Fight Aging! Newsletter, February 28th 2011

FIGHT AGING! NEWSLETTER
February 28th 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- Resveratrol is Weak Medicine, and It's Well Past Time to Move On
- Launch of the International Aging Research Portfolio
- Photography: Russian Cryonics, American Rejuvenation Biotechnology
- The New Stem Cell Science of Progeria
- Discussion
- Latest Headlines from Fight Aging!

RESVERATROL IS WEAK MEDICINE, AND IT'S WELL PAST TIME TO MOVE ON

I have long argued that the research and development community is largely working on ineffective paths when it comes to greatly enhanced human longevity in our lifetimes. The dominant public focus on largely useless outputs like resveratrol is one symptom of this problem:

https://www.fightaging.org/archives/2011/02/resveratrol-is-weak-medicine-and-its-well-past-time-to-move-on.php

"There is a very simple measure for any new potential therapy for enhanced longevity: is it either (a) doing at least as well as calorie restriction in mice when it comes to health and longevity, or (b) achieving important results that calorie restriction cannot show in mice - such as outright rejuvenation. The popular supplement resveratrol fails miserably to achieve significant results in either of these goals after more than five years of experimentation and hundreds of millions of dollars in research funding. This means that it is a dead end, or so close to one as makes no real difference. The only value gained lies in incremental improvements in the understanding of metabolism - which could have been achieved while studying more effective paths to the same end goal.

"Whenever a new supplement, drug, or something else you can put in your mouth is announced to possibly affect longevity, there follows a breathless wave of hype and money-making. Go search [on Google] for 'resveratrol' to see the present pointless wasteland of thoughtless buyers and manipulative sellers. You'd think that no-one has a memory of longer than a year: every time this happens exactly the same way, and in the end it all comes to nothing.

"Silver bullets don't exist, and the future of longevity science will not be found in paths that fail to show immediate, exciting benefit in mouse studies. When there are multiple ways to extend mouse life span by 50%, why would anyone be worked up about about something that fails to move the needle at all? It's way past time to move on from the resveratrols of the world and focus on research and development that can have a positive effect on the future of human longevity."

The path I favor is, of course, is largely outlined by the Strategies of Engineered Negligible Senescence and similar repair-focused research programs:

https://www.fightaging.org/archives/2004/11/strategies-for-engineered-negligible-senescence.php
https://www.fightaging.org/archives/2006/11/the-engineers-viewpoint-treat-change-as-damage.php

LAUNCH OF THE INTERNATIONAL AGING RESEARCH PORTFOLIO

The International Aging Research Portfolio tracks aging research work around the world, providing an extensive database of publicly funded projects from the last decade and a half, and a selection of tools to mine that data:

https://www.fightaging.org/archives/2011/02/the-international-aging-research-portfolio-launches.php

"If you are a statistics addict, this might keep you occupied for a while. The aggregated funding data and trends in research are particularly interesting, and could be more so if further sliced and diced. For example, funding by theory of aging. ... Color me surprised that funding of work on telomeres in aging is so very far ahead [of work focused on other theories of aging] - but there's the purpose of data mining, to learn. The hope here is that data mining tools that operate on this large data set will provide compelling benefits for the research community, such as by making it easier to match up research proposals to funding sources based on the sort of awards made in the past."

PHOTOGRAPHY: RUSSIAN CRYONICS, AMERICAN REJUVENATION BIOTECHNOLOGY

Links to recent photograph from either side of the old divide:

https://www.fightaging.org/archives/2011/02/photographs-russian-cryonics-american-rejuvenation-biotechnology.php

"KrioRus and the SENS Foundation are two amongst a wide range of modern ventures in longevity science - although very different in focus, both are just a few years old and spring from overlapping communities of supporters, most of whom have been involved in the space for a decade or two at most."

THE NEW STEM CELL SCIENCE OF PROGERIA

As the tools and techniques of biotechnology advance, they afford ever greater insight into the accelerated aging condition of progeria - and also answer the question of whether a working therapy would also be of some benefit to the rest of us:

https://www.fightaging.org/archives/2011/02/the-new-stem-cell-science-of-progeria.php

"Application of the comparatively recent technologies of induced pluripotency (used to produce induced pluripotent stem cells, or iPS cells) are leading to further discoveries in both aberrant and 'normal' aging ... Compared to normal skin fibroblasts, cells from Progeria patients have misshapen nuclei and a range of other nuclear defects, including a disorganized nuclear lamina, loss of super-condensed DNA, telomere shortening and genomic instability. Yet, despite their 'old' appearance and characteristics, these cells could be readily converted into iPS cells. ... The reprogramming process erased all nuclear and epigenetic defects and the rejuvenated pluripotent cells looked and acted like perfectly normal healthy cells."

You might compare that interesting result with a demonstration from late last year of the effects of reprogramming on cells suffering from mitochondrial damage:

https://www.fightaging.org/archives/2010/12/mitochondrial-rejuvenation-via-induced-pluripotency-techniques.php

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!

IMPROVED MANIPULATION OF THE IMMUNE SYSTEM
Friday, February 25, 2011
https://www.fightaging.org/archives/2011/02/improved-manipulation-of-the-immune-system.php
Can improving the technologies of vaccination lead to gains in the capacity of the age-damaged immune system? Progress in the ability to manipulate the immune system may pay off in unexpected ways when further technologies are built atop a new platform: "Vaccine scientists say their 'Holy Grail' is to stimulate immunity that lasts for a lifetime. Live viral vaccines such as the smallpox or yellow fever vaccines provide immune protection that lasts several decades, but despite their success, scientists have remained in the dark as to how they induce such long lasting immunity. Scientists [have] designed tiny nanoparticles that resemble viruses in size and immunological composition and that induce lifelong immunity in mice. They designed the particles to mimic the immune‑stimulating effects of one of the most successful vaccines ever developed - the yellow fever vaccine. The particles, made of biodegradable polymers, have components that activate two different parts of the innate immune system and can be used interchangeably with material from many different bacteria or viruses. ... the yellow fever vaccine stimulated multiple Toll‑like receptors (TLRs) in the innate immune system. TLRs [are] molecules expressed by cells that can sense bits of viruses, bacteria and parasites ... the immune system sensed the yellow fever vaccine via multiple TLRs, and that this was required for the immunity induced by the vaccine. ... We found that to get the best immune response, you need to hit more than one kind of Toll‑like receptor. Our aim was to create a synthetic particle that accomplishes this task. ... In experiments with monkeys, nanoparticles with viral protein could induce robust responses greater than five times the response induced by a dose of the same viral protein given by itself, without the nanoparticles."

AN EXAMPLE OF YOUTHFUL REGENERATION
Friday, February 25, 2011
https://www.fightaging.org/archives/2011/02/an-example-of-youthful-regeneration.php
Young mammals are capable of feats of regeneration: even in humans, it has been known for young children to regenerate lost fingertips. That capacity fades with age, however. Researchers are investigating the biochemistry of this behavior for much the same reasons as they look at regenerating species such as salamanders - if the capacity is there, perhaps it can be restored in adults. "Researchers, working with mice, found that a portion of the heart removed during the first week after birth grew back wholly and correctly - as if nothing had happened. ... This is an important step in our search for a cure for heart disease, the No. 1 killer in the developed world. We found that the heart of newborn mammals can fix itself; it just forgets how as it gets older. The challenge now is to find a way to remind the adult heart how to fix itself again. ... Previous research has demonstrated that the lower organisms, like some fish and amphibians, that can regrow fins and tails, can also regrow portions of their hearts after injury. ... In contrast, the hearts of adult mammals lack the ability to regrow lost or damaged tissue, and as a result, when the heart is injured, for example after a heart attack, it gets weaker, which eventually leads to heart failure. ... The researchers found that within three weeks of removing 15 percent of the newborn mouse heart, the heart was able to completely grow back the lost tissue, and as a result looked and functioned just like a normal heart. The researchers believe that uninjured beating heart cells, called cardiomyocytes, are a major source of the new cells. They stop beating long enough to divide and provide the heart with fresh cardiomyocytes."

DNA METHYLATION CORRELATES WITH AGE-RELATED FRAILTY
Thursday, February 24, 2011
https://www.fightaging.org/archives/2011/02/dna-methylation-correlates-with-age-related-frailty.php
We expect to see good correlations between many aspects of our biology and aging: "Epigenetic variations have been widely described to occur during the aging process. To verify if these modifications are correlated with the inter-individual phenotypic variability of elderly people, we searched for a correlation between global DNA methylation levels and frailty. We found that the global DNA methylation levels were correlated to the frailty status in middle/advanced-aged subjects but not with age. A 7-year follow-up study also revealed that a worsening in the frailty status was associated to a significant decrease in the global DNA methylation levels. These results suggest that the relaxation of the epigenetic control in aging is specifically associated with the functional decline rather than with the chronological age of individuals. Thus, the modifications of DNA methylation, representing a drawbridge between the genetic and the environmental factors affecting the age-related decay of the organism, may play an important role in determining physiological changes over old age." Equally, it may go the other way - these changes could just as well be the symptoms of damaged systems flailing as they try to adapt to countless small breakages at the level of cells and molecular machinery. It is important in the development of therapies for aging to try to identify the root causes, as fixing those will also solve secondary issues.

DECELLULARIZATION TO CREATE BLOOD VESSELS FOR TRANSPLANT
Thursday, February 24, 2011
https://www.fightaging.org/archives/2011/02/decellularization-to-create-blood-vessels-for-transplant.php
Decellularization is proving to be a versatile technology in tissue engineering: grow the tissue from stem cells or accept a donor organ, strip its cells to leave behind the extracellular matrix, and then repopulate it from the recipient's stem cells to make it ready for transplant. For example: "Heart bypass patients may soon be able to get new arteries without having to sacrifice vessels from other parts of their body, thanks to ready-made, off-the-shelf artificial blood vessels. Biomedical engineers have been trying to build replacement blood vessels, needed for coronary artery bypass surgery and kidney dialysis patients, for three decades. Researchers from Humacyte Inc., in Durham, N.C., discovered the trick: recruiting cells to build the vessel, then washing them away so the nonliving tissue is storable and works for anyone. ... The company has managed to make a "universal blood vessel. This is very practical and convenient for clinical applications. ... Other approaches, customized with a patient's own cells, take several months to prepare. ... Though Humacyte is starting to plan human clinical trials, it's too early to predict when the grafts would become available to the general public. ... [researchers] not yet know how much the grafts would cost, but anticipates it will be less than the $15,000-and-up for personalized grafts from patient's own cells. The company can use cells from multiple cadavers to generate hundreds of grafts at once, making production much cheaper."

EXERCISE VERSUS ACCELERATED MITOCHONDRIAL DYSFUNCTION
Wednesday, February 23, 2011
https://www.fightaging.org/archives/2011/02/exercise-versus-accelerated-mitochondrial-dysfunction.php
Researchers demonstrate that exercise can counter some of the effects of an engineered acceleration of mitochondrial dysfunction: "researchers [found] that signs of premature aging were halted - and even reversed - in virtually every tissue and organ in the bodies of exercised mice. Mice genetically altered to age faster were forced to run on treadmills for 45 minutes, three times a week. Five months later, the mice looked as young, healthy and active as wild-type mice - mice that didn't have the genetic mutation - while their sedentary and same-aged siblings were balding, greying and shrinking. .. The mice were genetically manipulated to age twice as fast as normal because of a defect in the repair system of their mitochondria, the powerhouses or furnaces inside each cell that give our body energy. Evidence has been mounting for decades that the older we get, the more mutations we accumulate in mitochondrial DNA. The furnaces start to break down, resulting in a steady decline in tissue and organ function. ... In our study, we saw huge recovery in mitochondrial function [in] the exercised mice." We might expect this result, given that exercise is known to have an impact on longevity, as well as on many of the biological mechanisms that are associated with aging. Given the importance of mitochondria in aging, it is interesting to see more work on the links between exercise and their function - but we must always be careful when evaluating work based on engineered dysfunction or accelerated aging. It is often the case that the putative end result has little relevance to "normal" aging.

THEORIZING ON THRIFTY GENES AND OVERNUTRITION
Wednesday, February 23, 2011
https://www.fightaging.org/archives/2011/02/theorizing-on-thrifty-genes-and-overnutrition.php
An open access paper: "Nearly 50 years ago geneticist James Neel famously proposed that 'thrifty genes' were important contributors to the rising prevalence of diabetes. Such genes promote efficient use and conservation of food energy, he theorized, and thus were favored by natural selection to help our ancient ancestors cope with famines. Now widespread in various populations, they predispose to obesity and diabetes, abetting a tendency to prepare for famines that never come. ... Here I propose an extension of this reproduction-centered version of Neel's theory that bears on aging. One of my key premises is that many windows of opportunity for reproductive booms occurred during the Holocene as agricultural innovations spread, periodically increasing food availability between times of nutritional stress. The periods of plenty selected for genotypes capable of rapidly ramping up fecundity as food intake increased. ... I believe the boom times' selection of genotypes prone to nutrition-cued accelerated development is having an especially problematic effect today because of widespread childhood overnutrition. Accelerated development, which enhanced reproductive success in the past, now has a pro-aging effect with rapidly growing costs. Indeed, when viewed through the lens of the antagonistic pleiotropy theory of aging, this effect seems anything but thrifty: It predisposes toward what might be called the spendthrift phenotype, characterized by chronic activation of pro-growth pathways - notably those involving mTOR, insulin, and insulin-like growth factor-1 - that support rapid development and sexual maturation but that also underlie later senescence. The modern fallout encompasses a much broader array of age-associated ills than the diabetes that prompted Neel's original hypothesis. Indeed, the spendthrift phenotype may well increase the age-associated risks of most if not all diseases of aging, like the ruinous adult legacy of flush, fast-living youth."

CRYONICS MAGAZINE IS LOOKING GOOD
Tuesday, February 22, 2011
https://www.fightaging.org/archives/2011/02/cryonics-magazine-is-looking-good.php
The Cryonics magazine published by Alcor is looking very professionally done these days. If you head on over there, you'll find a good-looking website and crisp PDF downloads: "Cryonics magazine is the quarterly electronic publication of the Alcor Life Extension Foundation. Cryonics magazine is also available as a paper magazine by ordering individual copies at MagCloud or by ordering subscriptions to the paper edition from Alcor. The magazine website also publishes exclusive content and news items that are relevant to the science and practice of cryonics. ...The 2010 4th quarter issue of Cryonics covers the challenging and sensitive topic of persuading family members to make cryonics arrangements. Editor Aschwin de Wolf contributes an article about writing cryonics case reports and how to overcome the challenges that a growing cryonics organization presents for writing them. We continue our coverage of Alcor staff members with a feature on Alcor Finance Director Bonnie Magee. ... The 2010 3rd quarter issue of Cryonics publishes the first comprehensive Alcor Human Cryopreservation Protocol. This document covers all steps of cryonics procedures, from standby to long term care at liquid nitrogen temperatures. Robert Freitas summarizes his econometric analysis of Alcor finances and Alcor staff member and life extension historian Mike Perry is featured in this issue's member profile."

TOWARDS RAPID PRINTING OF HUMAN SKIN
Tuesday, February 22, 2011
https://www.fightaging.org/archives/2011/02/towards-rapid-printing-of-human-skin.php
From CNN: "We started out by taking a typical desktop inkjet cartridge. Instead of ink we use cells, which are placed in the cartridge ... The device could be used to rebuild damaged or burned skin. The project is in pre-clinical phases and may take another five years of development before it is ready to be used on human burn victims. ... researchers say organs - not just skin - could be printed using similar techniques. ... The skin-printing process involves several steps. First, a small piece of skin is taken from the patient. The sample is about half the size of a postage stamp, and it is taken from the patient by using a chemical solution. Those cells are then separated and replicated on their own in a specialized environment that catalyzes this cell development. ... We expand the cells in large quantities. Once we make those new cells, the next step is to put the cells in the printer, on a cartridge, and print on the patient ...The printer is then placed over the wound at a distance so that it doesn't touch the burn victim. ... It's like a flat-bed scanner that moves back and forth and put cells on you. ... The device can fabricate healthy skin in anywhere from minutes to a few hours, depending on the size and type of burn. ... researchers said they're pleased with results of preliminary laboratory testing with the skin printer [and] already have been able to [make] healthy skin."

COGNITIVE AGING AS A DISEASE
Monday, February 21, 2011
https://www.fightaging.org/archives/2011/02/cognitive-aging-as-a-disease.php
There is a debate over whether aging is a disease, and here is some insight into where the aging of the brain and neurodegenerative diseases fit into that larger argument: the "question of whether 'aging itself' is or is not a 'disease' has long been mooted in biogerontological circles, with a long-held rhetorical preference for asserting that it is not, but rather, that it is a risk factor for the specific diseases of aging. By contrast, the same fundamental semantic dispute was initially resolved in the opposite direction with regard to age-related cognitive decline and dementia, beginning in the early decades after Alois Alzheimer and Emil Kraepelin first identified the pathological basis of the Alzheimer's disease (AD) until the early 1970s. For most of the twentieth century, it was held that dementia occurring in younger people should be classified as a disease, whereas dementia should be expected and accepted when it occurred in people at more advanced ages, despite the knowledge that the lesions linked to Alzheimer's dementia accumulated throughout the course of "normal" aging in middle age and onward, and that the pathological basis of the disorder was the same in both cases. ... But beginning in the 1960s, a loose alliance led by social gerontologists but quickly coming to include biogerontologists, geriatricians, and patient advocacy groups successfully campaigned for a new understanding: that while some level of minor cognitive decline was indeed a 'normal' and inevitable part of aging, the newly-rediscovered clinicopathological entity, 'Alzheimer's disease,' was exactly that: a disease, against which the full force of public and private biomedical research should be mobilized in the pursuit of a cure." These debates are almost entirely driven by the state of regulation in medical development; in particular that the FDA does not approve treatments that are not aimed at a defined and accepted disease - and aging is not a disease to the regulators, so no-one can try to treat it legally. This is an abysmally stupid situation, but sadly par for the course wherever government becomes involved.

THE SHAPE OF AGING
Monday, February 21, 2011
https://www.fightaging.org/archives/2011/02/the-shape-of-aging.php
An interesting piece on the comparison of aging between species: "The 'shape' of aging describes how much mortality, the risk of dying, changes with age. One way of measuring the shape of aging is the 'aging factor' across species. For example, the common swift has an aging factor of 2, meaning mortality doubles during its adult life, compared with modern humans, who have an aging factor that exceeds 2000. ... Some organisms live a short time, others live a long time. This is the pace of ageing. Short-lived species have a fast pace of ageing, and long-lived species have a slow pace of ageing. Pace describes how quickly the clock of life ticks away. For humans it ticks slowly, for small songbirds like the robin it ticks very fast. At the age of 15, only 2 out of 100,000 girls in Sweden die, but one out of every two women aged 110 will die. This large difference in mortality at the beginning and end of adult life means that for humans the shape of ageing is steep, whereas in other species like the common swift it is shallow. And in some species the risk of death can even fall with age, with older individuals having the least risk of dying. This seems to be the case for the desert tortoise, and for alligators or crocodiles. ... Comparing robins with Swedish women, humans have a slow pace of ageing whereas the robin's is fast, so in terms of length of life the humans are doing best. But if we look at the impact ageing has on death rate the robin wins. Its shape of ageing is fairly flat whereas the humans' is steep, indicating that death rates increase markedly with age ... Not all species with short lives live fast and die young. Robins do, but mountain sheep do things differently. They also live pretty fast but die older. From the data I have, it seems that live fast die young is only one option; you can also live fast and die older, or live slower and die young, or live slow and die old. There might be every combination in nature. That's something we need to find out in the future with better data."

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