Fight Aging! Newsletter, April 2nd 2012

FIGHT AGING! NEWSLETTER
April 2nd 2012

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!

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CONTENT

- SENS Foundation Annual Report for 2011 Released
- SENS5 Video: AGES and Aging
- More Commentary on Russia 2045
- On Indifference to the Future
- Discussion
- Latest Headlines from Fight Aging!

SENS FOUNDATION ANNUAL REPORT FOR 2011 RELEASED

The SENS Foundation budget is growing, and projects are being initiated in all of the areas of rejuvenation biotechnology described by the Strategies for Engineered Negligible Senescence proposals:

https://www.fightaging.org/archives/2012/03/sens-foundation-annual-report-for-2011-released.php

"You might say that the past three years have been SENS Foundation's 'Mercury project' - our proof-of-concept phase - during which we've worked to establish the feasibility of our line of inquiry through our research, education, and outreach programs. And in this we have been successful. The Thiel Foundation's substantial and continued funding has been met both with broader-based support and more key individual backers. Edward James Olmos has volunteered to lend his voice to our message. Jason Hope's philanthropic gift has launched our glucosepane research program at Cambridge and Yale Universities. We've worked hard to build new collaborations and outreach opportunities, and 2012 will show a significant research project in every major category of damage in the SENS technological proposal.

"What has changed [in the SENS Foundation messaging] is the fact that we now have specific research, details, and ongoing proof-of-concept work to discuss. SENS Foundation has matured as an organization. We have moved well beyond the point of needing to defend the SENS platform as worth testing out in the laboratory; we have won that battle. Instead, we are discussing how SENS Foundation can best go about its work of building an industry and creating a comprehensive, practical suite of rejuvenation biotechnologies. And so, I no longer discuss and emphasize what the future might hold. Rather, I discuss and emphasize what is going on right now at the SENS Foundation Research Center in Mountain View, California, and in Foundation-funded laboratories across the world.

"We are delighted that SENS Foundation was able to make expenditures of $1,518,000 in 2011. This was an increase of over $400,000 from 2010, overwhelmingly in support of direct research and conference projects. ... We greatly appreciate the support of the many individuals who contributed to our mission. We would like to thank Peter Thiel, Jason Hope, the Methuselah Foundation, and all of our contributors and volunteers for their on-going generosity. We expect a significant increase in both revenues and expenses for 2012, as we begin to see distributions from a de Grey family trust, under a grant from SENSF-UK. This support will be in addition to the contributions we receive from other sources."

By way of comparison with the 2010 report showed a $1 million budget or so for that year, about a third of which went to LysoSENS research - working on the foundation of a biomedical remediation strategy that could use bacterial enzymes to safely break down the age-related build up of harmful aggregates in the body. That build up is one of the fundamental causes of aging, but suitable biotechnologies such as biomedical remedication can and should be developed to address it. A successful technology platform for therapies will allow for both extension of healthy life span and restoration of health to those who are already damaged and suffering.

It has to be said, I'm pleased to see work on finding a safe agent to break down glucosepane moving forward. The lack of significant progress anywhere in the world on AGE breakers targeting the most common AGE - glucosepane - over the past decade has been enormously frustrating. It is one of the few areas of SENS in which the traditional and massive drug development industry is perfectly suited to the task. It may as well have had a big red target painted on it given the size of the market for a working drug that actually, legitimately, literally reversed skin aging - amongst other important body parts such as blood vessels - and yet nothing much has happened.

SENS5 VIDEO: AGES AND AGING

Since we are on the topic of AGEs and what to do about them, here is a counterpoint to the usefulness of the existing drug development industry - made by the UK researchers working in collaboration with the SENS Fundation to break down glucosepane:

https://www.fightaging.org/archives/2012/03/sens5-video-talking-about-ages-and-aging.php

"Advanced glycation end-products (AGEs) such as glucosepane are what you might think of as a sort of biological rust. They build up as an undesirable side-product of the chemistry of life and damage important molecular machinery in and around cells by sticking to molecules or sticking molecules together, making it impossible for them to do their jobs. The increase in AGE levels in the body with advancing age isn't a matter of straight accumulation over time - it's more dynamic than that, and the level of AGEs in the diet may play some role - but eventually it becomes enough to cause serious harm. Aging is little more than damage, and AGEs are one form of that damage.

"There are two difficulties with creating AGE-breaker drugs. Firstly, AGEs are chemical targets, not genes or proteins. Almost all of pharmaceutical research over the last 40 years has been orientated to finding drugs that interact with proteins, and with the genes that make those proteins. So we cannot call on the trillions of dollars of research and technology development that have created the modern drug industry to help us (very much - we can use some of it). Secondly, AGEs are pretty stable and tough. That is inevitable - they are in essence the physiological equivalent of the black stuff on the bottom of your baking tin - what is left after years of use and the dishwasher. (In the case of humans, 'the dishwasher' is an array of mechanisms that take care of nearly all the waste products of metabolism.) We know how to break them quite easily, but only using a process that would also dissolve every protein in your body. The trick is finding a way to cleave them and leave all the rest of you intact."

MORE COMMENTARY ON RUSSIA 2045

The Russia 2045 initiative is attracting attention from the English-language community, and here is more on that topic:

https://www.fightaging.org/archives/2012/03/more-commentary-on-russia-2045.php

"For 3 days in late February, Russian businessman Dmitry Itskov gathered 500+ futurists in Moscow for a 'Global Future 2045 Congress' - the latest manifestation of his "Russia 2045" movement. ... The occurrence of a conference like this in Russia is no big shock, of course. Russia has a huge contingent of great scientists in multiple directly Singularity-relevant areas; and it also has an impressively long history of advanced technological thinking . My dear departed friend Valentin Turchin wrote a book with Singularitarian themes in the late 1960s, and the Russian Cosmists of the early 1900s discussed technological immortality, space colonization and other futurist themes long before they became popular in the West.

"It's unclear from the online conference abstracts and other Russia 2045 materials just how much actual work is going in Russia on right now, explicitly oriented toward realizing the exciting visions Itskov describes; and it's also unclear to what extent Itskov's 'Russia 2045' movement serves an active R&D role, versus a visionary and publicity role. It appears that most of the concrete science and engineering work at the conference was presented by scientists who had made their breakthroughs outside the context of the 'Russia 2045' project; whereas Itskov and the other Russia 2045 staff were largely oriented toward high-level visioning. But of course, Russia 2045 is a new initiative, and may potentially draw more researchers into its fold as time progresses.

"Ray Kurzweil gave a fairly glowing report, noting 'It was a well funded conference, funded by a number of major corporations in Russia..... There was significant representation from the mainstream press. The ideas were taken seriously. There were people from companies, from academe, from government.... The comparison to Humanity+ or the Singularity Summit is reasonable.... The people at the conference (about 500-600) were pretty sophisticated about all the issues you and I talk and write about.'

"Clearly there are many smart scientists and engineers in Russia doing directly Singularity-relevant things; and Itskov's Russia 2045 organization seems to be doing a good job of attracting public and political attention to this work. What amount of concrete work is actually going on toward Itskov's list of grand goals is unclear to me at present, but certainly seems something to keep an eye on."

ON INDIFFERENCE TO THE FUTURE

If we judge by actions and not words, we might conclude that most people don't really care one or another when it comes to influencing the future:

https://www.fightaging.org/archives/2012/03/greeting-your-personal-future-with-indifference.php

"Someone who didn't take note of the eagerness with which people throw money at the shams, fakes, and security blankets of the 'anti-aging' marketplace might be forced to conclude that the world's inhabitants are on balance indifferent as to whether they live long or die young, whether they suffer for decades or live healthily some years down the line. There are many common sense health practices that people can undertake to maximize their remaining life expectancy and reduce the risk of age-related disease - and that's even before we start in on supporting research and development of rejuvenation biotechnology - but the majority don't do anywhere near as much as they might, and in consequence they come to suffer for it. Are we a species whose dominant trait is actually nihilism? One wonders at times.

"But the personal future of aging isn't the only thing that most people, judging by their actions, are indifferent to. We might also consider the preventable nature of well known conditions like cancer, to pick one example. Most people know that they should be exercising, they should not let themselves get fat, and they also know how to halve the risk of suffering cancer - but do they adopt the necessary changes in lifestyle? Largely no:

"More than half of all cancer is preventable, and society has the knowledge to act on this information today ... What we know [is] that lifestyle choices people make and that society can influence in a number of ways - from tobacco use to diet and exercise - play a significant role in causing cancer. Specifically, the researchers cite data demonstrating that smoking alone is responsible for a third of all cancer cases in the United States. Excess body weight and obesity account for another 20 percent."

DISCUSSION

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!

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LATEST HEADLINES FROM FIGHT AGING!

A TRANSCRIPT OF "ELIXIR OF LIFE"
Friday, March 30, 2012
https://www.fightaging.org/archives/2012/03/a-transcript-of-elixir-of-life.php
An Australian program featuring researchers Aubrey de Grey and David Sinclair: "It feels like science fiction, but it's actually true. And we're really at the cutting edge, it's a really exciting time in the field right now. ... There's no such thing as ageing gracefully. I don't meet people who want to get Alzheimer's disease, or who want to get cancer or arthritis or any of the other things that afflict the elderly. Ageing is bad for you, and we better just actually accept that. As far as I'm concerned, ageing is humanity's worst problem, by some serious distance. ... Now if you think that's an overstatement, consider this: world-wide, a hundred and fifty thousand people die each day, two-thirds of them from ageing. That means potentially one hundred thousand people could be saved every day with therapies that combat ageing. ... Ageing is simply and clearly, the accumulation of damage in the body. That's all that ageing is. What it's going to take is development of thoroughly comprehensive regenerative medicine for ageing. That means medicine which can repair the molecular and cellular damage that accumulates in our bodies throughout life, as side effects of our normal metabolic processes. ... We do not know what humanity of the future is going to want to do. If thirty or fifty years from now people don't have the problems that we thought they might have, but we didn't develop those therapies, so those people have to die anyway, after a long period of decrepitude and disease, then they're not going to be terribly happy are they? That's why we have a moral obligation to develop these technologies as soon as possible."

SEPARATING OUT THE EFFECTS OF RAPAMYCIN
Friday, March 30, 2012
https://www.fightaging.org/archives/2012/03/separating-out-the-effects-of-rapamycin.php
Via EurekAlert!: researchers have "explained how rapamycin, a drug that extends mouse lifespan, also causes insulin resistance. The researchers showed in an animal model that they could, in principle, separate the effects, which depend on inhibiting two protein complexes, mTORC1 and mTORC2, respectively. The study suggests that molecules that specifically inhibit mTORC1 may combat age-related diseases without the insulin-resistance side effect. ... The mTOR complexes, for mammalian (or mechanistic) target of rapamycin, are proteins that regulate cell growth, movement, and survival, as well as protein synthesis and transcription. Specifically, there are two mTOR complexes and one mTOR protein. The mTOR protein is the core of both complexes (mTORC1 and mTORC2), which behave differently based on their associated proteins. One or both of the mTOR complexes can be inappropriately activated in certain cancers, and dual-specific inhibitors are being developed as chemotherapeutic agents. Several theories have been put forward by researchers to explain the observations that patients receiving rapamycin are more prone to developing glucose intolerance, which can lead to diabetes. Chronic treatment with rapamycin impairs glucose metabolism and the correct functioning of insulin in mice, despite extending lifespan. The research team demonstrated that rapamycin disrupts mTORC2 in the mice, and that mTORC2 is required for the insulin-mediated suppression of glucose metabolism in the liver. On the other hand, they also demonstrated that decreasing mTORC1 signaling was sufficient to extend lifespan independently from changes in glucose metabolism. They used a mouse strain in which mTORC1 activity was decreased and saw that lifespan was extended by 14 percent, yet the animals had normal glucose metabolism and insulin sensitivity."

INVESTIGATING INTESTINAL BACTERIA AND AGING IN NEMATODES
Thursday, March 29, 2012
https://www.fightaging.org/archives/2012/03/investigating-intestinal-bacteria-and-aging-in-nematodes.php
There's a range of research to indicate that gut bacteria are important in the relationship between metabolism and aging, though the situation in higher animals is probably far more complex than in nematode worms: "A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. ... We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. ... In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases."

MORE VISCERAL FAT MEANS MORE INFLAMMATION
Thursday, March 29, 2012
https://www.fightaging.org/archives/2012/03/more-visceral-fat-means-more-inflammation.php
Yet another study showing a correlation between chronic inflammation and abdominal fat: "Obesity-related increases in multiple inflammatory markers may contribute to the persistent subclinical inflammation common with advancing age. ... We used factor analysis to identify inflammatory factor(s) and examine their associations with adiposity in older adults at risk for disability. ... [Inflammatory markers] were measured in 179 participants from the Lifestyle Interventions and Independence for Elders Pilot (Mean ± SD age 77 ± 4 years, 76% white, 70% women). Body mass index, waist circumference, and total fat mass were assessed by anthropometry and dual-energy x-ray absorptiometry. ... Greater total and abdominal adiposity are associated with higher levels of an inflammatory factor related to CRP, IL-1ra, and IL-6 in older adults, which may provide a clinically useful measure of inflammation in this population. ... [The associations were determined] after adjusting for age, gender, race/ethnicity, site, smoking, anti-inflammatory medications, comorbidity index, health-related quality of life, and physical function. These associations remained significant after further adjustment for grip strength, but only waist circumference remained associated with inflammation after adjusting for total lean mass." Waist circumference is a better correlation with the amount of visceral fat packed around the organs in comparison to body mass index.

EXCESS BODY FAT DAMAGES THE MIND
Wednesday, March 28, 2012
https://www.fightaging.org/archives/2012/03/excess-body-fat-damages-the-mind.php
There is plenty of evidence to show that being overweight for any great length of time in life causes harm, either fairly directly by boosting levels of chronic inflammation, or because that fat tissue is associated with a lack of exercise and consequent development of vascular dementia, or for a range of other possible reasons. Here is another study on this topic: "High midlife body mass index (BMI) has been linked to a greater risk of dementia in late life, but few have studied the effect of BMI across midlife on cognitive abilities and cognitive change in a dementia-free sample. ... We investigated the association between BMI, measured twice across midlife (mean age 40 and 61 years, respectively), and cognitive change in four domains across two decades in the Swedish Adoption/Twin Study of Aging. ... Latent growth curve models fitted to data from 657 non-demented participants showed that persons who were overweight/obese in early midlife had significantly lower cognitive performance across domains in late life and significantly steeper decline in perceptual speed, adjusting for cardio-metabolic factors. Both underweight and overweight/obesity in late midlife were associated with lower cognitive abilities in late life. However, the association between underweight and low cognitive abilities did not remain significant when weight decline between early and late midlife was controlled for. ... There is a negative effect on cognitive abilities later in life related to being overweight/obese across midlife. Moreover, weight decline across midlife rather than low weight in late midlife per se was associated with low cognitive abilities." The weight decline association shows up in a range of studies on weight and health; one common conclusion is that it reflects the impact that more serious medical conditions - related to weight or otherwise - can have on people.

ANALYZING THE METABOLISMS OF LONG-LIVED MICE
Wednesday, March 28, 2012
https://www.fightaging.org/archives/2012/03/analyzing-the-metabolisms-of-long-lived-mice.php
Advances in biotechnology are greatly reducing the cost of performing broad analyses of metabolism - and so researchers are gathering ever more data on the various breeds of long-lived mice that have been created in recent years: "Significant advances in understanding aging have been achieved through studying model organisms with extended healthy lifespans. Employing (1)H NMR spectroscopy, we characterized the plasma metabolic phenotype (metabotype) of three long-lived murine models: 30% dietary restricted (DR), insulin receptor substrate 1 null (Irs1(-/-)), and Ames dwarf (Prop1(df/df)). A panel of metabolic differences were generated for each model relative to their controls, and subsequently, the three long-lived models were compared to one another. Concentrations of mobile very low density lipoproteins, trimethylamine, and choline were significantly decreased in the plasma of all three models. Metabolites including glucose, choline, glycerophosphocholine, and various lipids were significantly reduced, while acetoacetate, d-3-hydroxybutyrate and trimethylamine-N-oxide levels were increased in DR compared to ad libitum fed controls. Plasma lipids and glycerophosphocholine were also decreased in Irs1(-/-) mice compared to controls, as were methionine and citrate. In contrast, high density lipoproteins and glycerophosphocholine were increased in Ames dwarf mice, as were methionine and citrate. Pairwise comparisons indicated that differences existed between the metabotypes of the different long-lived mice models. Irs1(-/-) mice, for example, had elevated glucose, acetate, acetone, and creatine but lower methionine relative to DR mice and Ames dwarfs. Our study identified several potential candidate biomarkers directionally altered across all three models that may be predictive of longevity but also identified differences in the metabolic signatures. This comparative approach suggests that the metabolic networks underlying lifespan extension may not be exactly the same for each model of longevity and is consistent with multifactorial control of the aging process."

LOWER LDL FROM AN EARLY AGE IS BETTER FOR LONG TERM HEALTH
Tuesday, March 27, 2012
https://www.fightaging.org/archives/2012/03/lower-ldl-from-an-early-age-is-better-for-long-term-health.php
Some people have an objectively better metabolism than others when it comes to longevity - perhaps better mitochondrial DNA, perhaps less LDL cholesterol, for example: "Coronary atherosclerosis - a hardening of the arteries due to a build-up of fat and cholesterol - can lead to heart attacks and other forms of coronary heart disease (CHD). Lowering low-density lipoprotein (LDL), or 'bad' cholesterol, reduces the risk of CHD ... By the time most people begin treatment to lower LDL, CHD has often been quietly developing for decades. Because coronary atherosclerosis begins early in life, lowering LDL at a younger age may produce even greater reductions in the risk of CHD. Researchers sought to test this hypothesis by using genetic data to conduct a series of 'natural' randomized controlled trials involving over one million study participants. ... researchers used a novel study design called a Mendelian randomized controlled trial (mRCT) to study the effect of nine single-nucleotide polymorphisms (SNPs), or single-letter changes in DNA sequence, each of which is associated with lower levels of LDL cholesterol. Because each of these SNPs is allocated randomly at the time of conception, inheriting one of these SNPs is like being randomly allocated to a treatment that lowers LDL cholesterol beginning at birth. The researchers found that all nine SNPs were associated with a consistent 50-60 percent reduction in the risk of CHD for each 1 mmol/L (38.67 mg/dl) lower lifetime exposure to LDL cholesterol. "

CD47 AS A POTENTIAL TARGET FOR MANY CANCERS
Tuesday, March 27, 2012
https://www.fightaging.org/archives/2012/03/cd47-as-a-potential-target-for-many-cancers.php
Commonalities between many different forms of cancers will become increasingly important as biotechnology offers the ability to target them. They offer the prospect of a simplifying of cancer research and development, and far more cost-effective therapies - the big question is to what degree they exist at all: "A decade ago, biologist Irving Weissman [discovered] that leukemia cells produce higher levels of a protein called CD47 than do healthy cells. CD47, he and other scientists found, is also displayed on healthy blood cells; it's a marker that blocks the immune system from destroying them as they circulate. Cancers take advantage of this flag to trick the immune system into ignoring them. In the past few years, Weissman's lab showed that blocking CD47 with an antibody cured some cases of lymphomas and leukemias in mice by stimulating the immune system to recognize the cancer cells as invaders. Now, he and colleagues have shown that the CD47-blocking antibody may have a far wider impact than just blood cancers. ... What we've shown is that CD47 isn't just important on leukemias and lymphomas. It's on every single human primary tumor that we tested. ... Moreover, Weissman's lab found that cancer cells always had higher levels of CD47 than did healthy cells. How much CD47 a tumor made could predict the survival odds of a patient. ... To determine whether blocking CD47 was beneficial, the scientists exposed tumor cells to macrophages, a type of immune cell, and anti-CD47 molecules in petri dishes. Without the drug, the macrophages ignored the cancerous cells. But when the CD47 was present, the macrophages engulfed and destroyed cancer cells from all tumor types. Next, the team transplanted human tumors into the feet of mice, where tumors can be easily monitored. When they treated the rodents with anti-CD47, the tumors shrank and did not spread to the rest of the body. In mice given human bladder cancer tumors, for example, 10 of 10 untreated mice had cancer that spread to their lymph nodes. Only one of 10 mice treated with anti-CD47 had a lymph node with signs of cancer. Moreover, the implanted tumor often got smaller after treatment."

A REPORT ON HAIR REPIGMENTATION
Monday, March 26, 2012
https://www.fightaging.org/archives/2012/03/a-report-on-hair-repigmentation.php
Hair color - and loss - is one of the aspects of aging that people care about too much in comparison to its effects on health. There are far more important degenerations to consider. Nonetheless, here is a report suggesting that better control over the cell signaling could restore lost hair color by directing pigment cells to get back to work: "We report the first case of progressive hair repigmentation associated with the use of lenalidomide in an elderly patient with multiple myeloma. The influence of lenalidomide on follicular melanogenesis may involve removing the inhibitory influences of some cytokines such as IL-1, IL-6 and TNF-α. In addition, certain endocrine effects of lenalidomide on the hypophyseal-adrenal axis could explain its action on hair pigmentation. We further hypothesize that lenalidomide may be capable of stimulating migration and/or differentiation of melanocytes to promote repigmentation of gray hair follicles. Pending the clarification of how hair repigmentation occurs with lenalidomide, our observation materializes the concept that hair graying may not be an irreversible process." This sort of brute force approach is, however, far less desirable than working to fix the underlying levels of cellular damage that lead to changed signaling and the decline of melanocyte activity in the first place.

AGE HAS LITTLE IMPACT ON THE VIABILITY OF A DONOR KIDNEY
Monday, March 26, 2012
https://www.fightaging.org/archives/2012/03/age-has-little-impact-on-the-viability-of-a-donor-kidney.php
This research should be added to that showing that failure of systems in the body, such as stem cells, is as much a consequence of the overall bodily environment and the biochemical signals it generates as it is damage to the systems specifically: "People with kidney failure may think that they're better off getting a new kidney from a young and spry donor, but a recent study indicates that for those over 39 years old, the age of a live donor - ranging from 18 to 64 years - has an insignificant effect on the long-term health of a transplanted kidney. ... [Researchers] analyzed the survival of kidneys from donors of different age groups that were transplanted into recipients of different age groups. Their study included data from all adult kidney transplants from living donors that were performed in the United States from January 1988 to December 2003, with follow-up through September 2007. With the exception of recipients aged 18 to 39 years, who benefited the most when they received kidneys from donors aged 18 to 39 years, donor age between 18 and 64 years had minimal effect on the survival of transplanted kidneys. ... many patients will likely find that participating in living donor paired exchanges - and possibly receiving a kidney from an older-aged donor - is a better option than continuing to wait for a deceased donor transplant."

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