FIGHT AGING! NEWSLETTER
April 25th 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!
- A Mailing List for Vegas Group Development
- The Importance of Improvement
- Measuring the Benefits of a Good Lifestyle
- Older Parents, Not So Good
- Latest Headlines from Fight Aging!
A MAILING LIST FOR VEGAS GROUP DEVELOPMENT
The Vegas Group will ultimately be a broad initiative to bring the best longevity-enhancing techniques already demonstrated in the laboratory to the growing open biotechnology movement, with the aim of sufficiently documenting and translating this work to make it available for medical tourism to clinics outside the US. This will be a way to work around the restrictive state of regulation in the US, where aging is not recognized as a disease, treatments will not be approved for use, and promising technologies are therefore not funded.
In these opening, early days, the Vegas Group is focused on documentation: producing how-to materials for the best methodologies in longevity science that will enable the amateur and semi-professional community of biotech enthusiasts to become more involved. The first interested volunteers are presently discussing organization, longevity science, and how best to make the Vegas Group a reality in the Google group mailing list for the project:
We're looking for writers, editors, people with a biotech or life science background, and web developers for a forthcoming website - amongst other skill sets. If you are interested and can help, or even if you would just like to follow along at home, please do join and take a look at the archives to see where the present discussions are headed.
THE IMPORTANCE OF IMPROVEMENT
The debate over human enhancement is important in ongoing efforts to persuade people of the merits of engineered human longevity:
"It is unfortunate and noteworthy that the loudest institutional voices in Western culture seem to have an aversion to human enhancement. It is the ideal of equality run rampant, heading for its inevitable Harrison Bergeron endpoint - equality by leveling down to the lowest and preventing new heights from being achieved. ... This rejection of human enhancement is in essence a rejection of the urge to improvement - and is thus one of a number of important hurdles standing in the way of widespread support for the development of rejuvenation biotechnology. Living longer than your parents did? That's an enhancement, and a great many talking heads would like to see laws written to prevent such technologies from ever seeing the light of day.
"The bureaucrats of the FDA do not recognize aging as a disease, and so will not approve treatments for it. In a culture that is hostile to human enhancement, winning support for the reversal of aging will be that much harder. This is one of many ways in which freedom matters greatly in medical research. Under the systems of regulation in place in the largest markets of the world, researchers and commercial developers are far from free to turn proven science into commercial products, and far from free to convince their fellow countrymen to try something new. We humans are the species that improves ourselves and creates value from our surroundings. That is our defining characteristic - and yet, paradoxically, so much time and effort in this day and age is devoted to sabotaging the engines of progress."
MEASURING THE BENEFITS OF A GOOD LIFESTYLE
The falling cost of data processing and management of information means that researchers can now more accurately quantify the expected benefits of good health practices:
"A study of more than 100,000 men and women over 14 years finds nonsmokers who followed recommendations for cancer prevention had a lower risk of death from cancer, cardiovascular disease, and all-causes. ... The participants were scored on a range from 0 to 8 points to reflect adherence to the American Cancer Society (ACS) cancer prevention guidelines regarding body mass index, physical activity, diet, and alcohol consumption, with 8 points representing adherence to all of the recommendations simultaneously. ... After 14 years, men and women with high compliance scores (7, 8) had a 42% lower risk of death compared to those with low scores (0-2). Risk of cardiovascular disease death were 48% lower among men and 58% lower among women, while the risk of cancer death was 30% lower in men and 24% lower in women."
Turning that around, you can see that the risks to health and future longevity that you adopt by being sedentary, eating too much, and taking on other health risks are fairly sizable. We live in an age on the verge of developing ways to rejuvenate the old - but that won't help you at all if you die before the advent of these technologies. A few years here or there for many of us may mean the difference between centuries of additional health life or missing the boat entirely.
OLDER PARENTS, NOT SO GOOD
Being born to older parents is one of many biological hazards that we cannot do anything about after the fact. Yet.
"One of the predictions of the reliability theory of aging and longevity is that we are all born damaged. ... The models of reliability theory only match up with reality if we assume that life starts with a certain level of preexisting biological damage, and that damage goes some way to determining later health and life expectancy. What happens in early life matters a great deal, it seems. This is why we are interested in such topics as the potential effects of solar radiation on the unborn, and the degree to which historical increases in longevity can be explained by a lower childhood burden of chronic disease. I noticed another interesting data point today in an open access paper: a possible marker for the biological cost of being born to an older mother - something that we know bears an increased risk of health issues.
"Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. ... We found that methylation levels [associated with] 142 genes were significantly correlated with maternal age."
Biotechnology will be a great leveler of opportunity, a grand remover of adversity, offering the chance to repair deleterious consequences of ancestry, birth, and other biological circumstances beyond our control. Systematic alteration of DNA methylation will likely be a commonplace medical technology of the late 2020s, for example. This and many other potentially beneficial manipulations of DNA are almost within reach of the most advanced research groups today - and the biotechnologies of ten or fifteen years from today will far cheaper and more capable than the best machinery now available.
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!
THE CRONA STUDY
Friday, April 22, 2011
A look at current research on the definite health and potential longevity benefits of calorie restriction in humans: "Animals who consume fewer calories live longer and healthier lives. Now, a seminal study at the University of California, San Francisco (UCSF) is testing whether the same is true for extreme dieters. The calorie restriction study centers on two primary questions: What allows people to live in a manner many consider food deprived? And does it slow down aging? Called CRONA (Caloric Restriction with Optimal Nutrition and Aging Study), the investigation is probing the biological processes affected by extremely low caloric intake, including the impact on telomeres - tiny pieces of DNA that protect cell chromosomes. Short telomeres have been linked to a host of health problems including diabetes, heart disease and premature death. The UCSF study is the first to broadly examine the psychological profile of successful extreme dieters, gauging how their cognitive sharpness, impulse control, stress and personality differ from normal eaters and overeaters. ... Testing and data collection will continue through summer. The scientists are still recruiting control subjects who are either obese or 'free eaters' - not restricting food intake but not overweight. Interested parties can email firstname.lastname@example.org. ... We need information about what it takes to change your eating pattern for a long time. There are so many diets out there - people lose weight for six months, then regain it. We need to study what it is about the calorie restrictors that makes them able to do this for years and years." The new information on the biological response to calorie restriction is, I think, much more valuable than yet another study on willpower in humans.
A LOOK AT GARAGE BIOTECHNOLOGY
Friday, April 22, 2011
Small scale efforts by a widespread people outside the academic and industry communities, and open and largely free access to plans and data are the future of biotechnology. It is a data-driven field, and will ultimately look just like the open source software community does today: "Following in the footsteps of revolutionaries like Steve Jobs and Steve Wozniak, who built the first Apple computer in Jobs's garage, and Sergey Brin and Larry Page, who invented Google in a friend's garage, biohackers are attempting bold feats of genetic engineering, drug development, and biotech research in makeshift home laboratories. ... For a few hundred dollars, anyone can send some spit to a sequencing company and receive a complete DNA scan, and then use free software to analyze the results. Custom-made DNA can be mail-ordered off websites, and affordable biotech gear is available on Craigslist and eBay. ... biohackers, like the open-source programmers and software hackers who came before, are united by a profound idealism. They believe in the power of individuals as opposed to corporate interests, in the wisdom of crowds as opposed to the single-mindedness of experts, and in the incentive to do good for the world as opposed to the need to turn a profit. Suspicious of scientific elitism and inspired by the success of open-source computing, the bio DIYers believe that individuals have a fundamental right to biological information, that spreading the tools of biotech to the masses will accelerate the pace of progress, and that the fruits of the biosciences should be delivered into the hands of the people who need them the most."
THE PROMISE OF STEM CELL REJUVENATION
Thursday, April 21, 2011
Stem cell function, necessary to maintain tissue, declines with age. This most likely a part of the evolved balancing act between suppression of cancer and the need to keep tissues repaired and working - as you grow older, forms of molecular damage accumulate, increasing the risk of cancer resulting from the normal operations of cellular proliferation. That balance can already be shifted in mice in very beneficial ways, giving both less cancer and longer lives. While these are the early days yet, in our future lies a fusion of the fields of cancer research and stem cell science that will do the same for humans: "Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell-based therapy of age-related diseases."
TIME WAITS FOR NO ONE
Thursday, April 21, 2011
A reminder: "Biological aging is the greatest health threat to humanity today. It causes more disease and suffering in the world than all infectious diseases (HIV, malaria, etc.) or any other cause (e.g. poverty, war, natural disaster, etc.). The inborn aging process causes cancer, heart disease, stroke, AD, joint pain, vision and hearing impairment, etc. The harms of senescence (even if we exercise and eat a healthy diet) are certain, severe and universal. The diseases of aging afflict both rich and poor, and developed and developing countries. And, unless the biological clocks we have inherited from our Darwinian past are modified, it is highly likely that all future generations of human beings that shall ever live on this planet will suffer one or more of the diseases of aging. In light of the unique health challenges facing the world's aging populations, the most important knowledge humans can acquire today is knowledge about the biology of aging: why do we, as a species, age at the rate we do? why does aging leave our bodies and minds susceptible to disease? And, most importantly, how can we retard or ameliorate the harmful effects of biological aging?"
INVESTIGATING MUSCLE REPAIR AND MAINTENANCE
Wednesday, April 20, 2011
A number of research groups are looking into ways to manipulate muscle regeneration and maintenance, and an advance here could be useful as a therapy to address age-related loss in muscle mass and strength: "Researchers have long questioned why patients with Duchenne muscular dystrophy (DMD) tend to manage well through childhood and adolescence, yet succumb to their disease in early adulthood, or why elderly people who lose muscle strength following bed rest find it difficult or impossible to regain. Now, researchers [are] beginning to find answers in a specialized population of cells called satellite cells. Their findings [suggest] a potential therapeutic target for conditions where muscle deterioration threatens life or quality of life. ... Suspecting a genetic switch that might turn off satellite cell proliferation in these circumstances, the scientists looked to a gene called Ezh2, known to keep the activity of other genes in check. When they genetically inactivated Ezh2 in satellite cells of laboratory mice, the mice failed to repair muscle damage caused by traumatic injury - satellite cells could not proliferate. Ezh2 expression is known to decline during aging, and the new research in mice suggests that therapies to activate Ezh2 and promote satellite cell proliferation might eventually play a role in treating degenerative muscle diseases. ... in the elderly, tweaking the gene in satellite cells would not increase their lifespan, but could increase their quality of life by helping to prevent falls and enabling them to move and walk better and go about their daily activities."
THE WORK OF MICHAEL ROSE
Wednesday, April 20, 2011
A Science 2.0 article looks at the work of researcher Michael Rose over past decades: "Over the years, Rose and his lab have bred fruit flies to live four times the life span of an average fruit fly. Reasoning from those studies, Rose has proposed that, because the life spans of fruit flies have the genetic capability to be extensively prolonged, human life can be manipulated in the same way. ... Wattiaux was a French scientist working at the University of Leuven in Belgium. His study used the same fruit flies that Rose had been working with ... Wattiaux found that when he made each new generation of fruit flies that were the offspring of old parents exclusively, the flies showed an increased life span after each generation. But Wattiaux didn't know why his fruit flies lived longer. He felt that longevity increased because of a nongenetic effect, but he didn't have any direct evidence. Rose did. Wattiaux's results, he saw, showed the importance of the force of natural selection. He believed that, because natural selection stops working at a late age and fails to eliminate genes with detrimental effects, these bad genes would not be removed by natural selection. Instead, they would accumulate. In populations that reproduce early, natural selection declines early. Alternatively, populations that are old when they reproduce will continue to be subject to powerful selection until they begin to reproduce. Thus, by allowing older flies to reproduce over generations, natural selection would continue to choose the flies that are able to breed at a later age - the fittest flies."
INJECTABLE REGENERATIVE FILLER FOR WOUNDS AND DEFECTS IN TISSUE
Tuesday, April 19, 2011
The use of nanoscale scaffolding material mixed with cells - to spur repair of wounds that would otherwise not heal - is becoming more sophisticated: "scientists have made star-shaped, biodegradable Polymer>polymers that can self-assemble into hollow, nanofiber spheres, and when the spheres are injected with cells into wounds, these spheres biodegrade, but the cells live on to form new tissue. ... The procedure gives hope to people with certain types of cartilage injuries for which there aren't good treatments now. ... To repair complex or oddly shaped tissue defects, an injectable cell carrier is desirable to achieve accurate fit and to minimize surgery. [Researchers have been] working on a biomimetic strategy to design a cell matrix - a system that copies biology and supports the cells as they grow and form tissue - using biodegradable nanofibers. ... the nanofibrous hollow microspheres are highly porous, which allows nutrients to enter easily, and they mimic the functions of cellular matrix in the body. Additionally, the nanofibers in these hollow microspheres do not generate much [in the way of] degradation byproducts that could hurt the cells. ... The nanofibrous hollow spheres are combined with cells and then injected into the wound. When the nanofiber spheres, which are slightly bigger than the cells they carry, degrade at the wound site, the cells they are carrying have already gotten a good start growing because the nanofiber spheres provide an environment in which the cells naturally thrive. This approach has been more successful than the traditional cell matrix currently used in tissue growth ... Until now, there has been no way to make such a matrix injectable so it's not been used to deliver cells to complex-shaped wounds."
NF-κB INHIBITION EXTENDS LIFE IN FLIES
Tuesday, April 19, 2011
NF-κB is associated with a range of interesting mechanisms: "Aging is associated with NF-κB-dependent pro-inflammation. Here we demonstrated that inhibition of NF-κB with pyrrolidine dithiocarbamate increases the median lifespan (13-20%) and the age of 90% mortality (11-14%) in Drosophila melanogaster females and males, respectively. ... NF-κB controls the expression of genes involved in innate immunity, inflammation and apoptosis. Such age-dependent pathologies as tissue inflammation and atrophy are caused by over-activation of the NF-κB signaling with age. ... Recent studies suggest that the NF-κB transcription factor controls age-dependent changes in inflammation genes expression. Donato et al showed that an increase of NF-κB dependent genes in human endothelium with age is primarily linked to [decreased] NF-κB inhibition. Age-associated expression of NF-κB-dependent genes cause progression of atherosclerosis in rat. Furthermore, selective inhibition of NF-κB activity in blood vessel endothelial cells prevents atherosclerosis progression. Genetic blockade of NF-κB in the skin of chronologically aged mice reverses the global gene expression program and tissue characteristics to those of young mice ... However, the effect of NF-κB inhibition on the lifespan was not studied before."
AN EXAMPLE OF THE RELEVANCE OF AUTOPHAGY
Monday, April 18, 2011
Time and again, autophagy, the process by which cells recycle their broken machinery, shows up as being important in methods of altering life span in lower animals: "The acetylase inhibitor, spermidine, and the deacetylase activator, resveratrol, both induce autophagy and prolong life span of the model organism Caenorhabditis elegans in an autophagy-dependent fashion. Based on these premises, we investigated the differences and similarities in spermidine and resveratrol-induced autophagy. The deacetylase sirtuin 1 (SIRT1) and its orthologs are required for the autophagy induction by resveratrol but dispensable for autophagy stimulation by spermidine ... SIRT1 is also dispensable for life span extension by spermidine. Mass spectrometry analysis of the human acetylproteome revealed that resveratrol and/or spermidine induce changes in the acetylation of 560 peptides corresponding to 375 different proteins. Among these, 170 proteins are part of the recently elucidated human autophagy protein network. Importantly, spermidine and resveratrol frequently affect the acetylation pattern in a similar fashion. In the cytoplasm, spermidine and resveratrol induce convergent protein de-acetylation more frequently than convergent acetylation, while in the nucleus, acetylation is dominantly triggered by both agents. We surmise that subtle and concerted alterations in the acetylproteome regulate autophagy at multiple levels."
REGENERATING BLOOD VESSELS
Monday, April 18, 2011
Researchers are making progress in understanding the signals needed to spur specific forms of regeneration: they "have discovered a strategy for stimulating the formation of highly functional new blood vessels in tissues that are starved of oxygen. ... a biological factor, called fibroblast growth factor 9 (FGF9), is delivered at the same time that the body is making its own effort at forming new blood vessels in vulnerable or damaged tissue. The result is that an otherwise unsuccessful attempt at regenerating a blood supply becomes a successful one. ... This potential treatment has been termed 'therapeutic angiogenesis'. ... Unfortunately and despite considerable investigation, therapeutic angiogenesis has not as yet been found to be beneficial to patients with coronary artery disease. It appears that new blood vessels that form using approaches to date do not last long, and may not have the ability to control the flow of blood into the areas starved of oxygen. [This latest work] provides a method to overcome these limitations. This strategy is based on paying more attention to the 'supporting' cells of the vessel wall, rather than the endothelial or lining cells of the artery wall. The research team found that by activating the supporting cells, new blood vessel sprouts in adult mice did not shrivel up and disappear but instead lasted for over a year. Furthermore, these regenerating blood vessels were now enveloped by smooth muscle cells that gave them the ability to constrict and relax, a critical process that ensures the right amount of blood and oxygen gets to the tissues. ... FGF9 seemed to 'awaken' the supporting cells and stimulated their wrapping around the otherwise fragile blood vessel wall."