Fight Aging! Newsletter, January 28th 2013

January 28th 2013

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!



- Natural Death: We Should Be Worried About It
- A Blithe Acceptance of Death and Centralized Control
- On Strengthening the Longevity Research Community
- Discussion
- Latest Headlines from Fight Aging!
- But What About Pushkin?
- Considering Cybernetic Immortality
- On Long-Lived Cancer-Resistant Rodents
- Longer Telomeres, Less Cancer in Calorie Restricted Mice
- More on Central Control and the Acceptance of Death
- Confirming the Importance of Autophagy in Calorie Restriction
- SENS Research Foundation: Reimagine Aging
- Hearing Loss Correlates With Cognitive Decline
- So How Do You Measure Life Span in Fly Studies?
- Using Epigenetics to Search for the Mechanisms of Rheumatoid Arthritis


Here is an extract from one of the better responses to the Edge yearly question for 2013, "what should we be worried about?" - with the implication that there are many things we are not worrying enough about. In this case, aging to death:

Even if the probability of quickly finding a technological method to delay or reverse senescence is low, we have been devoting far too little effort to it. After all, no matter what else we might achieve with our work in life, we soon won't be around to enjoy it. There are other problems on the planet to worry about, but none more personally important. And yet, despite this motivation, there is very little money being spent on longevity research. Because there is no history of success, and because of widely held religious beliefs, government won't fund it. And because achieving success will be difficult, and the marketplace is flooded with false claims, industry has little interest in solving the problem. Although the profit could be astronomical, there is no easy path to attain it, unlike for cosmetic improvements. Over a hundred times more money is spent on R&D for curing baldness than for curing aging. We may someday find ourselves with extended lifespans as an unintended side effect of taking a pill that gives us fuller hair.

This absurd situation is typical for high-risk, high-reward research in an area without an established record of success. Even with strong motivation, financial support is nearly nonexistent. Scientists working on life extension often lack for equipment or a livable salary, and risk their careers by conducting oddball research that repeatedly fails. The problems are hard. But even with limited resources, a handful of scientists are devoting their lives to the pursuit, because of what's at stake. Success will require research on a similar scale as the Manhattan Project, but government and industry won't be supporting it. The greatest hope is that private individuals will step forward and fund the research directly, or through organizations established for that purpose. Maybe an eccentric, farsighted billionaire will want a chance at not dying. Or maybe many people will contribute small amounts to make it happen. This is being done, to some extent, and it gives me hope.

Personally, I know I am not so different than other people. I also have a very difficult time accepting mortality. When I think about all who have and will be lost, and my own impending nonexistence, it makes me ill. It's entirely possible that the hope I have for a technological solution to aging and death is biased by my own aversion to the abyss. Being realistic, given our current rate of technological advance, although I'm hopeful that radical life extension will happen before I die, I think it's more likely that I'll just miss it. Either way, whether aging is cured within my lifetime or afterwards, it won't happen soon enough. Good people are suffering and dying, and that needs to change in a way that's never been done before.


We live in an age in which the majority of people blithely accept the suffering and death of aging as a given, an axiom, something of no great consequence to the arrangement of everyday life, and do much the same for the centralized control over lives and activities undertaken by a small, empowered elite. The latter is not a novel situation - see ancient Sparta, for example - but the sheer, pervasive breadth and depth in which it is presently practiced is an invention of the past few hundred years, made possible through great increases in wealth and technology. The Panopticon state is a modern creation, Sparta only its tiniest seed. Aging is aging, of course, and has been with us since the beginning. But both of these things are far from inconsequential, and indeed they shape our lives to a very great degree.

It is an important point that most people consider it unremarkable and entirely ethical to talk of regimenting society, placing widespread strictures on everyday activities and choices. Part of the struggle faced by researchers and advocates focused on lengthening human life stems from the fact that a large portion of the population sees nothing inherently wrong in forcing other people to act or not act as they see fit - or worse in forcing them to suffer and die to a timetable. It's somewhat irrelevant that the reasons for such would-be tyranny are flimsy and illogical. The real horror is that this is considered normal and reasonable.

Prompting this line of thought, earlier today I stumbled over an unusual argument against working to reverse degenerative aging and extend healthy life. At root it appears to suggest that a higher throughput of human lives is better (for nebulous reasons relating to variety of life and culture at any given moment), and since population will tend to fall off with increasing wealth and longevity we should thus refrain from trying to prevent the tremendous suffering and death caused by aging. As I was thinking what to make of this particular example, it occurred to me that in order to put forward this sort of argument, you really have to be very accepting of the present cost of aging: the pain, the death, the loss. It has to be a trivial axiom, something that isn't all that important, if you can focus instead on incrementally steering the variety of culture present in the world. Further, you would also have to be pretty comfortable with the sort of tyranny needed to force the world to relinquish biotechnology and die to a particular arbitrary schedule.

It is an ongoing failure on our part that people can idly - or not so idly as has been the case in past years - make arguments of this nature without being noted as unethical, evil, and morally bankrupt. You can advocate enforcing the deaths of as many people as you like, and for whatever thin reasons, so long as they are old, or so it seems. Few people will think you any less of an upstanding fellow for doing so.


Building scientific communities with strong ties to the broader public runs in just the same way as building any community in this day and age - which means very differently to the way things used to be. The internet, open data, and cheap global communication allow a whole new layer of activism and effort by small groups of researchers to stand beside the traditional conferences, funding sources, and institutional relationships. The successful research community of today will be a lot more in touch with the public who stand to benefit from its work, and with the advocates and activists who support progress in the field. You might look at calorie restriction research as an example of strong ties between researchers and advocates, leading to a greater number of human research programs and a greater visibility for calorie restriction as a lifestyle choice. Similarly for aging research: efforts like the Methuselah Foundation and SENS Research Foundation have emerged as much from visionaries and support outside the research community as from the work of those within.

It may be easier to build communities these days, but that doesn't mean it's easy. Effort is definitely involved, along with some measure of fortuitous happenstance, the upkeep of watering holes and initiatives, a need for strong personalities to make and maintain diverse connections, the creation of collaboration tools and outreach programs. The list goes on.

Some of the folk at the International Longevity Alliance are enthused by the idea of building more and better threads to link and strengthen the longevity science community. From their point of view there is much yet to be done in terms of opening up collaboration between research groups and between researchers and interested members of the public. For the moment their efforts center around the Denigma resource database. There is a fair amount of this sort of sentiment in the broader research community these days: towards open publishing, greater transparency, relationships established with philanthropists and supporters in the public. It is the mood of the times, enabled by the falling cost of communication and the increasing capacity of the internet. But mood of the times or not, it still takes people to do the work, bang the drum, build the tools.


The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!



Friday, January 25, 2013
From the Russian end of the longevity advocacy community: "A man strives for justice, but the most unjust thing in life is the inevitability of death. Here's a small child, then an adult, he learns, grows up, falls in love, gets married - divorce, have children, he is happy and suffering, dreaming and disappointed, laughing and crying, running, resting, but for all that the fate is death, imminent death due to aging. Monstrous injustice! A man with his life does not deserve death. People put up with this situation, they talk about natural dying, saying that a person must make room. These excuses have the sound of death due to frustration, due to a lack of knowledge about the theoretical possibilities of science, not a desire to act rationally. A person finds it easier to accept death and aging than to begin to act. So the struggle with death and aging: a complex internal decision, the decision to confront the established foundations, the victory of reason over faith and the desire for psychological comfort, the victory over short-term interest. In 20 years it will not matter exactly what you ate today, what color your wallpaper, and where you go to relax - only one thing will be important, how you confronted death in our day. And in a hundred years, nothing that you are or do now will be important if aging is not defeated. "But what about Pushkin? Everyone remembers him!" - Pushkin would love to change places with you, as he is dead while you are alive and can act. The memory of a man is not the man himself. The good works of Pushkin do not help him in any way nor are a compensation for his dying. Conversely, a victory over aging grants a continuation and the opportunity to do many things. Transhumanism is the desire for freedom. Freedom is possibility. Pain, suffering and aging limit our possibilities. Death reduces them to zero. Improving people via the new nano-, bio-, info-technology of the 21st century offers opportunities only dreamed of by philosophers of the past. It is important to take action."

Friday, January 25, 2013
If the 2045 initiative continues onwards as the founder intends, we're all going to be hearing more about what here is called "cybernetic immortality" - copying the data of the mind to run in machinery that is much more robust and longer-lasting than its biological equivalent. I consider the popularity of this goal (as put forward by Ray Kurzweil, for example) something of an existential threat, insofar as it may drain enthusiasm and allies from work on rejuvenation biotechnology now, and in future decades it may become cheaper to build mind-copies than to finalize the means to reverse and prevent aging in our biological bodies. You don't need to fully understand the brain to copy it given powerful enough computers and scanning tools, and you don't need to understand aging much better than we do today to create rejuvenation biotechnology. There are more than enough people in the world who consider a copy of themselves a suitable continuation to support this sort of technology in preference over medicine for rejuvenation. Today a person can choose to support programs like SENS research on the rejuvenation side or the 2045 group on the mind copying side - it's not just talk, it's a rather important choice between aiming for continued survival of the self or aiming for death while a copy of you survives. "Cybernetic immortality - fantasy or scientific problem? I can answer that right away. It is a scientific problem - of approximately the same type as the problem of people going into outer space, which was proposed by Tsiolkovsky at the turn of the 20th century. Why, despite the support of important scientists (such as V. Turchin, C. Joslyn, R. Kurzweil, A. Bolonkin, B. Bainbridge and others), is this idea rejected by many, or at best treated with skepticism? There are many reasons for this. Firstly: the scale of this super-project, which really does verge on fantasy, is too "overwhelming", for the "average" scientific mindset, which is mundane and cautious, and too dependent on the opinion of the scientific management. Anything is proposed nowadays if financing can be secured for it. I'm not even talking about the colossal growth of false science - charlatans, mages, "miracle-workers". All of this throws a shadow on the idea of cybernetic immortality. Furthermore, we are now only at the approach stage of a solution to this problem, specific steps for its development are in many ways only at discussion level, and creative solutions are required. The eternal idea of immortality has been expressed in myths, legends and religious beliefs. Hence the prejudice that it is not compatible with science. What is the basis for the conviction that the problem of cybernetic immortality is a real scientific problem? It does not contradict the principles of science. In fact, it finds a theoretical basis in them - above all, in the fundamental principle of the iso-functionalism of systems, which essentially heralded the beginning of the computer era. The idea of this principle is that the same complex of functions may be reproduced on substrates with different physical properties. Hence the fundamental possibility to reproduce the functions of a living system and the brain on non-biological substrates, which also fully applies to mental functions."

Thursday, January 24, 2013
An open access review paper looks at the rise of mole-rats in cancer and aging research: "Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body-mass. Most notable are the two subterranean species naked mole rat (NMR) and blind mole rat (BMR) which have maximum lifespans of 32 and 21 years, respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils, and hamsters) tumors are a major source of late-life mortality. Here, we review the recent literature on anti-cancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon, and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53) the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells."

Thursday, January 24, 2013
Here's one of the hundreds of examples to show that the practice of calorie restriction improves near all measures of health and slows near all measures of aging: "To carry out the study, researchers used young mice - just three months old - and reduced their caloric intake by 40% before observing them until the end of their life cycle. "We see that mice that undergo caloric restriction show a lower telomere shortening rate than those fed with a normal diet. These mice therefore have longer telomeres as adults, as well as lower rates of chromosome anomalies." To study the effects of this phenomenon on the health of the mammals, researchers observed the incidence of age-related illnesses like cancer. The mice that had been fed a lower calorie intake showed a reduction in the incidence of cancer. Furthermore, these mice also showed a lower incidence of other age-related illnesses such as osteoporosis, greater glucose uptake or improvements in motor coordination. When the researchers carried out these same experiments with a variety of mice that produce more telomerase - a protein that lengthens telomeres and protects chromosomes - they observed that these mice not only enjoyed better health but also lived up to 20% longer. "We believe that such a significant increase in longevity is due to the protective effect against cancer produced by caloric restriction - incidences fall by 40% if we compare them with the mice that produce more telomerase and have a normal diet - and, added to the presence of longer telomeres, this makes the mice live longer and better." It is calculated that there are currently more than 10,000 people in the world on some form of controlled caloric restriction, so the observation of these individuals will be decisive in discovering the effects of this type of diet on humans."

Wednesday, January 23, 2013
Following on from yesterday's post on the pervasive acceptance of both aging to death and centralized control over society, here is another item that illustrates how state control of medical services and their funding via taxation distorts ethics in the matter of life and death. It quickly becomes acceptable to talk about structuring countless deaths to reduce costs - the power of perverse incentives at work. In industries not so dominated by the state, growth in customer needs and outlays is a boon, an opportunity for growth to meet the challenge, but where the state runs things it inevitably means rationing: the incentives operate to make us all worse off. We become inured to this, disturbingly. So you won't find much outrage in response to this sort of thing, and especially not the relevant sort of outrage - that this is what centralized control over medicine and health brings us to, a complete reversal of the eagerness to serve and develop new products that is the characteristic of a free market. "Past successes in reducing smoking have paid off in slower spending growth on associated medical conditions. Has smoking reduction has also slowed the rate of growth in total health care spending? Maybe, but maybe not. [One] component of outlays declines over time due to a healthier population with lower per capita health care costs. However, another component labeled "Effects of greater longevity on outlays" increases over time as smoking-related deaths are averted and more individuals are alive to collect Social Security and consume federally funded health care. After about twelve years, the longevity effect begins to outweigh the per capita spending effect, and federal outlays are actually increased by the reduced prevalence of smoking brought about by the excise tax! Too bad that not smoking couldn't just keep us healthier without prolonging life! Without this dreaded longevity effect, we could unambiguously claim to be saving money in addition to producing greater health. Seriously though, the narrow question of whether reduced prevalence of smoking saves federal dollars hinges on the number of extended life years. Because some policy-makers will evaluate tobacco control programs on whether they save federal dollars, the delayed-mortality effect of reduced smoking is a negative from this perspective. This perverse result is no knock on the CBO study; it simply answers the question asked and is careful to note that "consequences for the federal budget are only one factor that lawmakers may consider when developing policies to promote health.""

Wednesday, January 23, 2013
Autophagy is the collection of processes used by cells to remove and recycle damaged components and unwanted macromolecules. More housekeeping is a better thing, and increased autophagy is linked to many of the genetic and metabolic alterations shown to extend life in laboratory animals. Here researchers confirm once more the importance of autophagy to the health and longevity benefits induced by calorie restriction: "We have previously shown that autophagy is required for chronological longevity in the budding yeast Saccharomyces cerevisiae. Here we examine the requirements for autophagy during extension of chronological life span (CLS) by calorie restriction (CR). We find that autophagy is upregulated by two CR interventions that extend CLS: water wash CR and low glucose CR. Autophagy is required for full extension of CLS during water wash CR under all growth conditions tested. In contrast, autophagy was not uniformly required for full extension of CLS during low glucose CR, depending on the atg allele and strain genetic background. Leucine status influenced CLS during CR. Eliminating the leucine requirement in yeast strains or adding supplemental leucine to growth media extended CLS during CR. In addition, we observed that both water wash and low glucose CR promote mitochondrial respiration proficiency during aging of autophagy-deficient yeast. In general, the extension of CLS by water wash or low glucose CR was inversely related to respiration deficiency in autophagy-deficient cells. Also, autophagy is required for full extension of CLS under non-CR conditions in buffered media, suggesting that extension of CLS during CR is not solely due to reduced medium acidity. Thus, our findings show that autophagy is: (1) induced by CR, (2) required for full extension of CLS by CR in most cases (depending on atg allele, strain, and leucine availability) and, (3) promotes mitochondrial respiration proficiency during aging under CR conditions."

Tuesday, January 22, 2013
The SENS Research Foundation staff have launched their newly updated website: "If this is your first time visiting our site, welcome. If you've been here before, you're no doubt noticing plenty that is new: an updated site design, a variety of new content, a new logo, and a new organizational name. It all centers around a new tagline: reimagine aging. For a public charity, a tagline can be an enormously powerful thing. Our vision and mission statements remain the primary guides to our planning, but the tag is everywhere, on every business card and letter and web page. More than any other document or phrase, it naturally becomes the daily reminder of who we are and what we are about. Of course we are still "advancing rejuvenation biotechnologies" just as vigorously as when we carried that tagline over the last couple years. We still aim to introduce a new premise for the pharma and biotech industries. And now, our successes in our research, our collaborations, our conferences, and our educational programs have made us increasingly aware of the need to refocus our messaging to people being exposed to us for the first time. So we've consulted with a number of talented and insightful PR folks, and they all offered the same basic advice: "You do a great job of telling people what you do. Now tell them why they should care." That's really the root of the aforementioned changes: we want to do a better job of communicating that, together, we can change the way we think about how to treat age-related disease. We can change the basic research premises that have so far prevented any age-related disease from being eradicated. We can improve medicine in some of the most critical but neglected areas and increase human healthspan. It's quite a bit of change, but it all starts when enough of us reimagine aging."

Tuesday, January 22, 2013
Aging is a global phenomenon, occurring throughout the body, which is why correlations between the pace of different manifestations of degenerative aging are likely to happen and not necessarily linked by anything other than the fundamental causes of aging: "[Researchers] studied 1,984 older adults (average age about 77 years) enrolled in a prospective observational study that began in 1997-1998. A total of 1,162 individuals with baseline hearing loss had annual rates of decline in test scores that measured global and executive function that were 41 percent and 32 percent greater, respectively, than those among individuals with normal hearing. Compared to those individuals with normal hearing, individuals with hearing loss at baseline had a 24 percent increased risk for incident cognitive impairment, according to the study results. "Our results demonstrate that hearing loss is independently associated with accelerated cognitive decline and incident cognitive impairment in community-dwelling older adults," the authors comment. "The magnitude of these associations is clinically significant, with individuals having hearing loss demonstrating a 30 percent to 40 percent accelerated rate of cognitive decline and a 24 percent increased risk for incident cognitive impairment during a six-year period compared with individuals having normal hearing." The authors suggest that, on average, individuals with hearing loss would require 7.7 years to decline by five points on the 3MS (the Modified Mini-Mental State Examination, a commonly accepted level of change indicative of cognitive impairment) compared with 10.9 years in individuals with normal hearing."

Monday, January 21, 2013
The nuts and bolts of reliably measuring life span in small, numerous laboratory animals like flies and worms are glossed over in most of the materials presented here. It's more complicated and prone to error than anyone would like it to be, and as for all such undertakings a whole field of knowledge and practice has been established over the years. Here's an interesting video presentation from the Journal of Visualized Experiments: "Individual aging is manifest at the population level as an increase in age-dependent mortality, which is often measured in the laboratory by observing lifespan in large cohorts of age-matched individuals. Experiments that seek to quantify the extent to which genetic or environmental manipulations impact lifespan in simple model organisms have been remarkably successful for understanding the aspects of aging that are conserved across taxa and for inspiring new strategies for extending lifespan and preventing age-associated disease in mammals. The vinegar fly, Drosophila melanogaster, is an attractive model organism for studying the mechanisms of aging due to its relatively short lifespan, convenient husbandry, and facile genetics. However, demographic measures of aging, including age-specific survival and mortality, are extraordinarily susceptible to even minor variations in experimental design and environment, and the maintenance of strict laboratory practices for the duration of aging experiments is required. These considerations, together with the need to practice careful control of genetic background, are essential for generating robust measurements. Indeed, there are many notable controversies surrounding inference from longevity experiments in yeast, worms, flies and mice that have been traced to environmental or genetic artifacts. In this protocol, we describe a set of procedures that have been optimized over many years of measuring longevity in Drosophila using laboratory vials."

Monday, January 21, 2013
Rheumatoid arthritis is a malfunction of the immune system, but like many autoimmune diseases, comparatively little progress has been made towards understanding its causes. Here researchers are using epigenetic surveys to attempt to find genes of interest: " One probable factor involves chemical "tags" that attach to DNA sequences, part of a so-called epigenetic system that helps regulate when and how DNA sequences are "read," how they're used to create proteins and how they affect the onset or progress of disease. To complicate matters, [the] attachment of the tags to particular DNA sequences can itself be regulated by genes. "The details of what causes a particular sequence to be tagged are unclear, but it seems that some tagging events depend on certain DNA sequences. In other words, those tagging events are under genetic control." Other tagging events, however, seem to depend on cellular processes and environmental changes, some of which could be the result, rather than the cause, of disease. To tease apart these two types of tagging events, the researchers catalogued DNA sequences and their tagging patterns in the white blood cells of more than 300 people with and without one form of RA. The team then began filtering out the tags that did not appear to affect RA risk. For example, if tags were seen on the same DNA sequence in those with and without RA, it was assumed that the tags at those sites were irrelevant to the cause or development of the disease. Ultimately, the team identified 10 DNA sites that were tagged differently in RA patients and whose tagging seemed to affect risk for RA. Nine of the 10 sites were within a region of the genome known to play an important role in autoimmune diseases, while the 10th was on a gene that had never before been associated with the disease. "Since RA is a disease in which the body's immune system turns on itself, current treatments often involve suppressing the entire immune system, which can have serious side effects. The results of this study may allow clinicians to instead directly target the culpable genes and/or their tags.""



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