildup of unwanted metabolic byproducts in the aging body: "SENS Foundation-funded research shows that expression of a modified microbial enzyme protects human cells against 7-ketocholesterol toxicity, advancing research toward remediation of the foam cell and rejuvenation of the atherosclerotic artery. ... Atherosclerotic cardiovascular disease is the principal cause of ischaemic heart disease, cerebrovascular disease, and peripheral vascular disease, making it the root of the leading cause of morbidity and mortality worldwide. Atherosclerosis begins with the entrapment and oxidation of low-density lipoprotein (LDL) cholesterol in the arterial endothelium. As a protective response, the endothelium recruits blood monocytes into the arterial wall, which differentiate and mature into active macrophages and engulf toxic oxidized cholesterol products (oxysterols) such as 7-ketocholesterol (7-KC). Although initially protective, this response ultimately leads to atherosclerotic plaque: oxidized cholesterol products accumulate in the macrophage lysosome, and impair the processing and trafficking of native cholesterol and other materials, leading macrophages to become dysfunctional and immobilized ... more and more of these disabled "foam cells" progressively accumulate in the arterial wall, generating the fatty streaks that form the basis of the atherosclerotic lesion. Rejuvenation biotechnology can be brought to bear against this disease of aging through the identification, modification, and therapeutic delivery of novel lysosomal enzymes derived from microbes to the arterial macrophage - enzymes which are capable of degrading oxidized cholesterol products. SENS Foundation-funded researchers have been making steady progress in the identification and characterization of candidate enzymes for several years now, and a new report represents a substantial advance in the research: the rescue of cellular oxysterol toxicity by an introduced microbial lysosomal enzyme."

MORE ON NRG-1 IN NAKED MOLE-RATS
Wednesday, May 9, 2012
http://www.fightaging.org/archives/2012/05/more-on-nrg-1-in-naked-mole-rats.php
You might recall research published last near on NRG-1 levels in naked mole-rats. Here is an update: "The typical naked mole rat lives 25 to 30 years, during which it shows little decline in activity, bone health, reproductive capacity and cognitive ability. ... Naked mole rats have the highest level of a growth factor called NRG-1 in the cerebellum. Its levels are sustained throughout their life, from development through adulthood. ... NRG-1 levels were monitored in naked mole rats at different ages ranging from a day to 26 years. The other six rodent species have maximum life spans of three to 19 years. The cerebellum coordinates movements and maintains bodily equilibrium. The research team hypothesized that long-lived species would maintain higher levels of NRG-1 in this region of the brain, with simultaneous healthy activity levels. Among each of the species, the longest-lived members exhibited the highest lifelong levels of NRG-1. The naked mole rat had the most robust and enduring supply. ... In both mice and in humans, NRG-1 levels go down with age ... The strong correlation between this protective brain factor and maximum life span highlights a new focus for aging research, further supporting earlier findings that it is not the amount of oxidative damage an organism encounters that determines species life span but rather that the protective mechanisms may be more important."

CONSIDERING THE THYMUS
Tuesday, May 8, 2012
http://www.fightaging.org/archives/2012/05/considering-the-thymus.php
The thymus is the source of immune cells, but involutes in adults - it shrinks and loses its functionality. Restoring the thymus is one possible way around some of the built-in limitations of the immune system that contribute to age-related immune failure and a shorter life: "Emerging evidence indicates that the immune and metabolic interactions control several aspects of the aging process and associated chronic diseases. Among several sites of immune-metabolic interactions, thymic demise represents a particularly puzzling phenomenon because even in metabolically healthy middle-aged individuals the majority of thymic space is replaced with ectopic lipids. The new T cell specificities can only be generated in a functional thymus and, peripheral proliferation of pre-existing T cell clones provides limited immune-vigilance in the elderly. Therefore, it is hypothesized that the strategies that enhance thymic-lymphopoiesis may extend healthspan. Recent data suggest that byproducts of thymic fatty acids and lipids result in accumulation of 'lipotoxic DAMPs' (damage associated molecular patterns), which triggers the innate immune-sensing mechanism like inflammasome activation which links aging to thymic demise. The immune-metabolic interaction within the aging thymus produces a local pro-inflammatory state that directly compromises the thymic stromal microenvironment, thymic-lymphopoiesis and serves a precursor of systemic immune-dysregulation in the elderly. [This has] implications for developing future therapeutic strategies for living well beyond the expected."

ENHANCED PROTEASOME ACTIVITY IN NAKED MOLE RATS
Tuesday, May 8, 2012
http://www.fightaging.org/archives/2012/05/enhanced-proteasome-activity-in-naked-mole-rats.php
Long-lived naked mole-rats appear to have more effective housekeeping and maintenance activity in their cells: the naked mole-rat "maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. ... We found that when compared with mouse samples, naked mole-rats had significantly higher [activity]. ... the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life."

AN EXAMPLE OF THE PROLIFERATION OF STUDIES OF HUMAN LONGEVITY
Monday, May 7, 2012
http://www.fightaging.org/archives/2012/05/an-example-of-the-proliferation-of-studies-of-human-longevity.php
Extensive studies of the genetics of human longevity are growing more common - the flow of data is becoming a flood. Here is an example: "we chose to investigate 1,200 individuals of the Danish 1905 birth cohort, which have been followed since 1998 when the members were 92-93 years old. The genetic contribution to human longevity has been estimated to be most profound during the late part of life, thus these oldest-old individuals are excellent for investigating such effect. The follow-up survival data enabled performance of longitudinal analysis, which is quite unique in the field of genetic epidemiology of human longevity. ... However, this study explores the genetic contribution to survival during the ninth decade of life, hence, in order to investigate the genetic contribution to survival in younger elderly we also included 800 individuals of the Study of Middle-aged Danish twins (MADT). ... The analyses of the data set verified the association [with longevity of] SNPs in the APOE, CETP and IL6 genes, [and] pointed to new candidate genes of human longevity: especially SNPs in the INS, RAD52 and NTHL1 genes appeared promising. As part of these investigations, replication studies of the single-SNP level findings were conducted in German case-control samples of 1,613 oldest-old (ages 95-110) and 1,104 middle-aged individuals and in a Dutch prospective cohort of 563 oldest-old (age 85+). ... Interesting aspects of the study were that the majority of the rare alleles of the identified SNPs were longevity variants, not mortality variants, indicating that at least in our study population, longevity is primarily affected by positively acting minor alleles. ... Furthermore, the genotype data generated were used for a number of replication studies on variation in the FOXO3A, TERT and TERC genes. These studies were performed in response to new data being published on the association of genetic variation in the genes with longevity (FOXO3A and TERT) and with telomere length (TERT and TERC). Our studies verified a role of TERC in human telomere length and of FOXO3A in human longevity (survival from middle age to old age), while a novel role of TERC in human longevity was found."

A LOOK AT TISSUE ENGINEERING OF NOSES AND EARS
Monday, May 7, 2012
http://www.fightaging.org/archives/2012/05/a-look-at-tissue-engineering-of-noses-and-ears.php
Tissue engineering is steadily advancing into the easier areas of growing replacement parts: "Other groups have tried to tackle nose replacement with implants but we've found they don't last. They migrate, the shape of the nose changes. But our one will hold itself completely, as it's an entire nose shape made out of polymer. ... Inside this nanomaterial are thousands of small holes. Tissue grows into these and becomes part of it. It becomes the same as a nose and will even feel like one. ... When the nose is transferred to the patient, it doesn't go directly onto the face but will be placed inside a balloon inserted beneath the skin on their arm. After four weeks, during which time skin and blood vessels can grow, the nose can be monitored, then it can be transplanted to the face. At the cutting edge of modern medicine, [researchers] are focusing on growing replacement organs and body parts to order using a patient's own cells. There would be no more waiting for donors or complex reconstruction - just a quick swap. And because the organ is made from the patient's own cells, the risk of rejection should, in theory, be eliminated. ... We seed the patient's own cells on to the polymer inside a bioreactor. ... This is a sterile environment mirroring the human body's temperature, blood and oxygen supply. ... As the cells take hold and multiply, so the polymer becomes coated. The same methods could be applied to all parts of the face to reconstruct those of people who have had severe facial traumas."

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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!

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CONTENT

- Video: "this house wants to defeat aging entirely"
- Radical Life Extension at the Melbourne Humanity+ Conference
- Plausible, Possible, Expensive, Prohibited
- Cryonics Magazine, March-April 2012
- Discussion
- Latest Headlines from Fight Aging!

VIDEO: "THIS HOUSE WANTS TO DEFEAT AGING ENTIRELY"

Video has been posted of the recent Oxford University Science Society public debate between Aubrey de Grey of the SENS Foundation and Colin Blakemore, former head of the Medical Research Council.

http://www.fightaging.org/archives/2012/04/video-this-house-wants-to-defeat-ageing-entirely.php

"Formal debates in science and medicine, sponsored by academic societies, are a long-standing tradition in England: in the history of the sciences many of the important inflection points and transitions between eras of knowledge were marked by public debates held between the worthies of the time. The debates do not in and of themselves determine anything: they are a reflection of ongoing matters of interest and the clash of strategies or theories that currently engage the scientific community. Thus it should be taken as a promising sign that awareness of SENS-style rejuvenation biotechnology is at a level at which such debates are held and well-attended.

"Rejuvenation through medical technology is in our future, and factions within the scientific and medical development communities are forming and polarizing around opinions on plausibility, how to construct therapies for aging, and just how urgent it is to take action on this issue. Much of the ongoing debate within the scientific community is invisible to the world at large - but make no mistake, it is taking place, and has been for the better part of a decade. When it comes to aging and what to do about it, the research community of today is a radically different place from the research community of the first years of this century."

RADICAL LIFE EXTENSION AT THE HUMANITY+ MELBOURNE CONFERENCE

And here is Aubrey de Grey in the news again, getting good press in Australia on the occasion of the 2012 Humanity+ conference in Melbourne held this past weekend:

http://www.fightaging.org/archives/2012/05/radical-life-extension-at-the-melbourne-humanity-conference.php

"When British gerontologist Aubrey de Grey talks about radical life extension for humans - decades, even centuries more of existence - he is not imagining us slogging by with brain plaque, loose dentures and walking frames. Rather, we would be in rude health, with all the hallmarks of age in abeyance, even retreat. No wrinkles, fraying organs, leaky bladders or aching joints. And not much need for aged care or pensions. ... In a world where life expectancy has already dramatically increased over the past century or two, we now face the likelihood of being able to custom-order fresh organs and body parts on 3D-printers, and to treating the basic causes of ageing with the likes of stem-cell therapy and nanotechnology.

"De Grey and [Natasha] Vita-More, in Melbourne for this weekend's Humanity+ conference, are in the vanguard of futurists who believe that looking great or designing our bodies to suit (blue skin and magenta eyes anyone?) will be fringe benefits. That is because, in a fast-approaching era of living longer, healthier lives, it is expected we will have time to enjoy the wisdom and opportunities of getting older - we won't be so focused on all the medical appointments, decrepitude and fragility associated with old age. ... de Grey, who once said some of today's infants might live to 1000 years old, and who not so long ago was viewed sceptically by other scientists for his insistence that ageing is a preventable, treatable medical condition, now sees much broader acceptance of his ideas among scientists.

'"'Attitudes have changed enormously,' he says. 'The feasibility of what I have been proposing is now generally accepted. It took a long time, because essentially ... people who were expert in regenerative medicine didn't know about ageing; and people expert in ageing didn't know about regenerative medicine.'

"A bigger battle has been with the attitudes of the general population, who view ageing as natural and inevitable and who, asked if they would like to have much longer lifespans, deliver predictable objections, often saying they would get bored (so much for the human imagination). De Grey says these responses are because people don't think of ageing in the same category as other diseases: if they understood they could live much longer without medical problems or signs of ageing, they would be enthusiastic. 'They just don't think of [ageing] as a plausible target for medicine.'"

PLAUSIBLE, POSSIBLE, EXPENSIVE, PROHIBITED

What could you choose to do today, if you had enough money for a major medical procedure, and the legion of medical regulators didn't exist? If you were free to choose your own risks in medicine, and doctors and researchers were free to be paid to help you? Here are a few examples, with varying degrees of risk, reward, and unknown factors:

http://www.fightaging.org/archives/2012/05/plausible-possible-expensive-prohibited.php

"Have your aging immune system wiped out with chemotherapy and replaced from your stem cells. Your wager here would be that undergoing chemotherapy (not a wonderful experience under the best of circumstances) will cause you less harm in the long term than keeping your original, increasingly misconfigured immune system. Alternately, you could wait a decade for targeted cell-killer therapies demonstrated in mice to become a practical concern in humans.

"Undergo any one of a number of potential enhancing gene therapies. For example, why not pay your way into possessing a myostatin mutation? That boosts muscle mass, increases resistance to a range of age-related conditions, and otherwise seems to be beneficial all-round in mammals.

"Purchase stem cell infusions of the sort that seem to be at least modestly helpful for any number of degenerative conditions - a better option than traditional pharmaceutical medicines. But of course you can't do that in the US, just like you can't benefit from near all of the most recent advances, locked away in trials for years yet. You'd have to head overseas as a medical tourist to become a customer of the more reliable clinics in Asia or the Middle East.

"Decide in your healthy old age that the possible benefits outweigh the risks for infusion-based biphosphonate therapy [which was unexpectedly shown to extend life expectancy by years in the elderly]. Of course you can't obtain that legally as a healthy person - those regulators again, deciding that they know better and anyone who disagrees with them will ultimately wind up in jail.

"Choose to end your own long-lived life in a safe and painless way at the time of your choosing, while attended by cryonics professionals who can provide an immediate and expert preservation - offering absolutely the best chance of later restoration with minimal damage, while keeping the cost to a sensible minimum thanks to scheduling.

"I could go on - that just scratches the surface. But of course any group that gathered in the US to try these things, or offer services, or make the process as safe and transparent as possible would quickly find themselves prosecuted and jailed. The land of the free long ago ceased to have much to do with liberty or personal freedom. Freedom is the freedom to take your own risks and pay the costs if you pull a bad card from the deck - and that freedom is exactly what drives progress. Take it away and what results is the regulatory stagnation you see in medicine today."

CRYONICS MAGAZINE, MARCH-APRIL 2012

The March-April issue of Cryonics is available online:

http://www.fightaging.org/archives/2012/05/cryonics-magazine-march-april-2012.php

"The main topic of the issue ties into the ongoing discussion on maintaining Alcor's reserve of funds at a sufficient level for the long term - which is essentially a battle against the predatory inflation produced by the self-serving actions of politicians and political appointees. The political class can be expected to create ever more money from nothing, continually reducing the value of money in circulation and savings accounts, because it is the most effective way to tax the masses - all other forms of taxation generate far more unrest, resistance, and non-compliance, and are thus much more self-limiting in the revenue they can generate.The battle against the inflation resulting from depreciation of the currency is fought by all entities that must tie contracts inked today to outlays required years from now:

"As evidenced by recent exchanges on the Alcor Member Forums, our members have a wide variety of suggestions for how to close the substantial funding gap that has been produced by Alcor's practice to date of not raising cryopreservation minimums for existing members. If there is one area of strong agreement, however, it is that all members who are underfunded for today's cryopreservation minimums and who can afford to change or upgrade their life insurance, should do so. This will not just reduce Alcor's funding shortfall but it will also allow the member to secure new cryopreservation and storage technologies that cannot be offered without charging an additional amount. Surplus funding can also be allocated to a personal revival trust or to Alcor's hardship fund to help members with poor funding and/or challenges to pay annual dues.

"The March-April issue of Cryonics magazine features an extensive review of life insurance options by Alcor member and life insurance agent Rudi Hoffman. Rudi introduces the topic by presenting the disturbing long-term effects of (medical) inflation. Not all of Alcor's services may be subject to the kind of cost increases we see in medicine but it is prudent to plan using conservative assumptions. After this sobering introduction, Rudi runs us through the various forms of life insurance, their pros and cons, and how to read those long, intimidating policy illustrations. We at Alcor hope that many of you will make efforts to update your cryonics funding to make it easier to solve the underfunding problem and to assist with the really hard cases."

DISCUSSION

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!

MAKING OLD STEM CELLS FUNCTIONALLY YOUNG
Friday, May 4, 2012
http://www.fightaging.org/archives/2012/05/making-old-stem-cells-functionally-young.php
More rejuvenation of stem cell function demonstrated in mice: "Researchers have rejuvenated aged hematopoietic stem cells to be functionally younger, offering intriguing clues into how medicine might one day fend off some ailments of old age. ... The paper brings new perspective to what has been a life science controversy - countering what used to be broad consensus that the aging of hematopoietic stem cells (HSCs) was locked in by nature and not reversible by therapeutic intervention. HSCs are stem cells that originate in the bone marrow and generate all of the body's red and white blood cells and platelets. They are an essential support mechanism of blood cells and the immune system. As humans and other species age, HSCs become more numerous but less effective at regenerating blood cells and immune cells. ... Researchers in the current study determined a protein that regulates cell signaling - Cdc42 - also controls a molecular process that causes HSCs from mice to age. Pharmacologic inhibition of Cdc42 reversed HSC aging and restored function similar to that of younger stem cells. ... We know the aging of HSCs reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia, and may be the cause of tissue attrition in certain systems of the body. ... One reason the research team focused on Cdc42 is that previous studies have reported elevated activity of the protein in various tissue types of older mice - which have a natural life span of around two years. Also, elevated expression of Cdc42 has been found in immune system white blood cells in older humans. In the current study, researchers found elevated activity of Cdc42 in the HSCs of older mice. They also were able to induce premature aging of HSCs in mice by genetically increasing Cdc42 activity in the cells. ... To test the rejuvenated cells, the researchers used a process known as serial competitive transplantation. This included extracting HSCs from young (2-4 months) and aged (20-26 months) mice and processing them in laboratory cultures. Young and rejuvenated cells were then engrafted into recipient mice. This allowed scientists to compare how well young and rejuvenated aged HSCs started to repopulate and transform into different types of blood cells. It also confirmed that HSCs rejuvenated by targeting Cdc42 do function similarly to young stem cells."

SELF-ASSEMBLING NANOPARTICLES TO TARGET UNWANTED CELLS
Friday, May 4, 2012
http://www.fightaging.org/archives/2012/05/self-assembling-nanoparticles-to-target-unwanted-cells.php
An example of ongoing work to make targeted cell-killing technologies economically practical: "For more than a decade, researchers have been trying to develop nanoparticles that would deliver drugs more effectively and safely. The idea is that a nanoparticle containing a drug compound could selectively target tumor cells or otherwise diseased cells, and avoid healthy ones. Antibodies or other molecules can be attached to the nanoparticle and used to precisely identify target cells. ... [Researchers] devised a method by which the building blocks of the nanoparticle and the drug self-assemble into a final product. Two types of polymer combine to form the tangled mesh of [a] drug-laden spherical nanoparticle. One of these polymers has two chemically and structurally distinct regions, or 'blocks': a water-insoluble block that forms part of the mesh that encapsulates the drug, and a water-soluble block that gives the final product a stealthy corona to evade the immune system. The other type of polymer has three blocks: the same two as the first, as well as a third region that contains a targeting molecule - the signal that will ensure the final particles attach to the desired cell types. The drug-carrying nanoparticles are formed by simply mixing these polymers together with the drug in the appropriate conditions. The self-assembling polymers can be produced in a repeatable and scalable fashion. But the method has an additional benefit ... The method by which the nanoparticles are built - from individual preparations of the two-block and three-block polymers - would also let researchers use high-throughput screening approaches, akin to how medicinal chemists design and test new drug compounds. Each block could be tweaked - extend one block, change the charge on another - and the relative amounts of each polymer could be varied. With so many parameters for tinkering, [scientists] can screen many combinations."

REPLACING DAMAGED DJ-1 IN PARKINSON'S DISEASE
Thursday, May 3, 2012
http://www.fightaging.org/archives/2012/05/replacing-damaged-dj-1-in-parkinsons-disease.php
It has been a number of years since researchers started to investigate the role of DJ-1 in Parkinson's disease. Here, the work has made it to the stage of a possible therapy: "As we age, we naturally lose dopamine-producing neurons. Parkinson's patients experience a rapid loss of these neurons from the onset of the disease, leading to much more drastic deficiencies in dopamine than the average person. ... Mutations in the gene known as DJ-1 lead to accelerated loss of dopaminergic neurons and result in the onset of Parkinson's symptoms at a young age. The ability to modify the activity of DJ-1 could change the progress of the disease. [Researchers have] now developed a peptide which mimics DJ-1's normal function, thereby protecting dopamine- producing neurons. What's more, the peptide can be easily delivered by daily injections or absorbed into the skin through an adhesive patch. Based on a short protein derived from DJ-1 itself, the peptide has been shown to freeze neurodegeneration in its tracks, reducing problems with mobility and leading to greater protection of neurons and higher dopamine levels in the brain. ... We attached the DJ-1-related peptide to another peptide that would allow it to enter the cells, and be carried to the brain. ... In pre-clinical trials, the treatment was tested on mice ... From both a behavioral and biochemical standpoint, the mice that received the peptide treatment showed remarkable improvement. Symptoms such as mobility dysfunctions were reduced significantly, and researchers noted the preservation of dopamine-producing neurons and higher dopamine levels in the brain. Preliminary tests indicate that the peptide is a viable treatment option. Though many peptides have a short life span and degrade quickly, this peptide does not."

THE POWER OF MODERATE EXERCISE
Thursday, May 3, 2012
http://www.fightaging.org/archives/2012/05/the-power-of-moderate-exercise.php
Moderate exercise improves life expectancy: "Undertaking regular jogging increases the life expectancy of men by 6.2 years and women by 5.6 years, reveals the latest data from the Copenhagen City Heart study ... the study's most recent analysis (unpublished) shows that between one and two-and-a-half hours of jogging per week at a 'slow or average' pace delivers optimum benefits for longevity. ... SThe study, which started 1976, is a prospective cardiovascular population study of around 20,000 men and women aged between 20 to 93 years. The study, which made use of the Copenhagen Population Register, set out to increase knowledge about prevention of cardiovascular disease and stroke. Since then the study, which has resulted in publication of over 750 papers, has expanded to include other diseases ... The investigators have explored the associations for longevity with different forms of exercise and other factors. For the jogging sub study, the mortality of 1,116 male joggers and 762 female joggers was compared to the non joggers in the main study population. All participants were asked to answer questions about the amount of time they spent jogging each week, and to rate their own perceptions of pace (defined as slow, average, and fast). ... The first data was collected between 1976 to 1978, the second from 1981 to 1983, the third from 1991 to 1994, and the fourth from 2001 to 2003. For the analysis participants from all the different data collections were followed using a unique personal identification number in the Danish Central Person Register. ... These numbers have been key to the success of the study since they've allowed us to trace participants wherever they go. ... Results show that in the follow-up period involving a maximum of 35 years, [risk] of death was reduced by 44%."

MORE EVIDENCE TO SHOW THAT EXCESS FAT CAUSES CHRONIC INFLAMMATION
Wednesday, May 2, 2012
http://www.fightaging.org/archives/2012/05/more-evidence-to-show-that-excess-fat-causes-chronic-inflammation.php
Chronic inflammation is a bad thing - it greatly increases your risk of suffering age-related disease, and may be one of the more important mechanisms linking excess fat tissue to risk of disease and lowered life expectancy. Here is more evidence to show that being overweight exposes a person to greater inflammation: "Postmenopausal women who were overweight or obese and lost at least 5 percent of their body weight had a measurable reduction in markers of inflammation. ... Both obesity and inflammation have been shown to be related to several types of cancer, and this study shows that if you reduce weight, you can reduce inflammation as well. ... Women in the trial who were assigned to a weight loss intervention had a goal of 10 percent weight reduction during the course of one year achieved through a diet intervention with or without aerobic exercise. ... The researchers measured levels of C-reactive protein, serum amyloid A, interleukin-6, leukocyte and neutrophil in 439 women. At the end of one year, C-reactive protein reduced by 36.1 percent in the diet-alone group and by 41.7 percent in the diet and exercise group. Interleukin-6 decreased by 23.1 percent in the diet group and 24.3 percent in the diet and exercise group. ... there were greater reductions in these measures among women who lost at least 5 percent of their body weight. They also found that exercise alone, without a dietary weight loss component, had little effect on inflammation markers."

TELOMERES IN DISEASE AND AGING
Wednesday, May 2, 2012
http://www.fightaging.org/archives/2012/05/telomeres-in-disease-and-aging.php
An introduction to what is known of telomeres can be found at the Scientist: "The ends of linear chromosomes have attracted serious scientific study - and Nobel Prizes - since the early 20th century. Called telomeres, these ends serve to protect the coding DNA of the genome. When a cell's telomeres shorten to critical lengths, the cell senesces. Thus, telomeres dictate a cell's life span - unless something goes wrong. Work over the past several decades has revealed an active, though limited, mechanism for the normal enzymatic repair of telomere loss in certain proliferative cells. ... Telomeres shorten as we age. By analogy to the cellular mitotic clock, telomeres have been postulated as a marker of 'genetic age,' and telomere length has been marketed as a simple predictor of longevity. Assays of telomere length have been bundled with recommendations for lifestyle modification and for drug therapy, neither based on appropriate clinical studies. Simple but appealing arguments relating telomeres and aging are currently controversial, likely simplistic, and potentially harmful. Telomere length does indeed reflect a cell's past proliferative history and future propensity for apoptosis, senescence, and transformation. Cellular aging, however, is not equivalent to organ or organismal aging. ... Studies in humans have attempted to relate telomere length to life span. In the provocative initial publication from the University of Utah in 2003, individuals around 60 years of age who had the longest telomeres lived longer than did subjects with the shortest telomeres, but the main cause of death in the latter group was, inexplicably, infectious disease; the persons with shorter telomeres did not have a higher rate of cancer deaths. Moreover, these findings have not been confirmed in other studies of older subjects. In another study evaluating a different population, telomere length failed to predict survival, but interestingly it correlated with years of healthy life. In a Danish study of people aged 73 to 101 years, telomeres correlated with life expectancy in a simple univariate analysis, but only before the researchers corrected for age, suggesting that the correlation was driven simply by the fact that younger subjects had longer telomeres. And a Dutch study of 78-year-old men found that while telomere lengths eroded with age, they failed to correlate with mortality."

MICHAEL BATIN'S SPEECH AT THE 2ND INTERNATIONAL CONFERENCE ON THE GENETICS OF AGING AND LONGEVITY
Tuesday, May 1, 2012
http://www.fightaging.org/archives/2012/05/michael-batins-speech-at-the-2nd-international-conference-on-the-genetics-of-aging-and-longevity.php
Following on from a recent interview with Michael Batin, one of the organizers of the 2nd International Conference on the Genetics of Aging and Longevity, here is a machine translation of his speech to the attendees: "We hope that the conference will identify the most promising points of growth, will contribute to international scientific and research funding [from] international and national foundations, private investors. Let me ask the main question [in biogerontology]. Why [is] aging research funded by the minimum amount? How to change the situation? How to change the attitudes of society and government to seek scientific methods of prolonging life? The first thing that prevents us [is that] aging itself is not considered a disease. Although the aging process fully complies with all common signs of the disease. Aging - a cause of illness and disease. Failure to understand this - [a] deadly mistake. The price of this confusion is very real - [100,000] people die every day from diseases related to aging. Another misconception - aging can be successful and healthy. No, [it] can not! Aging can flow more smoothly. Aging can be slowed down. But you can not make a destructive process or healthy, or successful. As it is impossible to make a decent poverty [or toothache enjoyable]. [This is] the amazing paradox. Nobody disputes the fact that there is nothing more important than human life. All agree that there is nothing more terrible than death. Many suspect that the main cause of death in people [is] aging. But few people make this a logical conclusion. What is the most useful and meaningful activity that has ever engaged [mankind? It is the] struggle with aging. And in particular [the study of] fundamental mechanisms of aging and genetics of longevity. That's what [the scientists in this room do].. And I believe [that they are the] most helpful people on the planet."

MAINTENANCE OR RESERVE IN THE AGING BRAIN?
Tuesday, May 1, 2012
http://www.fightaging.org/archives/2012/05/maintenance-or-reserve-in-the-aging-brain.php
There are numerous high-level hypotheses that seek to explain why different people suffer neurodegeneration to different levels. Some people remain sharp in old age, whilst others descend into dementia. At the fine-grained level of measuring different types of mental capacity, there are also large variations across an aging population: "Episodic memory and working memory decline with advancing age. Nevertheless, large-scale population-based studies document well-preserved memory functioning in some older individuals. The influential 'reserve' notion holds that individual differences in brain characteristics or in the manner people process tasks allow some individuals to cope better than others with brain pathology and hence show preserved memory performance. Here, we discuss a complementary concept, that of brain maintenance (or relative lack of brain pathology), and argue that it constitutes the primary determinant of successful memory aging. We discuss evidence for brain maintenance at different levels: cellular, neurochemical, gray- and white-matter integrity, and systems-level activation patterns. Various genetic and lifestyle factors support brain maintenance in aging and interventions may be designed to promote maintenance of brain structure and function in late life." It makes more sense for neurodegeneration to be more greatly affected by the impact of regular exercise on long-term tissue health than by the genetics of having a cognitive research.

AN INTERVIEW ON AGING AND DEMENTIA
Monday, April 30, 2012
http://www.fightaging.org/archives/2012/04/an-interview-on-aging-and-dementia.php
An interview with a researcher in the field: "the reality is that our brains age throughout life and, in fact, the science tells us that at age 45 we can measure cognitive and memory decline in the average person. There's a steady gradual decline that continues. ... Age is the greatest risk factor. By age 65 or older, your risk is about 10 per cent for Alzheimer's dementia. By 85, it's 40 per cent or more. The implications are that we have a lot more people who have dementia and a lot more people concerned about developing it. ... The studies of successful aging tell us that, when it comes to cognitive success or avoiding dementia or developing it, for the average person only a third of what determines that cognitive outcome results from genetics, from what we inherit. Rarely there are families, less than 2 per cent of cases, with very strong genetic components; they have mutations that cause the disease very early in life. For the vast majority, the genetics are not as strong. They are a factor. About 20 per cent of the population has this risk. It increases the likelihood of getting the disease and the likelihood of getting it at an earlier age but it's not 100 per cent. That means that two-thirds of the formula comes from non-genetic factors: the lifestyle choices we make every day have a major impact on how well our brains age. ... Physical exercise, mental exercise, nutrition, stress management and other behaviours, like avoiding head trauma, not smoking and so forth. ... Exercise seems obvious [but] it may not be completely obvious for people. They know there is a connection between exercise and physical health, exercise and avoiding heart disease. But not everybody is aware of the strong connection between physical exercise and brain health."

SPAWNING DESIGNER LYMPH NODES
Monday, April 30, 2012
http://www.fightaging.org/archives/2012/04/spawning-designer-lymph-nodes.php
Researchers are trying to create new lymph nodes in the body, but tailored to specific needs: "Designer lymph nodes are built with specialized gene-modified cells that are injected into patients and produce a pre-planned immunologic response for cancer patients locally and then throughout their bodies. The researchers are examining a cancer vaccine 'boosting' effect of the manufactured lymph nodes in patients with advanced melanoma. ... Patients with cancer have a dysfunctional immune system either because of the tumor's presence in the body or as a side effect of drugs or radiation used to treat the tumor. The designer lymph nodes, aimed at rebuilding their immune systems, may overcome this dysfunction. ... the researchers are using antigen-presenting cells made from the patient's blood, which are then genetically manipulated to express certain genes before injection into patients. They can inject gene-modified cells at multiple, independent sites throughout the body to create independent lymph nodes that work together. In the trial, the researchers have found early formation of lymph nodes at the vaccine injection sites and are subsequently testing the nature and anti-tumor function of them. [The team] anticipate partnering with [other institutions] to create designer lymph nodes for diseases other than cancer and expand their designer gene immunity boosting research into fighting infectious diseases and even improving the function of immune systems in the elderly."

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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!

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CONTENT

- An Interview with Michael Batin
- Conflating Aging and Degeneration
- The FDA is a Destructive Force
- Discussion
- Latest Headlines from Fight Aging!

AN INTERVIEW WITH MICHAEL BATIN

The 2nd International Conference on the Genetics of Aging and Longevity was held this past week in Moscow, well-attended by the aging research community. Here is an interview, machine translated from Russian:

http://www.fightaging.org/archives/2012/04/an-interview-with-michael-batin.php

"Earlier this month, the Moscow News ran an interview with Michael Batin, one of the [conference] organizers. His views are representative of the Russian community, whose members tend to be forthright and direct when it comes to the end goals of longevity science: to defeat aging entirely, banish the suffering it causes, and usher in an era of ageless humans. More power to them - we could do with a lot more of that sort of outspoken advocacy here in the Anglosphere.

"Q: What is the real goal that we set ourselves right now? Can you say, talk about extending the life of ten years from now?

MB: In ten years? It is not even present, and yesterday. It has long been proven that reducing caloric intake [and even] just a healthy lifestyle [lead to a longer life]. Our goal is different - a victory over an aging, it is by and large the whole purpose of medical science. After all, if you think about all of the doctors [dedicated to the] prolongation of life, the estrangement of death. A person does not want to die right now, well, anti-aging does not differ fundamentally, it is also the struggle with death.

Q: So you're talking about immortality?

MB: Yes. This is the ultimate goal. In the coming ten years, you can raise the life expectancy [to] 150 years, with adequate [resources and large enough research community]. If, for example, to do research megaproject like the American lunar program. And if we know in ten years that will live more than a hundred years, this will give us more time to find a way to further extend [life].

Q: But how? Are there any pills?

MB: If you're talking about a miracle pill, then, of course not. Aging depends on many factors, and is now the main problem is just that we do not know them all. And the proposed mega-project just involves a systematic search for the causes of aging.

Q: And it's all in the mega-project? [It's] going to cost [a] quite impossibly high sum.

MB: But now we are spending huge amounts of money on arms - you've seen defense spending in Russia? - And do not invest in [biogerontology], fundamental research on the causes of aging. Even in the U.S., [where] gerontology takes a billion dollars, [that is] their total spending, of that billion is spent on Alzheimer's disease, [on] geriatrics, and [only a small fraction of it on] the fundamental work on finding the root causes of aging."

CONFLATING AGING AND DEGENERATION

Aging absent degeneration would be a wonderful thing:

http://www.fightaging.org/archives/2012/04/conflating-aging-and-degeneration.php

"There's a lot to be said for aging. The passage of years offers many opportunities to master favored skills, figure out solutions to the issues and upsets of youth, earn the resources and connections needed for true self-sufficiency and confidence, and much more. You can build a great life, given just the time to work on it and a modicum of common sense - and then keep on building atop the foundation of that great life. Humans age like distillates: it can just keep getting better. But of course there is the matter of degeneration and death, of disease and decrepitude. The fact that older people are generally happier, more secure, and more confident despite what happens to the body with age is a testament to just how good being aged is. That the majority evaluate their position as far superior to that of earlier years despite the increasing corrosion of the body and the ticking away of time remaining is a powerful statement.

"On this topic, I should note that over the years an unfortunately large number of apologists for aging have become somewhat dazzled by the good parts of the package, to the point at which they are unwilling to talk about picking apart aging and degeneration, or trying to radically change aging through medical technology. To their view, the world is what it is, and we should just focus on the positives and suffer the negatives with dignity. Not that that last point is easy at all - there is no dignity in the failing of the body and mind, only horrors that the dominant voices of this society seem to have chosen to try to close away behind the curtains.

"It is both somewhat strange and somewhat understandable to find so many conservatives - in the dictionary definition of the word, not the political definition - in an age of rampant, ongoing, omnipresent change. Those who benefit the most from technological progress, and consequent decade by decade shifts in the minutiae of the human condition, nonetheless adopt positions based on the idea that what presently exists will continue to exist as-is into the future. It's denial, it's letting the ape inside drive - the ape who really, really, doesn't like change or upsets to the present carefully constructed social hierarchy, no matter how beneficial it might be.

"Being aged is great, but it's just plain dumb to try to turn that into an argument that being sick, lessened, in agony, and driven mad is also great. Medicine will be able to remove all of these ugly aspects of old age, provided that we work hard enough and fund the right sort of research and development to a sufficient degree. The people who paint on sunny smiles and say that nothing will ever change are only helping to hold back that future."

THE FDA IS A DESTRUCTIVE FORCE

We would be so much further along in applied biotechnology if not for the perverse engines of regulation that hold back progress in much of the world:

http://www.fightaging.org/archives/2012/04/the-fda-is-a-destructive-force.php

"The employees and appointees of the US Food and Drug Administration have caused an incredible destruction of value and progress over the time that the agency has existed. Their regulatory policies become ever more onerous with each passing year, as unaccountable bureaucrats follow their incentives: nothing good can happen to their careers as a result of approving new technologies, and nothing bad tends to happen to their careers as a result of making it really, really hard to bring new medicine to the clinic. So of course you wind up with an organization whose members collectively pay nothing more than lip service to their declared mission, while working to make sure that medicine stays moribund in a slow-motion stasis. This is most evident in the cancer research community, largely because of its size, but it applies just as evenly across all forms of medicine:

"A 2010 study in the Journal of Clinical Oncology by researchers from the M.D. Anderson Cancer Center in Houston, Texas found that the time from drug discovery to marketing increased from eight years in 1960 to 12 to 15 years in 2010. Five years of this increase results from new regulations boosting the lengths and costs of clinical trials. The regulators aim to prevent cancer patients from dying from toxic new drugs. However, the cancer researchers calculate that the delays caused by requirements for lengthier trials have instead resulted in the loss of 300,000 patient life-years while saving only 16 life-years.

"To add to this picture, you must also see incumbent Big Pharma entities and their executives and lobbyists - a deeply enmeshed network of regulatory capture. They are far more willing to use the current system as a weapon to suppress disruptive innovation in their industry than to be a source of innovation themselves. So it goes, just as in any other heavily regulated market. The strategic goals of the major players wind up having very little to do with creating beneficial change, and everything to do with keeping things the same as they are now.

"Though the United States urgently needs new treatments for common illnesses such as heart disease, stroke, and diabetes, the nation's system for drug approval discourages innovation and investment, especially for our most pressing public health challenges. In this paper, we find that the main culprit is the high cost of Phase III clinical trials, which are required for FDA approval of most drugs. We examined drug development in four major public health areas and discovered that for any given drug on the market, typically 90 percent or more of that drug's development costs are incurred in Phase III trials. These costs have skyrocketed in recent years, exacerbating an already serious problem."

DISCUSSION

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!

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LATEST HEADLINES FROM FIGHT AGING!

RESEARCHER STEVEN AUSTAD WRITES A BIWEEKLY COLUMN ON AGING SCIENCE
Friday, April 27, 2012
http://www.fightaging.org/archives/2012/04/researcher-steven-austad-writes-a-biweekly-column-on-aging-science.php
This seems like an interesting marker of public awareness of aging science; one of the noted researchers in the field recently started on a biweekly column for a local paper. Links to the columns published to date can be found on this page: "In my last column I discussed something we all know intuitively: Generally speaking, larger species of animals live longer than smaller species and this pattern extends even to whales that live more than 200 years. Are there dramatic exceptions to this rule - like people, for instance? Think of other mammals about our size, such as deer or mountain lions or seals. Don't we live longer than they do? The answer is, 'Yes, we do.' Humans live about five times as long as the average mammal of the same size, which makes us pretty special - but not as special as bats. Texas is bat country, as anyone who has watched millions of bats boil out of Bracken Cave or from under Austin's Congress Avenue Bridge can verify. What many people don't realize is how long bats live. For their size, bats are the longest-lived mammals by far, living up to 10 times as long as an average mammal of similar size. ... Think about this for a second. Your dog or cat, eating the best food science can provide, protected from predators and the elements and vaccinated against all sorts of diseases, is doing well to reach 15 to 20 years of age. By comparison, in order for a bat in the wild to survive it must catch its own prey, elude predators, resist climatic extremes, and avoid a wide range of infectious diseases. Yet despite these challenges, bats can live twice as long as your pampered pet." Current thinking on bat longevity looks to be similar to theories on naked mole rat longevity - it has to do with resistance of cell membranes (and especially mitochondria) to oxidative damage, otherwise known as the membrane pacemaker hypothesis of aging. This is thought to have developed in bats, and in birds, in respond to the metabolic demands of flight.

EXAMINING MITOCHONDRIAL DNA DAMAGE IN DETAIL
Friday, April 27, 2012
http://www.fightaging.org/archives/2012/04/examining-mitochondrial-dna-damage-in-detail.php
Damage to mitochondrial DNA contributes to aging, and mitochondrial function is in general influential upon aging - damage causes harm by preventing the production of protein machinery vital to mitochondrial activity, which is the start of a long process that sees cells overtaken by dysfunctional mitochondria, and exporting their dysfunction to surrounding tissue by emitting harmful reactive molecules. There are numerous different sorts of DNA damage, however. Point mutations, for example, have been shown to do little to aging. Deletions, where whole reaches of DNA are knocked out, are a different story, and here researchers are investigating how this form of DNA damage varies between species: "Deletion mutations within mitochondrial DNA (mtDNA) have been implicated in degenerative and aging related conditions, such as sarcopenia and neuro-degeneration. While the precise molecular mechanism of deletion formation in mtDNA is still not completely understood, genome motifs such as direct repeat (DR) and stem-loop (SL) have been observed in the neighborhood of deletion breakpoints and thus have been postulated to take part in mutagenesis. In this study, we have analyzed the mitochondrial genomes from four different mammals: human, rhesus monkey, mouse and rat ... Our analysis revealed that in the four species, DR and SL structures are abundant and that their distributions in mtDNA are not statistically different from randomized sequences. However, the average distance between the reported age associated mtDNA breakpoints and their respective nearest DR motifs is significantly shorter than what is expected of random chance in human and rhesus monkey, but not in mouse and rat, indicating the existence of species specific difference in the relationship between DR motifs and deletion breakpoints. In addition, the frequencies of large DRs tend to decrease with increasing lifespan among the four mammals studied here, further suggesting an evolutionary selection against stable mtDNA misalignments associated with long DRs in long-living animals."

FURTHER WORK ON EPIGENETIC CHANGES THAT OCCUR WITH AGING
Thursday, April 26, 2012
http://www.fightaging.org/archives/2012/04/further-work-on-epigenetic-changes-that-occur-with-aging.php
Via ScienceDaily: researchers "have identified a group of 'aging' genes that are switched on and off by natural mechanisms called epigenetic factors, influencing the rate of healthy aging and potential longevity. The study also suggests these epigenetic processes - that can be caused by external factors such as diet, lifestyle and environment - are likely to be initiated from an early age and continue through a person's life. The researchers say that the epigenetic changes they have identified could be used as potential 'markers' of biological aging and in the future could be possible targets for anti-aging therapies. ... the study looked at 172 twins aged 32 to 80 from the TwinsUK cohort. The researchers looked for epigenetic changes in the twins' DNA, and performed epigenome-wide association scans to analyze these changes in relation to chronological age. They identified 490 age related epigenetic changes. They also analysed DNA modifications in age related traits and found that epigenetic changes in four genes relate to cholesterol, lung function and maternal longevity. To try to identify when these epigenetic changes may be triggered, the researchers replicated the study in 44 younger twins, aged 22 to 61, and found that many of the 490 age related epigenetic changes were also present in this younger group. The researchers say these results suggest that while many age related epigenetic changes happen naturally with age throughout a person's life, a proportion of these changes may be initiated early in life."

INSIGHTS INTO AGING FROM THE STUDY OF FLIES
Thursday, April 26, 2012
http://www.fightaging.org/archives/2012/04/insights-into-aging-from-the-study-of-flies.php
An open access review paper looks at how the study of fly aging has informed the life sciences: "it is likely that not all senescent physiological changes revealed in flies can be simply translated to humans. However, flies and humans often show very similar age-related physiological phenotypes suggesting that at least some of the basic biological properties and mechanisms that regulate longevity are conserved amongst species. ... It is well-known that advances in medicine and health care have significantly contributed to increased longevity in humans over the last 100 years. There is also a clear trend toward increased life expectancy including an increase in the numbers of people living to an advanced age and the number of people with chronic age-related diseases. These trends emphasize the need to understand the genetic and physiological factors underlying biological aging and particularly, those that promote healthy aging. ... there are three ways to extend lifespan: increasing early survival rate, increasing late survival rate, or delaying senescence. Remarkably, the first two do not affect basic aging processes. For example, the first one leads to a significant increase in mean but not maximum lifespan, while the second one leads to change in a maximum but not mean lifespan. Delayed senescence, in turn, leads to a significant increase in both the mean and maximum lifespan. ... This raises the question as to whether healthspan and delayed senescence are inter related. As stated above, while many genes have been shown to extend lifespan, these may have little or no ability to delay physiological senescence. In other words, the period of functional disability before death may increase despite the fact that the total duration of life is increased. Thus, the search for appropriate biomarkers applicable to monitor functional senescence is highly important with regards to healthy aging and age-related diseases." These cautions are very much focused on the mainstream research goals of slowing the rate of aging through genetic and metabolic alterations; they have little relevance to efforts aimed at producing continuous repair of aging.

RAPAMYCIN AND OXIDATIVE STRESS IN ADULT STEM CELLS
Wednesday, April 25, 2012
http://www.fightaging.org/archives/2012/04/rapamycin-and-oxidative-stress-in-adult-stem-cells.php
Following on from research into the mechanisms of rapamycin released earlier this month, here is more on the way it might generate its benefits to longevity in laboratory mammals: "Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescence in vitro and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age. To test our hypothesis, we exposed mice to rapamycin and then examined the transcriptome of their spermatogonial stem cells (SSCs). Gene expression microarray analysis revealed that numerous oxidative stress response genes were upregulated upon rapamycin treatment ... When we examined the expression of these genes in 55-week-old wild type SSCs, their levels were significantly reduced compared to 3-week-old SSCs, suggesting that their downregulation is coincident with the aging process in adult stem cells. We conclude that rapamycin-induced stimulation of oxidative stress response genes may promote cellular longevity in SSCs, while a decline in gene expression in aged stem cells could reflect the SSCs' diminished potential to alleviate oxidative stress, a hallmark of aging."

LESS HAND OSTEOARTHRITIS IN LONGER-LIVED POPULATIONS
Wednesday, April 25, 2012
http://www.fightaging.org/archives/2012/04/less-hand-osteoarthritis-in-longer-lived-populations.php
Age-related diseases are among the more visible signs of accumulated biological damage that occurs over time - aging is damage. So we should expect to see less of all such conditions in longer lived populations, and here researchers demonstrate that point for osteoarthritis: "Previous studies have reported that centenarians escape the major age-related diseases. No studies on prevalence and severity of osteoarthritis (OA) in longevity population have previously been reported. Because OA is associated with morbidity and mortality, we hypothesized that radiographic hand OA would generally be less prevalent and would develop at a later age in longevity populations vs non-longevity populations. ... Longevity index was calculated as a ratio of the number of individuals aged [greater than] 90 years vs the number of people aged [greater than] 60, expressed per mil. A population with longevity index [greater than] 40 was considered as a longevity population. ... A significant difference in age standardized prevalence of hand OA was found between each pair of studied samples ... We observed that the pattern of radiographic hand OA in longevity populations differs from the pattern in non-longevity populations. On average, first joints with OA appear at an older age, and progression of hand OA [is] slower."

AN UPDATE ON CYTOGRAFT'S ENGINEERED BLOOD VESSELS
Tuesday, April 24, 2012
http://www.fightaging.org/archives/2012/04/an-update-on-cytografts-engineered-blood-vessels.php
Cytograft is one of many regenerative science ventures established in the past fifteen years, and a competitor in the space of growing blood vessels: "A lot of people were skeptical when two young California-based researchers set out more than a decade ago to create a completely human-derived alternative to the synthetic blood vessels commonly used in dialysis patients. Since then, they've done that and more. ... First the team created blood vessels from patients' own skin cells. Then, in June, the company announced that three dialysis patients had received the world's first lab-grown blood vessels made from skin cells from donors, which eliminates the long lead time needed for making vessels from a patient's own cells. And now Cytograft has developed a new technique for making human textiles that promises to reduce the production cost of these vessels by half. ... Cytograft's new approach builds on what already has been proved successful. In 2005, the team began extracting fibroblasts from patients' own skin, cultured those cells into thin sheets, rolled up those sheets, cultured them some more so that they would fuse together, and implanted the lab-grown cylindrical vessels. The vessel-growing process was lengthy, at about seven months, but, because the vessels were derived from the patients' own cells, the implants were easily accepted by the patients' bodies, and they held up to the rigors of dialysis, which requires repeated punctures with large-gauge needles. Then the researchers created allogeneic vessels - ones grown from donor cells - with the hope that they were laying the foundation for an off-the-shelf stockpile of 100 percent human replacement parts. ... By combining these two methods we could make something that is allogeneic, cheaper to produce, and that you could store forever, meaning that the clinician can pull it off the shelves whenever they want. If it is frozen and allogeneic, that is kind of the homerun."

STRUCTURES TO GUIDE NERVE REGROWTH
Tuesday, April 24, 2012
http://www.fightaging.org/archives/2012/04/structures-to-guide-nerve-regrowth.php
Via ScienceDaily: researchers "have developed a method of assisting nerves damaged by traumatic accidents to repair naturally, which could improve the chances of restoring sensation and movement in injured limbs. ... the team describes a new method for making medical devices called nerve guidance conduits or NGCs. The method is based on laser direct writing, which enables the fabrication of complex structures from computer files via the use of CAD/CAM (computer aided design/manufacturing), and has allowed the research team to manufacture NGCs with designs that are far more advanced than previously possible. Currently patients with severe traumatic nerve damage suffer a devastating loss of sensation and/or movement in the affected limb. The traditional course of action, where possible, is to surgically suture or graft the nerve endings together. However, reconstructive surgery often does not result in complete recovery. ... When nerves in the arms or legs are injured they have the ability to re-grow, unlike in the spinal cord; however, they need assistance to do this. We are designing scaffold implants that can bridge an injury site and provide a range of physical and chemical cues for stimulating this regrowth. ... Nerves aren't just like one long cable, they're made up of lots of small cables, similar to how an electrical wire is constructed. Using our new technique we can make a conduit with individual strands so the nerve fibres can form a similar structure to an undamaged nerve. ... Once the nerve is fully regrown, the conduit biodegrades naturally. The team hopes that this approach will significantly increase recovery for a wide range of peripheral nerve injuries."

AUBREY DE GREY TO DEBATE PROFESSOR COLIN BLAKEMORE
Monday, April 23, 2012
http://www.fightaging.org/archives/2012/04/aubrey-de-grey-to-debate-professor-colin-blakemore.php
Oxford University in the UK has a long tradition of formal public debating, and this week the Oxford University Scientific Society will be hosting a debate on longevity science between Aubrey de Grey of the SENS Foundation and Colin Blakemore former head of the Medical Research Council. This will be the first time that a fellow of the British biomedical establishment has risen to the challenge of describing publicly, in a forum where he can be challenged, why intervention against aging is not in fact medicine's most pressing priority - an area of debate in which the UK lags behind the US: "Oxford University Scientific Society is hosting a debate on Wednesday, 25th April, 2012. The debate will begin at 7pm local time (11am Pacific, 2pm Eastern) in the University of Oxford's Sheldonian Theatre; doors open 45 minutes earlier. Dr. Aubrey de Grey will propose the motion 'This house wants to defeat ageing entirely' and Professor Colin Blakemore will be opposing. The debate will be chaired and moderated by Professor Sir Richard Peto. This debate will address whether it is feasible and appropriate to consider ageing as a target of decisive medical intervention, raising the possibility of substantial extension of human lifespan. Aubrey de Grey is currently Chief Science Officer of SENS Foundation, a biomedical research charity that aims to develop, promote, and ensure widespread access to rejuvenation biotechnologies that address the diseases and disabilities of ageing. SENS Foundation aims to bring ageing under comprehensive medical control. Its research agenda consists of the application of regenerative medicine to ageing - not merely slowing the ageing clock, but resetting it to early adulthood. Colin Blakemore is Professor of Neuroscience at the University of Oxford Nuffield Department of Clinical Neurosciences. He is an expert in vision, development of the brain and neurodegenerative disease. He is active in communication of science and is president and adviser to several charities concerned with brain disorders. Prof. Blakemore was formerly Chief Executive of the Medical Research Council, the UK's largest public funder of biomedical research."

COMMENTARY ON THE NAYSAYERS
Monday, April 23, 2012
http://www.fightaging.org/archives/2012/04/commentary-on-the-naysayers.php
From the Daily Mail: "The Elixir of Youth has a terribly bad press. As soon as any scientist mentions that they have discovered a way of making fruit flies or worms or even mice live a bit longer and furthermore states that this might, just might, work in humans (after lots of tests, refinements, clinical trials and so on and anyway it is decades away at best, the caveats will be longer than the original research paper), you can bet a small vat of snake oil that the naysayers will soon weigh in. 'Who wants to live forever? Not me!' one curmudgeonly columnist will opine. 'What would a world be like with all those ancient people walking around, ugh!' will say another writer who, like the first, will have been commissioned mainly on the basis of their own rather advanced years. Because although the bizarre prejudice against anti-ageing research runs deep and wide, it doesn't quite run deep and wide enough for it to be all right for someone the right side of forty, say, to opine that the old really should shuffle off and leave the field clear. Up to now this has been pretty academic as anti-ageing potions have been little more than science fiction but, as an interesting feature in Nature magazine points out, it is beginning to look like a perfect storm of recent serendipitous discoveries and hard-won genetic advanced might - just might - put the holy grail of increasing human lifespan (as opposed to life expectancy, a very different thing) within reach."

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