FIGHT AGING! NEWSLETTER
June 27th 2011
The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!
- Fundraising Success for Microglia Transplant Study
- DNA Methylation as a Biomarker of Age and Aging
- Calorie Restriction Slows Kidney Decline
- The Forgotten Past, the Nascent Future
- Latest Headlines from Fight Aging!
FUNDRAISING SUCCESS FOR MICROGLIA TRANSPLANT STUDY
I'm pleased to see that the Immortality Institute has succeeded in raising funds for their latest research funding project, a study of the effectiveness of microglia transplants to reverse some of the aspects of degenerative aging in the brains of mice:
"Which is good news all round. I've mentioned this effort in past months, so you can head on back into the archives for more details on the funded research. We live in an age in which a large range of meaningful early-stage work in biotechnology can be performed for comparatively little money - a few tens of thousands of dollars, or less. A single young researcher with lab access can validate theories, determine whether a line of research has promise, or make new connections in a field - and all in a matter of a few months to half a year of work, as one of a number of ongoing projects.
"Most importantly, the new reality of low costs means that people of everyday means can band together in small associations to fund the research that they find important, on a project by project basis. This sort of grassroots, bottom-up organization is greatly aided by the internet, but crowdsourced philanthropy for science in detail is only just in its infancy. Projects like those undertaken by the Immortality Institute volunteers are the first signs of the true future of research funding - a detailed and glorious patchwork in which everyone can pick and choose the exact projects they wish to fund, and in doing so learn more about the science behind the causes they support."
DNA METHYLATION AS A BIOMARKER OF AGE AND AGING
DNA methylation is one of the changes that happens in our biochemistry with aging, probably a sign that the adaptive mechanisms of our cells - and the biological systems that they make up - are trying to copy with increasing levels of damage by altering their programming. This change can be measured, and that is important in aging research:
"You have at least two ages: your chronological age, how long you have lived, and what we might call your biological age - which is a measure of how damaged you are. Aging, meaning the process of physical degeneration, is really just a matter of damage at the level of cells and molecular machinery. The more damage, the greater your biological age. If you are 56, you might have the damage load of the average 50 year old or the average 60 year old. Or worse, or better - and in either case that will reflect in your current health and remaining life span.
"In actual fact, biological age is probably far more complex than this. There is every reason to expect different systems in your body to suffer different rates of damage accumulation. Consider the immune system in AIDS patients for example, which is prematurely aged into exhaustion and frailty. That is an extreme example of differential rates of damage: you would expect to find smaller differences in levels of accumulated damage in the biological components of a healthy person. But the differences are there.
"Recognize that a lot of what I have said above is theory. Anyone who claims to be able to measure your biological age is largely blowing smoke: there's no standard for such a thing, and not much in the way of biomarkers of aging. Biomarkers are measurable aspects of our biology that can be scaled against age or remaining life expectancy - and so might be used to determine a subject's chronological age, or how much longer they might expect to live. The absence of good biomarkers poses a strategic challenge for the ongoing development of longevity science, because in order to efficiently evaluate a potential therapy to slow or reverse aging, researchers need to rapidly understand its actual effects on healthy life span. Sitting around and waiting is the only presently foolproof strategy, and that is one of the reasons that even mouse studies of longevity therapies are very expensive. No-one wants to run an experiment for going on four years if there is a way to call a halt after a few months and some biomarker measurements.
"That difference in experimental run time represents a large sum of money in every sizable study, not to mention the opportunity cost in research that might otherwise move ahead, but must wait for years for results to arrive. Further, when you stop to consider human studies, you'll see that that the present state of affairs rules out a wide range of possible trials - 'wait and see' isn't viable when the time frame is decades. This is why we should all be interested in progress towards the establishment of biomarkers for aging, and today I'll point you to recent work on DNA methylation, undertaken with that aim in mind. You might recall that DNA methylation correlates with age and age-related frailty, and here researchers greatly improve upon the precision of that correlation."
CALORIE RESTRICTION SLOWS KIDNEY DECLINE
It is essentially accurate to say that calorie restriction slows aging. Aging is no more than a progressive accumulation of unrepaired damage, and the practice of calorie restriction reduces the pace at which that damage builds up. This most likely has as much to do with modification of cellular repair and recycling mechanisms as anything else, but what it means is that researchers are finding almost every detailed examination of changes and harm that happens with aging shows it to be slower for the calorie restricted. For example, calorie restriction slows down the accumulation of a very specific marker of damage and decline in the kidney:
"Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been associated with age-related cellular damage and dysfunction with reports of increased levels of apoptosis, necrosis, and inflammation in the aged kidney. Bioactive sphingolipids have been shown to regulate these same cellular processes, and have also been suggested to play a role in aging and cellular senescence. We hypothesized that alterations in kidney sphingolipids play a role in the declining kidney function that occurs during aging. ... Importantly, caloric restriction, previously shown to prevent the declining kidney function seen in aging, inhibits accumulation of [two sphingolipids examined in this study] and prevents the age-associated elevation of enzymes involved in their synthesis."
THE FORGOTTEN PAST, THE NASCENT FUTURE
There is already a younger generation of people interested in scientific methods to extend life that has forgotten the generation that came before - their struggles and their goals:
"Modern advocacy for engineered longevity and methods of preventing permanent death (such as cryonics) began in earnest in the 1970s, give or take, and has thus been around for long enough to establish a distinct and fascinating cultural past that most younger people are unaware of. The last decades of the last century are being buried rapidly indeed. The more thoughtful older folk who lived through that past there are sponsoring a growing range of initiatives to help ensure the continuation and growth of this present community of advocates, supporters, writers, and researchers. It is in everyone's interest for there to be more people working on human life extension, talking about it, and advocating for longer, healthier lives. In this sense, the future is something that is constructed, not something that just unfolds without any effort on anyone's part - and that includes the future of communities. If there is growth it is because people planned carefully and worked hard to create that growth."
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!
REVERSING TYPE 2 DIABETES
Friday, June 24, 2011
Type 2 diabetes is as close to a disease of choice as you're likely to find: provided that you adopt a sensible lifestyle of good diet and exercise then you are never going to suffer the condition, barring extremely bad luck in your genes. Similarly, if you are headed down the path towards diabetes, you can turn back by changing the way you live your life. Here's evidence that the turn can be made quite late if made aggressively enough: "An extreme eight-week diet of 600 calories a day can reverse Type 2 diabetes in people newly diagnosed with the disease .... the low-calorie diet reduced fat levels in the pancreas and liver, which helped insulin production return to normal. Seven out of 11 people studied were free of diabetes three months later. ... More research is needed to see whether the reversal is permanent, say experts. ... The 11 participants in the study were all diagnosed with Type 2 diabetes within the previous four years. They cut their food intake drastically for two months, eating only liquid diet drinks and non-starchy vegetables. ... After one week of the diet, researchers found that the pre-breakfast blood sugar levels of all participants had returned to normal. MRI scans of their pancreases also revealed that the fat levels in the organ had decreased from around 8% - an elevated level - to a more normal 6%. Three months after the end of the diet, when participants had returned to eating normally and received advice on healthy eating and portion size, most no longer suffered from the condition. ... This diet was only used to test the hypothesis that if people lose substantial weight they will lose their diabetes. Although this study involved people diagnosed with diabetes within the last four years, there is potential for people with longer-standing diabetes to turn things around too."
MEIOSIS AND LONGEVITY IN YEAST
Friday, June 24, 2011
Lower forms of life have stages that don't exist in higher animals - such as meiosis in yeast, or the dauer stage in nematodes. Researchers have found they can manipulate longevity by manipulating the molecular machinery associated with these states, but it's generally felt that this is of lesser relevance to mammals. Here is an example of the type: "Human cells have a finite lifespan: They can only divide a certain number of times before they die. However, that lifespan is reset when reproductive cells are formed, which is why the children of a 20-year-old man have the same life expectancy as those of an 80-year-old man. How that resetting occurs in human cells is not known, but MIT biologists have now found a gene that appears to control this process in yeast. Furthermore, by turning on that gene in aged yeast cells, they were able to double their usual lifespan. ... When yeast cells reproduce, they undergo a special type of cell division called meiosis, which produces spores. The MIT team found that the signs of cellular aging disappear at the very end of meiosis. ... The researchers discovered that a gene called NDT80 is activated at the same time that the rejuvenation occurs. When they turned on this gene in aged cells that were not reproducing, the cells lived twice as long as normal. ... In aged cells with activated NDT80, the nucleolar damage was the only age-related change that disappeared. That suggests that nucleolar changes are the primary force behind the aging process." Which is an interesting conclusion, but given all the other evidence for mechanisms of aging in mammals, I'm not sure it's going to translate well into higher animals.
EAT LESS, LIVE LONGER?
Thursday, June 23, 2011
A cautious popular science article on calorie restriction: "Caloric restriction as a research discipline has actually been around for ages. The first demonstration of extending lifespan and improving health in rats by cutting calories was back in 1934, and since then the finding has been repeated in numerous species up to and including non-human primates. Animals subjected to caloric restriction while maintaining adequate vitamin, mineral, and protein intakes not only live longer, healthier lives, they also maintain vitality to an older age and have fewer visible signs of aging - such as white fur - compared to better-fed siblings. It is worth noting that we are not just talking about shedding a few pounds here. Animal studies show that, almost up to the point of frank starvation, the more calorie restriction the better when it comes to extending lifespan and health. ... Virtually every animal study ever done on caloric restriction has shown benefits for health and longevity, and now we have emerging studies showing that even intermittent caloric restriction may be beneficial, so it would be almost surprising if humans turned out to be the only species to have a negative response. Unlike research animals, however, humans don't live alone in pre-paid houses with the right kind of food carefully provided by scientists, so if caloric restriction is to be a feasible strategy for maintaining health as we age it has to be feasible to implement - in other words, doable and practical in real lives in the real world." People who write about calorie restriction without having made a serious attempt at trying it invariably exaggerate the difficulty. Practicing calorie restriction is both "doable and practical," and requires no more investment of time and willpower than any modestly challenging hobby.
NOTES ON THE 40TH ANNUAL MEETING OF THE AMERICAN AGING ASSOCIATION
Thursday, June 23, 2011
From the IEET: "The focus of the 40th annual meeting of the American Aging Association, held a few weeks ago in North Carolina, was emerging concepts in the mechanisms of aging. Most of the usual topics in aging were covered, such as dietary restriction, inflammation, stress resistance, homeostasis and proteasome activity, sarcopenia, and neural degeneration. Newer methods like microRNAs and genome sequencing were employed to investigate gene expression variance with aging and genetic signatures of longevity. Aging as a field continues to mature including by using a systems approach to tracing conserved pathways across organisms, sharpening definitions of sarcopenia, frailty, and healthspan, and distinguishing interventions by age tier (early-onset versus late-onset). A pre-conference session on late-onset intervention concluded that there are numerous benefits to deriving such interventions."
MORE ON FINANCIAL PLANNING AND CRYONICS
Wednesday, June 22, 2011
It is good to see that cryonics is now sufficiently widely known that business magazines are willing to write articles on the financial engineering and legal explorations associated with establishing a successful cryopreservation: "Financial planning, like most disciplines, generally relies on the assumption that the dead will remain that way. Some people, however, are not as willing to accept this premise. Cryonicists believe science will eventually give us the ability to reanimate the dead. In preparation for this possibility, they elect to have their bodies, or sometimes merely their heads, stored in extreme low temperatures so that, when the time comes, they can be restored to life. Some anticipate a future in which their bodies will be thawed and cured of their ailments, while others see the process as akin to data storage, preserving the organic record of their thoughts and memories until these can be downloaded onto some new medium. ... the legal and financial questions surrounding cryonics require serious believers to make plans in the present, before they start their hiatus. Since cryonics remains well outside the mainstream, most end-of-life matters have yet to be thought through as temporary-suspension-of-life concerns. Ordinarily, at death, social security numbers are cancelled and made public, and citizenship privileges such as voting are revoked (at least in most jurisdictions). What would the temporarily dead need to do to put their legal status on ice along with their bodies?" If you want a serious consideration of the details, you might look at some of Rudi Hoffman's articles on cryonics and financial planning.
A PROFILE OF LAURA DEMING, THIEL FOUNDATION FELLOWSHIP RECIPIENT
Wednesday, June 22, 2011
At Forbes, a profile of one of the Thiel Fellowship recipients who focuses on longevity science: "Deming started working in a research lab when she was 12, enrolled at MIT at age 14 and last month, the now 17 year-old was awarded one of 24 $100,000 Thiel Foundation Fellowships for her work in the realm of anti-aging, specifically efforts to identify the genes that control aging and to use discoveries about age-defying therapies effective in worms to unlock the key to extending the human lifespan ... I had a fantastic childhood. Growing up, I had complete freedom to investigate whatever I was interested in, so I puzzled around with math and science, and got hooked on biology. When I was 12, Cynthia Kenyon, one of the coolest people I know, let me come to her lab. She works with a wonderful little worm called C. elegans, so I got to spend the next few years peering down a microscope at the fascinating critters. Then I went to MIT. I'm leaving as a physics major after a whirlwind couple of years spent exploring the magical properties of the quantum realm. ... 'I'd been mulling over what to do after college. The optimal scenario I came up with was exactly what the 20 Under 20 program offers; an opportunity to spend two years working to extend the human healthspan.' She will take up her award in the fall and will initially focus on identifying promising anti-aging research projects that are close to commercialization."
MORE ON LEUCINE INTAKE AND MUSCLE MASS
Tuesday, June 21, 2011
You might recall that age-related issues with the body's processing of the dietary amino acid leucine were implicated as a possible contributing cause of sarcopenia, the progressive loss of muscle mass with age. More leucine in the diet seemed to be a possible treatment - here that is tried for cancer patients, with a generally positive outcome: "Maintenance of muscle mass is crucial to improving outcome and quality of life in cancer patients. Stimulating muscle protein synthesis is the metabolic basis for maintaining muscle mass, but in cancer patients normal dietary intake has minimal effects on muscle protein synthesis. Adding leucine to high protein supplements stimulates muscle protein synthesis in healthy older subjects. The objective was to determine if a specially formulated medical food, high in leucine and protein, stimulates muscle protein synthesis acutely in individuals with cancer to a greater extent than a conventional medical food. ... . Ingestion of the experimental medical food increased muscle protein [synthesis]. In contrast, ingestion of the control medical food did not ... Conclusions: In cancer patients, conventional nutritional supplementation is ineffective in stimulating muscle protein synthesis. This anabolic resistance can be overcome with a specially formulated nutritional supplement."
SPURRING MUSCLE REGROWTH
Tuesday, June 21, 2011
A possible strategy for regrowing muscle lost to injury: "Cpl. Isaias Hernandez was 19 when he lost 70 percent of the muscles in his right thigh, and doctors initially recommended amputation ... But Hernandez worked with researchers at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, who were able to seed his remaining muscles with a cocktail of proteins and growth factors derived from pig bladders. ... [Researchers are working to] develop an implantable extracellular matrix that can re-grow tissue. The matrix is a biological scaffold, enriched with proteins and growth factors, which recruits stem cells and other cell precursors to the site of the injury. ... The therapy stimulates further tissue regeneration, essentially rebuilding the lost muscle. Skeletal muscle does not normally regenerate after an accident, so the ability to re-grow this tissue, complete with nerve branches and tendons, would be a real breakthrough. ... Before injecting the extracellular matrix, doctors had him perform a rigorous exercise regimen to build up his remaining leg muscle ... Then surgeons made an incision in his thigh and inserted the matrix. After a few weeks, Hernandez's leg began growing 'in bulk and strength.'" This is a similar strategy to that used to regenerate a fingertip some years ago - a result that hasn't been replicated to date. This may renew interest in the work in the broader research community.
WALL STREET JOURNAL ON IMMUNE THERAPIES
Monday, June 20, 2011
A general interest article on immunotherapy from the Wall Street Journal: "Scientists are scrambling to develop medications that fight cancer by spurring the body's immune system, a form of treatment that some cancer specialists believe may hold the key to keeping a patient permanently disease-free. ... immunotherapy drugs are being developed for a number of other cancers, including lung, brain and kidney cancers. Unlike most traditional therapies that attack a cancer directly, immunotherapy uses the body's own internal defenses to ward off the disease, with the ultimate hope of building up a long-term resistance to the cancer. ... The growing interest in immunotherapy comes even as traditional cancer-targeting drugs have become more effective. Still, such drugs often just delay the ultimate recurrence of the disease as tumors develop resistance to the treatment, or some cancer cells survive the therapy and regrow. The hope is that the immune system's long-term activity against the cancer could stop this cycle. ... Immunotherapies can work in several ways. They can help the immune system increase its response so that it fights the cancer better; they can stop cancers from slowing down or halting the immune system's activation; or they can help the immune system find the tumor and kill it. ... The idea of using the immune system first drew significant research attention in the mid- to late-1990s, but multiple failures led to widespread discouragement ... Developments in recent years have produced the momentum that researchers believe will allow it to reach the next level of more powerful treatments and, ultimately, their combination with both traditional drugs and other immunotherapies."
IMMUNOTHERAPY CURES PROSTATE CANCER IN MICE
Monday, June 20, 2011
A good demonstrations of the promise of immune therapies, training the immune system to destroy very specific types of cell: researchers "cured well-established prostate tumors in mice using a human vaccine with no apparent side effects. This novel cancer treatment approach encourages the immune system to rid itself of prostate tumors without assistance from toxic chemotherapies and radiation treatments. Such a treatment model could some day help people to live tumor free with fewer side effects than those experienced from current therapies. ... We are hopeful that this will overcome some of the major hurdles which we have seen with immunotherapy cancer research ... Among the team's findings: no trace of autoimmune diseases in the mice. The murine T-cells attacked only cancerous prostate cells, leaving the healthy tissue unharmed. To develop this new approach, geneticists assembled snippets of genetic code from healthy human prostate tissue into a complementary DNA (cDNA) library. These bits of cDNA were then inserted into a swarm of vesicular stomatitis viruses (VSV), which were cultured and reintroduced into the test mice as a vaccine during a series of intravenous injections. Development of comprehensive cDNA libraries from healthy human prostate tissue represents the key to successful immunotherapy. All infections, allergens and tissues, including tumors, have a unique fingerprint called an antigen - a molecular protein tag that triggers a response from the body's immune system. [Researchers] deployed the human vaccine prostate cancer antigens through the mutated VSV vector to raise a full-on assault from the mice's T-cells. After exposure to the mutated viruses, the animals' immune systems recognized the antigens expressed in the virus and produced a potent immune response to attack the prostate tumors."