Fight Aging! Newsletter, August 13th 2012

August 13th 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!



- Ultimately, Self-Interest Will Emerge as a Driving Force
- Replacement Parts: Xenotransplantion Versus Organ Engineering
- Regrowing the Esophageal Lining
- Contemplating the Causes of Immunosenescence
- Discussion
- Latest Headlines from Fight Aging!
    - Proposing a Hyperfunction Theory of Aging
    - Towards a Blood Test for Alzheimer's Disease
    - Looking for Longevity-Related MicroRNAs in Centenarians
    - On Oxidative Stress and NAD+ Metabolism in Aging
    - Cosmism and Views of Radical Life Extension
    - A Terrible Reason to Oppose Healthy Life Extension
    - A Therapeutic Target for Dry Macular Degeneration
    - Eurosymposium on Healthy Aging Announced
    - Plan to Live for Longer than You Think You Will
    - On Intermittent Fasting


Self-interest is a potent thing, especially when it comes to retaining one's health and life in the face of threats to both:

"At the present time two groups of people well placed to influence progress in rejuvenation biotechnology are, for the most part, acting against their own self-interest. It is generally the case that such situations do not last: self-interest wins out in the long term.

"On the one hand we have the world's high net worth individuals, most of whom do very little in the way of funding research into aging or the conditions of aging. It is their inaction that is opposed to their own self-interest: they are all aging to death at the same pace as the rest of us, after all. When it comes to access to medical technology the world is remarkably flat: the poor struggle in this as in everything else, but the wealthy have no more ability to buy a way out of aging (or heart disease, or cancer, or any of the other conditions that attend aging) right this instant than does anyone else. What they do have is a far greater ability to create a near future in which rejuvenation biotechnologies exist and are just as widely available as any present day clinical procedure.

"It is in the self-interest of everyone who can significantly speed up the development of ways to reverse aging to set forth and do exactly that - but very few are making the effort. At some point it will become evident to the public and the world at large that aging to death whilst surrounding by wealth is insanity in an age in which those resources could be used for the development of age-reversing medicine: ways to repair mitochondrial DNA, break down accumulated metabolic byproducts that clog up cells, clear out senescent cells, restore declining stem cell activity, and so forth. But as yet this is not obvious enough to those people who matter.

"The second group acting against their own self-interest in the matter of rejuvenation biotechnology are those researchers who could be working on relevant scientific projects but are not. Much of the aging research community doesn't in fact do any more than study aging, and the minority who do work on development of therapies are largely investigating the slow and unproductive path of slowing aging via metabolic manipulation. A far better road exists: the pursuit of ways to repair the damage that causes aging, as outlined by the SENS Foundation but by no means limited to their chosen methods of implementation. Work on the repair of aging is far more likely to produce radical advances in medicine worthy of this age of accelerating progress: ways to restore the old to vigor and greatly extend health human life. Researchers who are not working on something that looks a lot like SENS are locking themselves out of the most interesting and most valuable room in the house.

"But as I said above, self-interest tends to win out in the long run. As more attention is given to SENS, longevity science, and the repair of aging, it becomes ever more likely it is that self-interest will emerge as a driving force in funding and research."


A recent article looks at competition between two lines of research, both aimed at building replacement organs that are matched to a patient's own tissues:

"Faced with this common problem, Vacanti and Cooper have championed very different solutions. Cooper thinks that the best hope of providing more organs lies in xenotransplantation - the act of replacing a human organ with an animal one. From his time in Cape Town to his current position at the University of Pittsburgh, he has been trying to solve the many problems that occur when pig organs enter human bodies, from immune rejection to blood clots. Vacanti, now at Massachusetts General Hospital, has instead been developing technology to create genetically tailored organs out of a patient's own cells, abolishing compatibility issues. 'I said to myself: why can't we just make an organ?' he recalls.

"In the race to solve the organ shortage, xenotransplantation is like the slow and steady tortoise, still taking small steps after a long run-up, while organ engineering is more like a sprinting hare, racing towards a still-distant finish line. Most of those betting on the race are backing the hare. Industry support has dried up for xenotransplantation after years of slow progress, leaving public funders to pick up the expensive tab. Stem cells, meanwhile, continue to draw attention and investment. But both fields have made important advances in recent years, and the likely winner of their race - or whether it will result in a draw - is far from clear."


Here is an example of the present current cutting edge of tissue engineering in practice - using decellarized animal tissues and producing better results than more traditional methods of reconstructive surgery:

"The scaffolding is 'extracellular matrix,' or ECM - a matrix or tissue framework developed from pig tissue from which all the pig's cells have been removed. The ECM naturally contains growth factors and proteins among other molecules that appear to signal the recipient's adult stem cells, and possibly other cells, to transform themselves into site-specific cells needed at that particular location of the body. ... For the right candidate for the surgery, Dr. Jobe cuts the cylindrical tube of lining at either end of the damaged area [of the esophagus], as if he were removing a damaged piece of pipe, before pulling it out of the throat in a way similar to taking off a tube sock. If nothing else were done, resultant scarring would prevent swallowing and clog the throat. The ECM process regenerates healthy tissue without scarring.

"Next Dr. Jobe uses pig ECM that Dr. Badylak developed and now produced commercially to form a new esophageal lining. The ECM tube is soaked until it is flaccid and then slipped over a collapsed spring-like stent. Once in place, the stent is expanded until it presses the ECM against the esophageal wall where the lining had been removed. In a process known as wallpapering, the stent holds the ECM in place until it adheres to the wall. In a matter of days the ECM fully attaches to the esophagus wall to serve as a framework for stem cells or other cells to migrate there and heed signals from the ECM or from neighboring esophagus cells to transform into esophageal lining. Soon after the surgery with the stent in place, the patient can consume liquids. Full replacement of the lining occurs within several weeks. In time, the pig ECM is replaced naturally with human tissue."


The immune system fails in characteristic ways with aging, entering a state known as immunosenescence in which it causes chronic inflammation and fails to protect against pathogens or destroy unwanted cells. The immune system fails faster for some people than others, however. Here researchers propose that infection with cytomegalovirus (CMV) in youth leads to a faster decline in the immune system in older years, and thus have a lot to do with differences in aging between populations:

"Is immunosenescence an intrinsic ageing process leading to dysregulation of immunity or an adaptive response of the individual to pathogen exposure? Age-associated differences in bone marrow immune cell output and thymic involution suggest the former. Accepted hallmarks of immunosenescence (decreased numbers and percentages of peripheral naïve T cells, especially CD8+ cells, and accumulations of memory T cells, especially late-stage differentiated CD8+ cells) suggest the latter, viewed as the result of depletion of the reservoir of naïve cells over time by contact with pathogens and their conversion to memory cells, the basis of adaptive immunity."

"One very striking difference [between industrialized Western populations and those of poorer regions is that in] the 'wild-type' situation, all humans are infected with CMV from the age of ca. 2 months on, when they no longer receive only anti-CMV antibody in the mother's milk, but also the infectious virus that has reactivated in the meantime. CMV-negativity is an artifact of civilization, hygiene and decreased breast feeding. Hence, in our pilot study of young and old men in rural Pakistan, all the young were already CMV-positive. As 'old' is viewed as [greater than] 50 years in this society, we sought to establish whether age-associated differences in immune phenotypes that we and others had established in older European and US populations were similar in Pakistanis, and whether they manifested earlier in the latter.

"We concluded that there were two major differences between the Pakistani population and the historical controls of [subjects from Western, industrialized regions]. One was that we did indeed see age-associated differences in CD8+ T cells earlier in the Pakistanis, and the other was that we saw for the first time in a healthy population that not only the CD8+ subset but also the CD4 + T cells were affected. This we had otherwise only seen in pathological European populations, eg. those with Alzheimer's. We interpret this to mean that the level of 'antigenic stress' in the Pakistani population, old at 50, could indeed be leading to 'premature immunosenescence'."

You'll find more on cytomegalovirus as a cause of immune system decline back in the Fight Aging! archives. One possible treatment would involve targeting and destroying the memory T cells devoted to CMV, thus freeing up space for other immune cells that focus on destroying threats:


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, August 10, 2012
There are a great many theories of aging, and here is another for the pile from a researcher who leans towards aging as genetic programming rather than aging as accumulated damage: "The biological mechanisms at the heart of the aging process are a long-standing mystery. An influential theory has it that aging is the result of an accumulation of molecular damage, caused in particular by reactive oxygen species (ROS) produced by mitochondria. This theory also predicts that processes that protect against oxidative damage (involving detoxification, repair and turnover) protect against aging and increase lifespan. ... However, recent tests of the oxidative damage theory, many using the short-lived nematode worm Caenorhabditis elegans, have often failed to support the theory. This motivates consideration of alternative models. One new theory [proposes] that aging is caused by hyperfunction, i.e. over-activity during adulthood of processes (particularly biosynthetic) that contribute to development and reproduction. Such hyperfunction can lead to hypertrophy-associated pathologies, which cause the age increase in mortality. ... Here we assess whether the hyperfunction theory is at all consistent with what is know about C. elegans aging, and conclude that it is. In particular, during adulthood C. elegans show a number of changes that may reflect pathology and/or hyperfunction. Such changes seem to contribute to mortality, at least in some cases (e.g. yolk accumulation). ... Our assessment suggests that the hyperfunction theory is a plausible alternative to the molecular damage theory to explain aging in C. elegans."

Friday, August 10, 2012
Progress towards a non-invasive test for Alzheimer's disease: "Reliability and failure to replicate initial results have been the biggest challenge in this field. We demonstrate here that it is possible to show consistent findings. ... [Researchers] measured the levels of 190 proteins in the blood of 600 study participants [including] healthy volunteers and those who had been diagnosed with Alzheimer's disease or mild cognitive impairment (MCI). MCI, often considered a harbinger for Alzheimer's disease, causes a slight but measurable decline in cognitive abilities. A subset of the 190 protein levels (17) were significantly different in people with MCI or Alzheimer's. When those markers were checked against data from 566 people participating in the multicenter Alzheimer's Disease Neuroimaging Initiative, only four markers remained: apolipoprotein E, B-type natriuretic peptide, C-reactive protein and pancreatic polypeptide. Changes in levels of these four proteins in blood also correlated with measurements from the same patients of the levels of proteins [beta-amyloid] in cerebrospinal fluid that previously have been connected with Alzheimer's. The analysis grouped together people with MCI, who are at high risk of developing Alzheimer's, and full Alzheimer's. ... Though a blood test to identify underlying Alzheimer's disease is not quite ready for prime time given today's technology, we now have identified ways to make sure that a test will be reliable."

Thursday, August 9, 2012
Efforts continue to correlate longevity with the activity levels of specific genes: "MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. ... We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. ... we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA.

Thursday, August 9, 2012
NAD+ is featured in the energy generation cycle that takes place in mitochondria within cells, as well as many other roles. Its levels appear to influence and be influenced by all sorts of mechanisms related to longevity and aging. "Nicotinamide adenine dinucleotide (NAD+) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD+ also represents the sole substrate for the nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP) and the sirtuin family of NAD-dependent histone deacetylases. Age associated increases in oxidative nuclear damage have been associated with PARP-mediated NAD+ depletion and loss of SIRT1 activity in rodents. In this study, we further investigated whether these same associations were present in aging human tissue. Human pelvic skin samples were obtained from consenting patients aged between 15-77 and newborn babies (0-1 year old) ... DNA damage correlated strongly with age in both males and females whereas lipid oxidation (MDA) levels increased with age in males but not females. PARP activity significantly increased with age in males and inversely correlated with tissue NAD+ levels. These associations were less evident in females. A strong negative correlation was observed between NAD+ levels and age in both males and females. SIRT1 activity also negatively correlated with age in males but not in females. Strong positive correlations were also observed between lipid peroxidation and DNA damage, and PARP activity and NAD+ levels in post pubescent males. This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD+ catabolism in human tissue. The resulting NAD+ depletion may play a major role in the aging process, by limiting energy production, DNA repair and genomic signalling."

Wednesday, August 8, 2012
A piece on the continuing tradition of Russian cosmism, influential on the transhumanist movement and the modern community that advocates for radical life extension through biotechnology: "According to Dr. Igor Vishev (b. 1933), a distinguished Russian scientist and philosopher, it is likely that there are people alive today who will never die. Just stop for a moment and think about that. Alive today. Never die. ... Vishev's line of thought is a 21st-century variation of Russian cosmism, a philosophical tendency that started with the eccentric 19th-century librarian and thinker Nikolai Fedorov (1829-1903) and continued through the 20th century ... Vishev is convinced that medical technology is advancing so rapidly that sometime later in this century, Homo sapiens will become Homo immortalis. He believes that our current lifespan of up to 90 or, in extreme instances, slightly over 100 years, is not cast in stone or fixed in nature but an evolutionary stage out of which we are now emerging. Genetic engineering, replacement of natural organs with artificial instruments, nanotechnology, and other developing technologies could now extend our lives well beyond today's assumed limits. He proposes that a 200-year-old person is a present possibility, and a person who could live at least as long as a 2,000-year-old redwood tree is certainly imaginable. Such longevity will be self-propelling. New discoveries during the 200-year (or 2,000-year) lifespan would make what Vishev calls 'practical immortality' a fairly safe bet. By 'practical' he means 'realizable' but not absolute. People could still die, accidentally or otherwise, but eventually techniques of 'practical resurrection,' toward which today's cloning is a primitive first step, would be able to restore life to those who somehow lose it. Vishev's philosophy, which he calls 'practical immortology,' is an attempt to shift our entire culture and worldview from one based on the certainty of human mortality to one based on the prospect of human immortality. This shift requires radical new directions not only in science and technology but in economics, politics, morality, ecology, art - everything. Not easy, of course, but he thinks it's possible."

Wednesday, August 8, 2012
Here is a short piece on the immortal dictator argument that shows up from time to time as one of the reasons given to continue to let billions die of aging: "But what if, the critics continue, you had a dictator who could live more or less for thousands of years? Wouldn't it be a good thing if he was guaranteed to die at some point and the people he oppressed had a chance to start anew? Wouldn't the sacrifice be worth it? No, it wouldn't, and here's why. Basically, we're being asked to give a potential means of extending our life spans so we can be sure that just a small handful of people and their cronies would be dead at some point in time. We can't always kill them or depose them, so we'll be outsourcing the assassination to nature. Anyone see the problem here? Of the over seven billion people who aren't dictators, who do we think is expendable enough to die alongside our targets for the sake of the anti-dictator cause? If I may reach for a little hyperbole, how different is the logic that all the billions who will die in the process are fair game because their death helps the cause from that of all terrorist groups who believe that civilians of the countries they hate can be on the hit list because killing them hurts an enemy and may force him to retreat? This is a rather crass way of saying that the ends justify the means and I doubt that they really do in this case. We could take this logic further and cast all modern medicine as being a dictator enabling technology. Maybe last week Assad would've tripped, fallen, hurt himself, then got his wound infected and was soon dead from septic shock, helping to end the civil war in Syria. Does this mean we must now give up our disinfectants and advanced medical treatments to make sure bad people die easier?"

Tuesday, August 7, 2012
Via ScienceDaily, news of a possible basis for a therapy to block the progression of dry macular degeneration: "Previous research [showed] that in human eyes with geographic atrophy [GA] there is a deficiency of the enzyme DICER1, leading to accumulation of toxic Alu RNA molecules in the retinal pigmented epithelium. Another paper [showed] that when these RNAs build up in the eye they trigger activation of an immune complex known as the NLRP3 inflammasome. In turn, this leads to the production of a molecule known as IL-18, which causes death of retinal pigmented epithelial cells and vision loss by activating a critical protein known as MyD88. Importantly, [researchers] found evidence that activity of the inflammasome, IL-18, and MyD88 were all increased in human eyes with GA. They then showed that blocking any of these components could prevent retinal degeneration in multiple disease models. The researchers are excited that blocking these pathways could herald a new potential therapy for GA, for which there is no approved treatment."

Tuesday, August 7, 2012
A conference to be held this coming December in Brussels: "Your presence can be key to convince the European Commission to count more on biology of ageing, preventive and regenerative medicine to extend healthy lives in the not so distant future. Heales (Healthy Life Extension Society) is a European non-governmental association promoting and advocating scientific research into longevity and biogerontology. We are a group of biologists, biochemists, medical doctors and diverse other professions throughout Europe. Having followed the evolution of the European Innovation Partnership on Active and Healthy Ageing we have reached the conclusion that biology of ageing needs to be highlighted more clearly as an important solution. Innovations based on biology of ageing can contribute to improve healthy life in a very significant way and we want to address this message to the European Union through this conference. In this conference, we will let scientists explain how their research contributes or can contribute to extend the healthy lifespan of European citizens; we will put scientists, entrepreneurs, medical doctors and other key actors together to build the business of long term health, towards a living Europe rather than a dying Europe. We hope that people who work for the European Union, politically active persons and others will be interested and will further help biology of aging reach concrete implementations."

Monday, August 6, 2012
Advice on financial planning for those who are not paying attention to progress in medicine: "My take on the mortality tables [used in financial planning]: they are excessively pessimistic. The mortality tables assume a fairly static biomedical treatment environment in which only small incremental improvements to medical care are possible. No discontinuities are part of the forecast. This seems a very big mistake. On the horizon we can see the approach of effective gene therapies, cell therapies, and other treatments that attack the underlying mechanisms of aging. The scientists doing research on these treatments will succeed. Once they do we will have biotechnology that enables us to repair aged tissue. For a long time mortality has declined fairly slowly. That's because we've had no tools for attacking the underlying mechanisms of aging. Our bodies gradually wear out just like bodies 50 or 100 years ago. We've got medical treatments that reduce the consequences of failing tissue (e.g. blood pressure medicine) and treatments that slow the rate of development of some types of problems (e.g. cholesterol lowering drugs). But we can't do much about the rate at which we accumulate mutations or the rate at which we accumulate toxic intracellular junk. We aren't going to stay helpless against aging tissues. The legions of scientists experimenting with pluripotent stem cells, tissue engineering, gene therapies, and other promising therapies will succeed and they will succeed in the first half of the 21st century. Once we can fix and replace failing parts the mortality tables go out the window as we gain the ability to do what we can now do to old cars: replace parts and keep on going. At some point in the 21st century we will reach actuarial escape velocity where the rate at which we can repair the body exceeds the rate at which pieces of the body wear out and fail. Our rejuvenated bodies will then go on for many more decades and eventually centuries. In a nutshell: If you are in your 30s or below I think your odds of dying of old age are remote. Whether folks in their 40s, 50s, and beyond will live to benefit from rejuvenation therapies probably depends on how long they will live naturally. Someone who is 50 years old and has 40 years to go even without biomedical advances will certainly live long enough to enjoy the benefits of biotechnologies that will enable them to live well beyond 90 years."

Monday, August 6, 2012
The BBC on intermittent fasting, from the Horizon series: "Scientists are uncovering evidence that short periods of fasting, if properly controlled, could achieve a number of health benefits. ... Calorie restriction, eating well but not much, is one of the few things that has been shown to extend life expectancy, at least in animals. We've known since the 1930s that mice put on a low-calorie, nutrient-rich diet live far longer. There is mounting evidence that the same is true in monkeys. ... One area of current research into diet is Alternate Day fasting (ADF), involving eating what you want one day, then a very restricted diet (fewer than 600 calories) the next, and most surprisingly, it does not seem to matter that much what you eat on non-fast days. [Researchers] carried out an eight-week trial comparing two groups of overweight patients on ADF. ... If you were sticking to your fast days, then in terms of cardiovascular disease risk, it didn't seem to matter if you were eating a high-fat or low-fat diet on your feed (non-fast) days."



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