FIGHT AGING! NEWSLETTER
March 28th 2011
The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!
- The Vegas Group: an Approach to Getting Started
- SENS5 Conference and SENS Foundation 2010 Research Report
- We Age Because the World Changes
- Towards Validation of the Role of Nuclear DNA Damage in Aging
- Latest Headlines from Fight Aging!
THE VEGAS GROUP: AN APPROACH TO GETTING STARTED
As I mentioned in last week's newsletter, the Vegas Group is a so far fictional initiative to unite the open biotechnology and longevity science communities. The Vegas Group goal is to pick up development of promising biotechnology for human use at the point at which the formal research community stops, blocked by regulation. One necessary component of the Vegas Group is an open codex of biotechnology methods, tutorials, and best efforts at reverse engineering that, taken as a whole, is appropriate to an amateur and semi-professional community of biotech developers. The following Fight Aging! post considers how to go about making that happen:
"I can envisage a guiding council of advisors putting together a plan for the hierarchy of topics they would like to see in the Vegas Group codex, from basic methods in biotechnology through to best attempt reverse engineering of things we know to be possible and that have been published: such as Cuervo's work on restoring youthful levels of autophagy, or protofection to replace mitochondrial DNA. The end result of that process might look something like a distillation of Fight Aging! mixed with the very elegant materials produced by the Science for Life Extension Foundation.
"Codex project volunteers would then run an ongoing process of hiring post-graduates and interested researchers to write, and passing the results to starving authors who improve the output to a quality suitable for the open biotechnology community. There would of course be some back and forth between the post-graduates and the starving authors in order to reduce the inevitable translation errors, but I see this as a viable way to produce a body of knowledge that is sufficiently good to begin with - not perfect, not even necessarily very good, but sufficient.
"Since only a comparatively limited reach of biotechnology is under consideration, the cost of bootstrapping such a project might be less than a few hundred thousand dollars. The things I would need to understand before getting seriously underway on a Vegas Group codex are largely related to validating that price tag. A few hundred thousand dollars would mean that it is worth starting with ten thousand dollars, some volunteers, spare time, and raising funds as we go based on the quality of work exhibited."
If you find this interesting, let me know. Enough interested voices would merit starting a mailing list for discussions on how best to make this - and the broader Vegas Group concept - a reality.
SENS5 CONFERENCE AND SENS FOUNDATION 2010 RESEARCH REPORT
The SENS Foundation will be hosting the SENS5 conference on longevity science later this year: the program is already filled out with presentations by leading life science researchers, registration is open, and the early registration rate still applies. While you are over at the SENS Foundation website to take a look, note that the Foundation volunteers recently released a research report for most of 2010. If you'd like a better grasp on where donated funds are going, and the status of ongoing research, I recommend you read it:
"I'm delighted to be able to share with you our research report, prepared for the first 10 months of 2010, by Tanya Jones (our Director of Research Operations), working with our researchers and my CSO Team. I thought it would be of interest to our supporters, and serve as a precursor to our 2010 Year End Report, which is currently under production as part of our finalizing our 2010 accounts.
"SENS Foundation conducts intramural research in its Research Center in Mountain View, California. The primary focus of our intramural work is LysoSENS - investigating novel lysosomal hydrolases against intracellular aggregates that impair cell function - and we recently produced a detailed and comprehensive LysoSENS planning document in collaboration with our extramural project at Rice University.
"We have also arranged for research in the MitoSENS strand - obviating mitochondrial DNA deletions - to be conducted at the Research Center, following the negotiation of a transfer agreement with Dr Corral-Debrinski covering materials produced, and used in, previous successful work by her group. Dr Matthew 'Oki' O'Connor joined us in September to initiate this project."
WE AGE BECAUSE THE WORLD CHANGES
I thought I would direct your attention to a very readable open access paper that presents one of the competing viewpoints on the origins of aging:
"Aging is an inevitability, or so we have to assume: the processes of evolution blindly but efficiently explore the space of possible living creatures, and have been doing so for a very, very long time. Surely a very long-lived or ageless species would have a great advantage in evolutionary competition, its individual members able to produce descendants for far longer than their competitors in a short-lived species that ages. Yet virtually all species - with only a very few exceptions - age in easily measured ways. The species that age are also the species that have won in evolutionary terms, and therefore prospered and spread. Why is this?"
TOWARDS VALIDATION OF THE ROLE OF NUCLEAR DNA DAMAGE IN AGING
There is some debate over whether nuclear DNA damage, which accumulates with age, is a significant cause of aging. This debate exists due to the lack of a good experiment to show that reducing nuclear DNA damage - and only nuclear DNA damage - extends life in laboratory animals. While calorie restriction, for example, does reduce the rate at which nuclear DNA damage accumulates, it also changes nearly everything else in the operation of metabolism. The following Fight Aging! post looks at a discovery that may let researchers produce a firm answer on nuclear DNA damage and aging:
"A process called acetylation regulates the maintenance of our DNA [and] determines the degree of fidelity of both DNA replication and repair. The finding builds on past research, which established that as humans evolved, we created two routes for DNA replication and repair - a standard route that eliminates some damage and a moderate amount of errors, and an elite route that eliminates the large majority of damage and errors from our DNA. Only the small portion of our DNA that directs the creation of all the proteins we are made of - proteins in blood cells, heart cells, liver cells and so on - takes the elite route, which uses much more energy and so 'costs' the body more. The remaining majority of our DNA, which is not responsible for creating proteins, takes the standard route, which requires fewer resources. ... acetylation directs which proteins take which route, favoring the protection of DNA that creates proteins by shuttling them down the elite, more accurate course. ... If we found a way to improve the protection of DNA that guides protein production, basically boosting what our body already does to eliminate errors, it could help us live longer. A medication that would cause a small alteration in this acetylation-based regulatory mechanism might change the average onset of cancers or neurological diseases to well beyond the current human lifespan."
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!
AN UPDATE ON GERM CELLS AND LONGEVITY
Friday, March 25, 2011
Researchers continue to investigate the link between germ cells and longevity in lower animals. In this open access paper, changes to fat metabolism are implicated as an important mechanism: "Removing the germ line of Caenorhabditis elegans extends its lifespan by approximately 60%. Eliminating germ cells also increases the lifespan of Drosophila, suggesting that a conserved mechanism links the germ line to longevity ... Reproduction and aging are two processes that seem to be closely intertwined. Experiments in Caenorhabditis elegans and Drosophila have shown that depletion of the germ line increases lifespan and that this process depends on insulin and lipophilic-hormone signaling. Recently, it was demonstrated that when germline stem cells (GSCs) cease to proliferate, fat metabolism is altered and this affects longevity. In this study, we have identified a nuclear hormone receptor, NHR-80, that mediates longevity through depletion of the germ line by promoting fatty acid desaturation. ... Our results reinforce the notion that fat metabolism is profoundly altered in response to GSC proliferation, and the data contribute to a better understanding of the molecular relationship between reproduction, fat metabolism, and aging."
IMMUNE THERAPY VERSUS PANCREATIC CANCER
Friday, March 25, 2011
An example of the sort of immune system engineering that is presently taking place in the laboratory: "Until this research, we thought the immune system needed to attack the cancer directly in order to be effective. Now we know that isn't necessarily so. Attacking the dense tissues surrounding the cancer is another approach, similar to attacking a brick wall by dissolving the mortar in the wall. Ultimately, the immune system was able to eat away at this tissue surrounding the cancer, and the tumors fell apart as a result of that assault. These results provide fresh insight to build new immune therapies for cancer. ... pancreatic cancer patients received standard gemcitabine chemotherapy with an experimental antibody [that] binds and stimulates a cell surface receptor called CD40, which is a key regulator of T-cell activation. The team initially hypothesized that the CD40 antibodies would turn on the T cells and allow them to attack the tumor. The treatment appeared to work, with some patients' tumors shrinking substantially and the vast majority of tumors losing metabolic activity after therapy, although all of the responding patients eventually relapsed. When the researchers looked at post-treatment tumor samples, obtained via biopsy or surgical removal, there were no T cells to be seen. Instead, they saw an abundance of another white blood cell known as macrophages. ... When the investigators treated mice that developed pancreatic cancer with gemcitabine in combination with CD40 antibodies, the results looked like those of the human trial. Some mouse tumors shrank and were found to be loaded with macrophages but contained few or no T cells. Closer inspection showed that the macrophages were attacking what is known as the tumor stroma, the supporting tissue around the tumor. Pancreatic tumors secrete chemical signals that draw macrophages to the tumor site, but if left to their own devices, these macrophages would protect the tumor. However, treating the mice (or patients) with CD40 antibodies seemed to flip that system on its head. ... It is something of a Trojan horse approach. The tumor is still calling in macrophages, but now we've used the CD40 receptor to re-educate those macrophages to attack - not promote - the tumor."
NUCLEAR DNA DAMAGE, AGING, AND STEM CELLS
Thursday, March 24, 2011
Nuclear DNA damage accumulates with age, but is it a cause of aging? This open access paper illustrates why there is a question - as for many studies, the results do not point unambiguously in one direction or another. "Accumulation of DNA damage leading to adult stem cell exhaustion has been proposed to be a principal mechanism of aging. Here we tested this hypothesis in healthy individuals of different ages by examining unrepaired DNA double-strand breaks (DSBs) in hematopoietic stem/progenitor cells matured in their physiological microenvironment. ... The highest inter-individual variations for non-telomeric DNA damage were observed in middle-aged donors, [where] the individual DSB repair capacity appears to determine the extent of DNA damage accrual. However, analyzing different stem/progenitor subpopulations obtained from healthy elderly (>70 years), we observed an only modest increase in DNA damage accrual, [but] sustained DNA repair efficiencies, suggesting that healthy lifestyle may slow down the natural aging process. ... Based on these findings we conclude that age-related non-telomeric DNA damage accrual accompanies physiological stem cell aging in humans. Moreover, aging may alter the functional capacity of human stem cells to repair DSBs, thereby deteriorating an important genome protection mechanism leading to exceeding DNA damage accumulation. However, the great inter-individual variations in middle-aged individuals suggest that additional cell-intrinsic mechanisms and/or extrinsic factors contribute to the age-associated DNA damage accumulation." Meaning that nuclear DNA damage may or may not be a primary cause of aging, and may or may not be important in comparison to other factors.
TOWARDS STEM CELL THERAPY FOR MACULAR DEGENERATION
Thursday, March 24, 2011
Small steps: "The notion of transplanting adult stem cells to treat or even cure age-related macular degeneration has taken a significant step toward becoming a reality. ... researchers have demonstrated, for the first time, the ability to create retinal cells derived from human-induced pluripotent stem cells that mimic the eye cells that die and cause loss of sight. Age-related macular degeneration (AMD) [gradually] destroys sharp, central vision needed for seeing objects clearly and for common daily tasks such as reading and driving. AMD progresses with death of retinal pigment epithelium (RPE), a dark color layer of cells which nourishes the visual cells in the retina. While some treatments can help slow its progression, there is no cure. The discovery of human induced pluripotent stem (hiPS) cells has opened a new avenue for the treatment of degenerative diseases, like AMD, by using a patient's own stem cells to generate tissues and cells for transplantation. For transplantation to be viable in age-related macular degeneration, researchers have to first figure out how to program the naive hiPS cells to function and possess the characteristics of the native retinal pigment epithelium, RPE, the cells that die off and lead to AMD. ... This is the first time that hiPS-RPE cells have been produced with the characteristics and functioning of the RPE cells in the eye. That makes these cells promising candidates for retinal regeneration therapies in age-related macular degeneration."
THE UNRELIABILITY OF MANY STUDIES OF RODENT LONGEVITY
Wednesday, March 23, 2011
As noted in this paper, many researchers still fail to control for calorie intake in their studies - and thus their experimental results are largely worthless, given the impact of even mild calorie restriction on the life spans of laboratory animals: "Much of the literature describing the search for agents that increase the life span of rodents was found to suffer from confounds. One-hundred-six studies, absent 20 contradictory melatonin studies, of compounds or combinations of compounds were reviewed. Only six studies reported both life span extension and food consumption data, thereby excluding the potential effects of caloric restriction. Six other studies reported life span extension without a change in body weight. However, weight can be an unreliable surrogate measure of caloric consumption. Twenty studies reported that food consumption or weight was unchanged, but it was unclear whether these data were anecdotal or systematic. Twenty-nine reported extended life span likely due to induced caloric restriction. Thirty-six studies reported no effect on life span, and three a decrease. The remaining studies suffer from more serious confounds. Though still widely cited, studies showing life span extension using short-lived or 'enfeebled' rodents have not been shown to predict longevity effects in long-lived animals. We suggest improvements in experimental design that will enhance the reliability of the rodent life span literature. First, animals should receive measured quantities of food and its consumption monitored, preferably daily, and reported. Weights should be measured regularly and reported. Second, a genetically heterogeneous, long-lived rodent should be utilized. Third, chemically defined diets should be used. Fourth, a positive control (e.g., a calorically restricted group) is highly desirable. ... These procedures should improve the reliability of the scientific literature and accelerate the identification of longevity and health span-enhancing agents."
A POPULAR SCIENCE ARTICLE ON AUTOPHAGY AND LONGEVITY
Wednesday, March 23, 2011
From Science News: "the cells of organisms from yeast to humans regularly engage in self-cannibalism. Cells chew on bits of their cytoplasm - the jellylike substance that fills their bellies - and dine on their own internal organs ... It may sound macabre, but gorging on one's own innards, a process called autophagy, is a means of self-preservation, cleansing and stress management. ... A munch here gets rid of garbage that might otherwise clog the system. A nibble there rids cells of malfunctioning parts. One chomp disposes of invading microbes. In lean times, all that stands between a cell and starvation may be the ability to bite off and recycle bits of itself. And in the last decade or so it has become clear that self-eating can also make the difference between health and disease. ... Starvation inhibits an important biological signaling system, known as the mTOR pathway - named for a key protein involved in regulating cell growth and survival, cell movement and protein production. The inhibition of mTOR sets off a cascade of reactions inside the cell that end in autophagy and may be crucial to prolonging cell life and ultimately fending off cancer. A drug that inhibits mTOR, called rapamycin, has been shown to extend life span in mice. It and calorie restriction are [amongst a handful of] methods proven to prolong longevity, suggesting both may work through autophagy to make cells live longer."
A NECESSARY LEVEL OF SKEPTICISM
Tuesday, March 22, 2011
Much as we'd like it to be otherwise, humans don't live as long as many people like to claim that they do. The tendency to make and believe outlandish claims of human longevity is examined in this open access paper: "People have long been fascinated with claims to extreme longevity. Ancient Roman historians attempted to tally reports of extreme age in local villages. Medieval European alchemists kept tabs on reports of centenarians, possibly to find a 'cure' for old age (the Fountain of Youth). Inexplicably, various historians and even 'scientists' such as Roger Bacon accepted outlandish and wild reports of extreme age prima facie, without a critical examination or inquiry into whether the ages reported were true. It was not until the 18th century, with the advent of demographers such as Georges Buffon (1707-1788) that a limit to the human life span was proposed, with Buffon stating that 'the man who does not die of incidental diseases reaches everywhere the age of ninety or one hundred years' .. [Even today] political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. ... Understanding various causes of false extreme age claims is important for placing current, past, and future extreme longevity claims in context and for providing a necessary level of skepticism. ... To provide a current context to unsubstantiated age claims, we provide here some statistics concerning supercentenarian (a person age 110 years or older) prevalence. Kestenbaum and Ferguson at the U.S. Social Security Administration reported Medicare data indicating that, in 2000, there were 32,920 centenarians and out of these, 105 or 0.3% were 110 years old and older. Of 2,700 people who reportedly reached the age of 110+ years between 1980 and 1999, according to the SSA, only 355 (13%) could be confirmed."
DON'T GET FAT, AND DON'T STAY FAT
Tuesday, March 22, 2011
More data to quantify just how bad excess body fat is for you: "researchers have found the number of years individuals live with obesity is directly associated with the risk of mortality. The research shows that the duration of obesity is a strong predictor of mortality, independent of the actual level of Body Mass Index (BMI). As the onset of obesity occurs earlier and the number of years lived with obesity increases, the risk of mortality associated with adult obesity in contemporary populations is expected to increase compared with previous decades. Using data from the Framingham Heart Study, 5209 participants were followed up for 48 years from 1948. The current study however only included participants who were free from pre-existing diseases of diabetes, cardiovascular diseases and cancer. The research showed that for those who had a medium number of years lived with obesity (between five years and 14.9 years), the risk of mortality more than doubled than for those who had never been obese. The risk of mortality almost tripled for those with the longest duration of obesity (more than 15 years). Furthermore, the research showed for every additional two years lived with obesity, the risk of mortality increased by between six and seven per cent. ... Before now, we did not know whether being obese for longer was any worse for you health than simply being obese. However, this research shows for the first time that being obese for longer increases your risk of mortality, no matter how heavy you actually are."
THE STATE OF RESEARCH INTO HUMAN LONGEVITY IS PRESENTLY FAR FROM IDEAL
Monday, March 21, 2011
It is always good to see some of the important ideas making their way out into the world, even in forms that are not ideal. Here, for example, the idea that all is not as it should be in medical and aging research, and that far more could be done to tackle aging: "Scientists who study the biology of aging - the basic mechanisms of how our cells and tissues change with age - believe the aging process is modifiable. ... Even better, scores of peer-reviewed studies have proven that decelerating the aging process in lab animals also offers huge health benefits, dramatically delaying and lowering their incidence of chronic disease. ... If we could achieve the same exciting results in humans, we could transform the lives of older people and achieve what aging researchers call a longer healthspan. ... So what's stopping us? ... Putting a man on the moon was a defining national goal in the 20th century; in the 21st century, it should be decoding the biology of aging to find the fountain of health. ... Unfortunately, this potentially transformative work is a poor stepchild in the biomedical research enterprise. Older Americans tend to develop multiple chronic diseases [but] most research funding gets siloed into grants that study individual diseases, produce therapies that treat only one aspect of a patient's complex condition, and may add few, if any, very expensive months to life. Aging research has far greater potential to repay the public's investment than disease-centric research, because the best defense is a good offense. Getting at the root cause of a range of diseases can ultimately help us keep millions of people from developing those conditions in the first place. Although the National Institutes of Health budget exceeds $31 billion annually, the vast majority of those funds are allocated to research on specific diseases rather than the basic biology of aging, despite its potential to provide many preventive and curative strategies."
AN OPTIMISTIC RESPONSE TO DATA ON HUMAN LONGEVITY
Monday, March 21, 2011
Singularity Hub has an optimistic response to recent announced updates to life expectancy data: "A new record high in US life expectancy begs the question, what will your children do with 0.2 more years of living? Well, that's not exactly how life expectancy works, but it's still a time to celebrate! ... While these statistics tell us that a child born in 2009 has a good chance of living into their seventies, here at the Hub we think the real expectancy should be a hundred years more than that as upcoming technologies will continue to boost lifespans, as we fight illness, poverty, and hunger. For now, the National Vital Statistics System report shows us what progress we've already made. 10 of the 15 top causes of death are dropping, infant mortality is falling, and most age groups are doing better as well. Statistically speaking, it's a great time to be alive. And it's only going to get better. ... While the causes of death are many, and the factors behind its variation complex, it is reassuring to see that there are many emergent technologies that may help us not only live longer, but healthier as well. We're getting closer to being able to grow new organs to replace faulty ones, whether their damage comes from genetics or our own malfeasance. Or perhaps we'll augment our organs with machines, letting cybernetics extend our lives and expand our capabilities. ... There are institutions dedicated to taking all these emerging forms of technology and using them to help the billions in the developing world. Other groups are struggling to find the root causes of aging, and extend not just life expectancy, but our maximum lifespan as well."