Longevity Meme Newsletter, January 3rd 2011

January 3rd 2011

The Longevity Meme 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 the Longevity Meme.

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- Wealth Does Not Grant Vision
- A Little Nihilism for a Cold Monday
- The Methuselah Foundation Needs a Technical Volunteer
- Fundraising for Microglia Transplant Research
- Latest Headlines from Fight Aging!


All that wealth gives you is a lever - it provides neither the will, foresight, or knowledge needed to use that lever in a way that will benefit all of humanity:


"I think there's a certain tendency to believe that wealthy people have attributes and talents that in fact they don't possess: they have a great deal of one important thing, so therefore they must have more of all the others, right? But across a broad spectrum of the wealthy, you are probably not going to see greater intelligence, drive, wit ... or vision. Wealth doesn't grant you any of these things if you didn't have them beforehand, and a few decades of being alive and socially active should teach you that none are a necessary prerequisite for becoming wealthy. I'm not even all that certain that they help.

"If you think over your experiences in talking about longevity science with people, you're probably in just the same boat as me: most of the folk you'll meet don't believe that near-term progress is possible, don't like to think about aging and death anyway, and are locked into a view of their own lives that has them progressing and ending just like those of their grandparents. There is no vision, they learned the shape of the box they will live in while they were young and in school, and have little interest in change. In this, your friends and acquaintances are not at all different from any given selection of high net worth individuals. ... So why be disappointed that those high net worth individuals are just as unlikely to help of their own accord, or understand the possible future of rejuvenation biotechnology? Wealth is not magic gold and blessings from the fae; these people grew up in the same society as the rest of us, and thus are on average just as blinkered - in need of education and persuasion - when it comes to aging and longevity science."


Nihilism, yes, but also interesting reading material:


"It is fairly easy to slide from the question 'why live longer?' to the question 'why live?' If you're not so sold on being alive at the present time, it may follow that you're also not so much in favor of being alive for longer in the future. Sadly, many people are on the fence when it comes to their continued existence as thinking, conscious entities: ambivalent until threatened with impending death, at which point deep-seated survival instincts take over, but ultimately vaguely looking forward to their end. Others call into question the morality of creating new people when they are doomed to inevitable suffering and death, and this cheerful topic leads us to a brace of posts at Depressed Metabolism."

You should take a look.


Are you smart, reliable, and skilled with LAMP (Linux, Apache, MySQL, and PHP) coding and development? If so, the Methuselah Foundation has need of you:


"The Methuselah Foundation, founded back in 2003, aims to promote and support scientific progress towards defeating age-related disease, repairing the damage of aging, and greatly extending the healthy human life span. To that end the Foundation has raised more than $10 million in funding pledges, and their initiatives include the Mprize for longevity science, the recently launched NewOrgan Prize, investment in tissue engineering startups such as Organovo, and - prior to the establishment of the SENS Foundation as a separate entity - the funding of Aubrey de Grey's research program for rejuvenation biotechnology.

"These activities, and the networking to support them behind the scenes, have had a great impact upon the state of the aging research community, media treatment of longevity science, and public perception of the plausibility of medical research aimed at reversing aging. Thanks to the efforts of the Foundation volunteers and thousands of supporters, the environment for longevity science today is far improved over that of ten years ago. That in turn means that our chances of seeing working rejuvenation medicine within our lifetimes are also improved.

"A brief inspection of the website will tell you that the Foundation runs on a LAMP stack - Linux, Apache, MySQL, and PHP. What you won't see is the largely invisible bulk of packaged code, integrations, mail, archives, and other systems required to run a distributed volunteer non-profit organization. Add that to the newer online projects in the works or on the drawing board, and keeping things running as well as moving forward begins to require a considerable amount of time from people who know how to code or maintain a server. ... From a practical standpoint, this means is that the Foundation needs a reliable, smart volunteer programmer: someone who is comfortable building their own websites from scratch, working independently as a part of a geographically distributed team, can contribute to the process of developing plans and designs, and confidently touch every part of the LAMP stack in the doing of it."


The Immortality Institute's latest fundraising project aims to raise $8,000, which will be matched by another $8,000 from the Institute coffers. This money will fund a research project to evaluate transplant of microglia as a way to attack some of the damage that builds up in an aging brain:


"Cognitive functions of the brain decline with age. One of the protective cell types in the brain are called microglia cells. However, these microglia cells also loose function with age. Our aim is to replace non-functional microglia with new and young microglia cells derived from adult stem cells. We will inject these young microglia cells into 'Alzheimer mice' - a model for Alzheimers disease. After giving the cells some time to work, we will sacrifice the mice and measure microglia activity, neurogenesis, proliferation of neuroprogenitors and plaque density in the brain. A reduction in plaque density of Alzheimer mice would be a first proof that the transplanted microglia are performing their expected function.

"The full PDF format research proposal is available: the work will be carried out by a graduate research assistant and will cost $16,000. This is the essence of our present era of biotechnology: a task that would have occupied a whole laboratory and its equipment in the 1980s, and cost a great deal of money if it was even possible at all, is now something that a skilled graduate-level life scientist can organize and run himself within an established lab. The times are changing - and this plummeting cost of research will only continue."

If you think this is beneficial, then donate! Modest donations from dozens of people have raised a quarter of the needed total already, so jump in and help out.


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, December 31, 2010
A response to recent arguments on the biological basis for women's longevity advantage: "The most influential line of reasoning in gerontology is known as Disposable Soma Theory (DST). In brief, the theory states that aging is caused by accumulation of random damage, which is counteracted by repair. Repair is costly and the organism allocates exactly the needed amount of energetic resources. Recently, DST was applied to explain why women live longer than men. Women are less disposable than men, so they need a better repair and thus live longer. It might seem slightly repetitive that women live longer because they are less disposable because females need better health for reproduction. I will discuss that this explanation is also erroneous. But to start with, the name of the theory (disposable soma) is ambiguous because soma is disposable by definition: soma versus germ line. All theories of aging are more or less disposable soma theories. ... The question is why is soma disposable and what makes it disposable. According to DST, it is allocation of resources from repair to other needs. Here we will discuss drastically different cause. ... So why do women live longer? ... In brief, high accidental death rate is associated with faster aging in different species, from worms to mammals. The same is applicable to longevity of males versus females. The accidental death rate, from accidents, violence, combat, is higher in young men than in women. Historically, it was much higher. Higher accidental death rate in young men may have led them to be larger and stronger than women. ... mTOR drives cellular size growth and muscle hypertrophy, including testosterone-induced hypertrophy ... I suggest that hyper-active mTOR contributes to physical robustness of young males, allowing them to fight and compete. But hyper-active mTOR is beneficial earlier in life at the cost of accelerated aging. ... In other words, accelerated aging in males relative to females could be a byproduct of physical robustness to prevent death from extrinsic causes." As you can see there is still plenty of room for debate in even apparently simple, straightforward questions in aging science.

Friday, December 31, 2010
A recent review: "It has been almost two decades since dietary restriction was first shown to increase Drosophila lifespan. Since then, understanding this phenomenon advanced as groups worked to identify what quality of restricted diet matters: calories or a specific nutrient. The problem is complex because is it difficult to measure what a fly actually consumes. A powerful solution uses the geometric framework of nutrition where diets in many combinations can be tested for their effects on lifespan and reproduction while measuring intake. Applied to Drosophila, it is now clear that specific nutrients, not calories, mediate longevity. The geometric framework also reveals a nutritional basis for the trade-off between reproduction and lifespan. This complements a stable isotope analysis that tracked the allocation of nitrogen, carbon and essential amino acids into eggs versus reproduction. Together these studies show this is not possible to explain how DR extends lifespan through a mechanism were resources are simply reallocated to somatic maintenance away from reproduction. Although promising in principle, genetic analysis of DR mechanisms has had limited success. To be productive studies must include enough diets at appropriate concentrations. In reviewing the best data, there is little evidence to date for any gene to be required for DR to increase Drosophila lifespan [as opposed to the situation in nematode worms], including insulin signaling or 4eBP. Strong analyses of genes required for DR should be a priority in future research with Drosophila and this may be made most robust by considering the effect of mutants in the context of the geometric framework."

Thursday, December 30, 2010
Long term projections of life span continue to trend upward as the actuaries revise their opinions on biotechnology - but I believe they still fail to account for potential revolutionary advances in medicine that lie ahead. The level of uncertainty at least is fairly well grasped now within the actuarial industry, but for various political reasons it is only slowly seeping into official projections: "In the first official projection of its kind, the Department for Work and Pensions today forecasts that almost a fifth of Britons will celebrate their 100th birthday. Of the 17 per cent of the population who will become centenarians, about three million are under the age of 16, and 5.5 million are aged between 16 and 50. In total, about half a million people a year will be celebrating their 100th birthday by 2066, compared with about 10,000 now. Nearly 8,000 of them will reach their 110th birthday. ... Predicting the rate of increase of life expectancy used to be much easier because the rate of increase did not vary much. But some areas of biotechnology are increasingly driven by the same kinds of advances that make computer power increase so rapidly. ... It is difficult to look down the road 20 years and guess every way that biological manipulations will speed up by orders of magnitude or which treatments will become very easy as a consequence. But it seems reasonable to expect that in the 21st century we will experience a revolution in biotechnology in par with the revolution in computer technology that began in the middle of the 20th century and continues to this day." Retirement as an institution will radically change, and those countries that practice the iniquity of forcing people out of work at a certain age will also have to change.

Thursday, December 30, 2010
This study looks for measures that might reflect rates at which new medical technology makes its way into the marketplace, and checks for correlation with rising life expectancy. The result is what you might expect - that more rapid adoption of new technology means longer lives: "The rate of increase of longevity has varied considerably across U.S. states since 1991. This paper examines the effect of the quality of medical care, behavioral risk factors (obesity, smoking, and AIDS incidence), and other variables (education, income, and health insurance coverage) on life expectancy and medical expenditure using longitudinal state-level data. We examine the effects of three different measures of the quality of medical care. The first is the average quality of diagnostic imaging procedures, defined as the fraction of procedures that are advanced procedures. The second is the average quality of practicing physicians, defined as the fraction of physicians that were trained at top-ranked medical schools. The third is the mean vintage (FDA approval year) of outpatient and inpatient prescription drugs. Life expectancy increased more rapidly in states where (1) the fraction of Medicare diagnostic imaging procedures that were advanced procedures increased more rapidly; (2) the vintage of self- and provider-administered drugs increased more rapidly; and (3) the quality of medical schools previously attended by physicians increased more rapidly. States with larger increases in the quality of diagnostic procedures, drugs, and physicians did not have larger increases in per capita medical expenditure. We perform several tests of the robustness of the life expectancy model. Controlling for per capita health expenditure (the 'quantity' of healthcare), and eliminating the influence of infant mortality, has virtually no effect on the healthcare quality coefficients. Controlling for the adoption of an important nonmedical innovation also has little influence on the estimated effects of medical innovation adoption on life expectancy."

Wednesday, December 29, 2010
Failing grip strength in older people is a good biomarker for frailty in all bodily systems and consequently higher mortality levels. Separately, advanced glycation end-products (AGEs) accumulate in the body's tissues with age, and impact a number of important biological processes - so we'd expect to see correlation between rising AGE levels and failing grip strength even if they have no direct link and are completely distinct aspects of age-related degeneration. Here, researchers show that this correlation stretches back into earlier adult life: "Aging is associated with decreased skeletal muscle function. Increased levels of advanced glycation end products (AGEs) in skeletal muscle tissue are observed with advancing age and in diabetes. Although serum AGE level is negatively associated with grip strength in elderly people, it is unknown whether this association is present in adult males. To determine the relationship between AGE accumulation in tissue and muscle strength and power among Japanese adult men. Skin autofluorescence (AF) (a noninvasive method for measuring tissue AGEs), grip strength, and leg extension power were measured in Japanese adult men ... Among Japanese adult men, participants with higher skin AF had lower muscle strength and power, indicating a relationship between AGE accumulation and muscle strength and power. A long-term prospective study is required to clarify the causality." If forced to guess, I'd suggest that the other biochemical and cellular causes of aging have a greater impact than AGEs on muscle strength - but that remains to be established, and we should still be trying to fix everything regardless of the outcome of that investigation.

Wednesday, December 29, 2010
The cellular recycling process of autophagy appears to be important in many of the known methods of slowing aging through manipulation of metabolism. AMPK is a protein involved in the control of metabolism that is important and of interest in aging research, and this may be because of its influence over autophagy: researchers "have discovered how AMPK, a metabolic master switch that springs into gear when cells run low on energy, revs up a cellular recycling program to free up essential molecular building blocks in times of need. ... AMPK activates a cellular recycling process known as autophagy by activating an enzyme known as ATG1, that jumpstarts the process. The newly uncovered direct molecular connection between AMPK and ATG1 is significant because dysfunctions in both AMPK signaling and autophagy are implicated in a plethora of aging-related diseases, including type II diabetes, cancer, and neurodegenerative diseases such Parkinson's and Alzheimers. ... the group focused on large intracellular structures called mitochondria, whose role is to generate energy. ... Mitochondria are easily damaged in detoxifying tissues like liver. A critical way that defective mitochondria are turned over is through a special form of autophagy called mitophagy. ... In that case, cells would envelope their unhealthy mitochondria in a membrane, dump them in a cellular acid pit, and recycle the remains. If AMPK initiated the process, cells genetically engineered to lack AMPK might show altered mitochondrial turnover compared to normal cells. And that is precisely what the researchers saw: liver cells in which AMPK had been eliminated contained too many mitochondria, many of which looked spindly, indicating they were moribund, and confirming that AMPK was directing autophagic waste disposal."

Tuesday, December 28, 2010
A range of biological differences have been noted that distinguish exceptionally long-lived families from the rest of us poor mortals. Here is another: "The development of medical interventions for the preservation of disease-free longevity would be facilitated by markers that predict healthy aging. Altered protein N-glycosylation patterns have been found with increasing age and several disease states. Here we investigate whether glycans derived from the total glycoprotein pool in plasma mark familial longevity and distinguish healthy from unhealthy aging. Total plasma N-glycan profiles of 2396 middle aged participants in the Leiden Longevity Study (LLS) were obtained... After normalization and batch correction, several regression strategies were applied to evaluate associations between glycan patterns, familial longevity and healthy aging. Two N-glycan features (LC-7 and LC-8) were identified to be more abundant in plasma of the offspring of long-lived individuals as compared to controls. ... Furthermore, a decrease in levels of LC-8 was associated with the occurrence of myocardial infarction, indicating that plasma glycosylation patterns do not only mark familial longevity, but may also reflect healthy aging. In conclusion, we describe two glycan features, of which increased levels mark familial longevity while decreased levels of one of these features mark the presence of cardiovascular disease."

Tuesday, December 28, 2010
From Michael Batin, and machine-translated: "For the Foundation Science for Life Extension, the main outcome [for this past year] was the first Russian unique operation on transplantation of the trachea, grown from [the patient's own stem cells]. Operation using the method of Professor Paolo Macchiarini held in December in Research Center of Surgery named after Academician BV Petrovsky, RAMS (Moscow). In order to bring this technique to Russia, the Foundation has worked a half years. We fully fund the project and organize the interaction of all participants - RAMS RNTSH, Clinics Karredzhi University of Florence, pharmaceutical companies, manufacturers of biomaterials. Total project costs amounted to around 250 thousand euros. ... Patient was a 26-year-old girl. In 2006, she was hit by a car, she was very seriously injured, survived clinical death, a few months has been in a coma. Breathe on their own she could not ... Now the patient before discharge - she can speak much better breathing, can walk and perform physical activity. ... This operation - the beginning of the introduction into clinical practice of regenerative medicine technologies, which opens up broad prospects for the treatment of serious illnesses associated with the loss of vital organs and tissues, and allows scientific and clinical institutions of Russia to enter the International Consortium for Regenerative Medicine." The process used here is decellularization, in which a donor trachea is stripped of its cells, leaving only the structure of the extracellular matrix. That is then repopulated with the patient's own cells, which avoids the normal issues of transplant rejection.

Monday, December 27, 2010
Researchers look for root causes of the longevity enhancement produced by eliminating the male contribution to the mouse genome: "A recent study by Kawahara and Kono (2010) reports that mice artificially produced with two sets of female genomes have an increased average lifespan of 28%. Moreover, these animals exhibit a smaller body size, a trait also observed in several other long-lived mouse models. One hypothesis is that alterations in the expression of paternally methylated imprinted genes are responsible for the life-extension of bi-maternal mice. Considering the similarities in postnatal growth retardation between mice with mutations in the Rasgrf1 imprinted gene and bi-maternal mice, Rasgrf1 is the most likely culprit for the low body weight and extended lifespan of bi-maternal mice. Rasgrf1 is a neuronal guanine-nucleotide exchange factor that induces Ras signaling in a calcium-dependent manner and has been implicated in learning and memory. Like other long-lived mouse strains, Rasgrf1 mutants are known to have low growth hormone and IGF-1 levels and the Rasgrf1 yeast homolog CDC25 had been previously associated with lifespan. Therefore, although the evidence is not conclusive, it does point towards the involvement of Rasgrf1 in the regulation of longevity, hypothetically through a mechanism similar to that observed in other long-lived mice of low GH/IGF-1 signaling causing a low body weight and life-extension."

Monday, December 27, 2010
One view of strategy in the development of calorie restriction mimetic treatments: "Calorie restriction (CR) remains the most robust environmental intervention for altering aging processes and increasing healthspan and lifespan. Emerging from progress made in many nonhuman models, current research has expanded to formal, controlled human studies of CR. Since long-term CR requires a major commitment of will power and long-term negative consequences remain to be determined, the concept of a calorie restriction mimetic (CRM) has become a new area of investigation within gerontology. We have proposed that a CRM is a compound that mimics metabolic, hormonal, and physiological effects of CR, activates stress response pathways observed in CR and enhances stress protection, produces CR-like effects on longevity, reduces age-related disease, and maintains more youthful function, all without significantly reducing food intake. Over 12 years ago, we introduced the concept of glycolytic inhibition as a strategy for developing mimetics of CR. We have argued that inhibiting energy utilization as far upstream as possible might offer a broader range of CR-like effects as opposed to targeting a singular molecular target downstream. As the first candidate CRM, 2-deoxyglucose, a known anti-glycolytic, provided a remarkable phenotype of CR, but turned out to produce cardiotoxicity in rats. Since the introduction of 2DG as a candidate CRM, many different targets for development have now been proposed at more downstream sites, including insulin receptor sensitizers, sirtuin activators, and inhibitors of mTOR."



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