Fight Aging! Newsletter, May 13th 2013

May 13th 2013

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

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  • Comments on Rapamycin and Metformin
  • Parabiosis Points to GDF-11 as a Means to Reverse Age-Related Cardiac Hypertrophy
  • Transgenic Mice Expressing Human MTH1 Live Longer
  • Forthcoming Book: the Ageless Generation
  • Boosted Mitophagy Extends Life in Flies By 25%
  • Discussion
  • Latest Headlines from Fight Aging!
    • The Present State of Artificial Retinas
    • The State of Electromechanical and Bioartifical Organs
    • Insights into Inflammaging
    • The Complement System and Rheumatoid Arthritis
    • More on Life Extension and Entitlements
    • UV Light, Nitric Oxide, and Blood Pressure
    • Aging, and the Cure of the Diseases of Aging
    • Towards a Patch for Damaged Hearts
    • Evidence Against an Influence of Mitochondrial DNA Haplotypes on Human Longevity
    • Reversing Hair Grayness By Suppressing Oxidative Stress


Three of the better known efforts to create a drug that modestly slows the rate of aging are centered on the following items:

  • Resveratrol analogs that target sirtuins
  • Rapamycin analogs that target mTOR
  • Metformin

Of these, ways to manipulate the activity of sirtuins have received the greatest attention over the past decade, but there is little to show for all that money and time beyond a modest gain in the understanding of metabolism. There are no replicated, solid results of life extension in mice via sirtuin-influencing drugs, and I'd go so far as to say that the field is under something of a cloud at present. Metformin is in a similar position: while a large body of work relates to its use as a treatment for type 2 diabetes, the evidence for its ability to extend life in laboratory animals is mixed at best. Rapamycin is the only one of the three that can boast solid, replicated evidence of life extension in mice. It is a drug that has been in use as an immunosuppressant for more than a decade, but its ability to extend life is a more recent finding.

For today I thought I'd point out a couple of open access items containing recent findings on the use of rapamycin and metformin in the context of aging. While I don't believe that this branch of research is particularly relevant to extending human life by any meaningful amount in the near term, it is interesting to watch and may help to shed more light on the relative importance of various aspects of our biology in aging. The metformin paper in particular is an educational attempt to tie in the senescent cell aspect of aging to study results:

Metformin, aging and cancer

Metformin, a widely used antidiabetic drug, has been linked to a reduced cancer incidence in some retrospective, hypothesis-generating studies. What is the mechanism by which aging may increase cancer incidence? Although many molecular changes correlate with aging, the presence of senescent cells capable of secreting inflammatory cytokines may be involved. This senescence associated secretory phenotype (SASP) consists of multiple cytokines, chemokines, growth factors and extracellular matrix degrading enzymes that can potentially affect normal tissue structure.

The SASP probably evolved as a gene expression program to assist the senescent tumor suppression response and tissue repair after damage and should be viewed as an initial adaptive response. However, [chronic] SASP [like chronic inflammation] may cause a microenvironment in old tissues that facilitates tumor initiation and then stimulates cancer cell growth.

This unfortunate interaction between senescent cells and cancer cells has been reproduced in experimental mouse models where senescent fibroblasts stimulated tumor progression. [During] experiments to study the potential cancer prevention activity of metformin, we found serendipitously that the drug prevented the expression of many proteases, cytokines and chemokines in senescent cells. We thus propose that metformin prevents cancer by modulating the SASP in tissues where senescent cells were not naturally cleared.

Prolonged Rapamycin treatment led to beneficial metabolic switch

In the first robust demonstration of pharmacologically-induced life extension in a mammal, rapamycin increased longevity of mice via either feeding or injection. However, rapamycin treatment also showed the detrimental metabolic effects, including hyperinsulinemia, hyperlipidemia, glucose intolerance and insulin resistance. Those observations present a paradox of improved survival despite metabolic impairments. How rapamycin extended lifespan with such paradoxical metabolic effects remains to be elucidated.

In the various studies of rapamycin treatment, length of rapamycin treatment varied from two weeks to two years. With short-term rapamycin treatment, mice showed the detrimental metabolic effects, while a much longer length (up to 1.5 to 2 years) of rapamycin treatment led to increased longevity. Duration of rapamycin treatment may be one of the key factors that determine outcomes of the treatment. Longer-term rapamycin treatment may cause beneficial metabolic "switch" that is associated with enhanced insulin signaling and extended longevity.

We [recently] reported that duration of rapamycin treatment indeed has differential effects on metabolism. In our study, rapamycin was given to mice for two, six or 20 weeks. Consistently with the previous reports, mice with two weeks of rapamycin treatment had characteristics of metabolic syndrome. Mice with six weeks of rapamycin treatment were in the metabolic transition status. When rapamycin treatment continued for 20 weeks, the detrimental metabolic effects were reversed or diminished.

It's worth taking some time to look over the state of research for these front-runners in the old-school drug discovery approach to extending life. I find it serves well as a way to inoculate yourself against unfounded optimism and unreasonable expectations, both now and the next time that both the "anti-aging" marketplace and biotech startups tout something that you can buy to supposedly influence metabolism and aging. If you have an enthusiasm for living longer, better to channel it into exercise, calorie restriction, and fundraising for the SENS Research Foundation.


Parabiosis involves joining the circulatory systems of two animals. This is of interest for a number of studies in which old mice and young mice are linked together, known as heterochronic parabiosis. The young mice acquire a little of the metabolic, cellular, and gene expression changes characteristic of old mice, while in the the old mice some of these measures reverse towards more youthful levels. In stem cell activity in particular, the environment of signals present in the blood seems to dictate age-related decline as much as does any inherent damage to stem cells or their niches. This reinforces the view of stem cell aging as an evolved reaction to the cellular damage of aging that acts to extend life by reducing cancer risk, but at the cost of a slow decline into death due to ever more poorly maintained tissues and organs.

Heterochronic parabiosis studies in mice have been taking place for some years now, and researchers are beginning to link differences in gene expression and protein levels in old tissues versus young tissues to specific age-related conditions. The next logical step is to see if age-related dysfunction can be reversed by changing these protein levels in old animals:

Young blood reverses heart decline in old mice

Pumping young blood around old bodies - at least in mice - can reverse cardiac hypertrophy - the thickening and swelling of the heart muscle that comes with age and is a major cause of heart failure. After just four weeks, the older mouse's heart had reverted to almost the same size as that of its younger counterpart. The hearts of the young mice were unaffected, even though they were pumping some blood from the older mice.

After ruling out the effect of reduced blood pressure on the older mice, the team identified a potential candidate: a protein called GDF11, which was present in much higher quantities in the blood of the young mice. To test the effect of GDF11, the researchers gave old mice with cardiac hypertrophy daily injections of it for 30 days. At the end of the treatment, their hearts were significantly smaller than those in a second group of mice of the same age and with the same condition, but that had been injected with saline.

Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy

The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation.

Using modified aptamer-based proteomics, we identified the TGF-β superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging.

Overriding declines in stem cell activity and forms of tissue degeneration by changing the levels of protein signals present in aged tissues is clearly going to be an important field of medicine in the near future. It may ultimately even take over from stem cell transplants as the principle mode of treatment for many age-related conditions. Some of those transplant therapies are most likely working through the same mechanisms, after all. Regeneration happens because the introduced stem cells are altering the signaling environment and waking up native stem cells, not because they are building new cells and patching up tissue structures.

However, one caveat is that this sort of work doesn't address any of the cellular and molecular damage that initiated the evolved response to reduce stem cell activity. That damage is still there: mitochondrial DNA mutations, high levels of oxidative damage, harmful build up of various forms of metabolic byproducts in and around cells, and so on. At the very least one would expect a growing risk of cancer to accompany a resurgence in stem call activity in an old person - which may be an entirely acceptable risk as cancer therapies improve past chemotherapy and towards targeted cell killers with no side effects.

Even if short term benefits can be obtained via altered signaling protein levels in old tissue, it is still the case that the underlying damage of aging must be repaired. Boosting stem cell activity so far appears to be a better class of potential treatment for many conditions than the best of what can be found in the clinic today, but it is still a form of patching over the underlying causes rather than fixing them.


New ways to extend mouse life span arrive at a steady pace these days. It's all largely genetic engineering to alter the operation of metabolism in various ways, and the results help to shed light on the roles of specific genes and on the way in which metabolism and environment together determine the pace of aging. These examples of life extension are not rejuvenation, however, and nor do they lie on any road that leads to rejuvenation. Thus they have little to no bearing on whether or not you and I will lead extended healthy lives: the only way that will happen is for research programs like SENS to make significant progress. SENS-like research aims to repair the underlying causes of aging in a deliberate, targeted fashion and thus reverse aging. It is a completely different approach to research and the development of therapies than that of trying genetic alternations in search of those that can modestly slow down aging.

But still, I post on the topic of genetically engineered mouse longevity for the same reasons I post on topics like the evolution of aging - because it is interesting, not because it will necessarily have any meaningful application in the near term. Below is a recent example in which the human gene for MTH1 / NUDT1 causes enhanced longevity when expressed in mice. The enzyme produced from this genetic blueprint cuts down on oxidative damage to both nuclear and mitochondrial DNA, and the gain in mouse life span is thus an expected outcome under any of the free radical theories of aging.

Prolonged Lifespan with Enhanced Exploratory Behavior in Mice Overexpressing the Oxidized Nucleoside Triphosphatase hMTH1

In this study we used the hMTH1-Tg mouse model to investigate how oxidative damage to nucleic acids affects aging. hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxodGTP and 8-oxoGTP and excludes 8-oxoguanine from both DNA and RNA. Compared to wild-type animals, hMTH1-overexpressing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in wild-type mice.

These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates. Neither lipid oxidation nor overall antioxidant status are significantly affected by hMTH1 overexpression. The significantly lower levels of oxidized DNA/RNA in transgenic animals are associated with behavioral changes. These mice show reduced anxiety and enhanced investigation of environmental and social cues.

There some muddying of the water here, of course. Nothing is ever simple in biology. The first item to consider is that it's possible that differences in activity levels in the mice could account for some of the longevity differences shown in the research. This is hard to control for, harder than calorie restriction, which is the other thing you have to keep track of in any mouse study. If your mice happen to eat less because your treatment makes them nauseous, or they eat less because they're spending more time running around, then they'll live somewhat longer.

The more interesting line item, however, is the difference between reducing oxidative damage to nuclear DNA versus reducing oxidative damage to mitochondrial DNA. There is some debate over whether nuclear DNA damage contributes meaningfully to aging (as opposed to its contribution to cancer risk), whereas there is a far greater consensus on the importance of mitochondrial DNA damage in degenerative aging. More of it is bad, less of it is good.

I would be very interested to see the results of a similar study in which researchers figure out how to keep the protective enzymes localized to either the nucleus or the mitochondria. My expectation would be that you'd only see increased life span for the mitochondrial localization, which would make sense when considering the extended life that result from studies in which levels of natural antioxidants like catalase are enhanced in mouse mitochondria.


Alex Zhavoronkov of the Biogerontology Research Foundation and the International Aging Research Portfolio (IARP) has written a popular science book that will be coming out next month. The topic is the defeat of aging, but the focus is on potential economic transformations, particularly those relating to unsustainable entitlements such as pensions, medicare, social security, and the like. These entitlements threaten the destruction of entire economies and societies by virtue of the fact that they cannot be continued indefinitely, and yet no group in society seems willing to do what needs to be done in order to avoid that result.

The Ageless Generation: How Advances in Biomedicine Will Transform the Global Economy

Historically, a continued failure to address national overspending has led to dire results: hyperinflation, extreme unemployment, civil unrest, and ironically, as economies collapse, a loss of funding for the same senior entitlement programs that created the crisis in the first place. Poor financial management was one of the main contributing factors behind the advent of Nazi Germany as well as the collapse of the USSR that put millions of its senior citizens into poverty. As Aldous Huxley warned, "That men do not learn very much from the lessons of history is the most important of all the lessons that history has to teach."

Will we learn from history? Fortunately, we may be bailed out by technology, which has advanced so rapidly in the past decade that a medical solution to these economic problems is now tantalizingly close. Through scientific means, we can dramatically enhance the health and youthfulness of the aging population over the next couple of decades.

This would redefine our current conception of 65 as the standard age of retirement. If tomorrow's 65-year-olds were as healthy as 55-year-olds today, seniors could work an extra ten years if they chose to do so. If millions of seniors continued to pay into the system while postponing their entrance into these senior entitlement programs by a decade or more, the problems of Social Security and Medicare could be pushed decades into the future. And the cycle would continue, as medical researchers would have more time to extend even further the health and vitality of seniors virtually eliminating the retirement age. As you will soon learn, the longevity breakthroughs we could see in the next 20 years could change the entire landscape of aging, including its social and economic implications.

Will we learn from history? The evidence to hand suggests that the answer is "no." The short term incentives for (a) those receiving entitlements and (b) the political elite who do well for themselves on the graft and corruption enabled by centralization of power combine to lead us all off the cliff in the end. The two sides even collaborate after a fashion in the system of voting for more entitlements. This, combined with an enormous military expenditure, is how all empires end - and the American empire-in-all-but-name will be no different.

I am skeptical that technological advances in medicine will do more than patch a small part of the overall problem. The problem is centralized, unaccountable power in the hands of those who make up the state. If it isn't social security that brings down the system in the end, at the point at which the elite run out of other people's money to steal, waste, and transfer to their allies, then it will be some other form of entitlement or abuse of the financial system.

The defeat of aging will of course be very welcome, and is a goal that should be pursued for what it can do to save lives and ameliorate suffering, not for its ability to let the corrupt upper crust continue being corrupt and in charge for a little longer. I am given to think that the technological advances that will do the most to help with the issues of power, entitlements, and economic destruction, are those involving space flight and cheap, reliable orbital access, however. Historically the only thing that has kept the depredations and corruptions of established states at least somewhat in check is the existence of an accessible frontier, a place to which large sections of the population can emigrate in order to escape a controlled, taxed, doomed economy. So very much of the malaise of the modern world is due, I think, to the lack of an effective frontier.


One of the side-effects of research into Parkinson's disease is that scientists are making more rapid progress in understanding the mechanisms of mitophagy than would otherwise be the case. Mitophagy is a set of quality control mechanisms that recycle mitochondria, the bacteria-like powerplants in our cells, and like the more general quality control mechanisms of autophagy it is important in aging and longevity. Boosted autophagy or mitophagy shows up in many of the genetic and metabolic alterations shown to extend life in laboratory animals, and has been shown to be required for some of them - no autophagy means no additional longevity.

This is all thought to be a matter of housekeeping: if cells and cellular components are more damaged or cluttered with waste products, then the life span of the organism is shorter as a result. If damage is reduced and more rapidly repaired when it does occur, life span lengthens. Mitochondrial damage in particular is thought to be connected to the pace of aging, by virtue of the fact that cells with damaged mitochondria can fall into malfunctioning states that export damaging reactive compounds to the surrounding tissues.

The focus on mitophagy in Parkinson's research has come about because some forms of Parkinson's are genetic in origin: the patients have a mutation in one of the proteins that form the machinery of mitophagy, making the process function less effectively. This translates to more damaged mitochondria, more cellular and mitochondrial dysfunction, and at the end of the day more dead dopamine-generating neurons. That last item, the loss of a specialized population of neurons, is the proximate cause of the symptoms of Parkinson's disease - but a range of low level biological process contribute to how exactly it happens.

I mention all of this because the research I wanted to point out today involves the protein called parkin: its association with Parkinson's disease was discovered prior to present theorizing on its involvement in mitophagy, hence the name. Researchers have now shown that more parkin means more mitophagy and longer-lived flies:

Single Gene May Extend Lifespan by 25 Percent

Scientists at UCLA have found a single gene that, when stimulated to be overexpressed, extends the healthy life span of fruit flies by more than 25 percent. The gene, called parkin, plays an important role in disposing of damaged proteins within a cell. Previous studies have suggested that protein build up within cells may play an important role in aging. In fruit flies, and potentially in humans, parkin "marks" damaged proteins and instructs the cell to dispose of them.

By stimulating parkin expression, thereby boosting the power of the "cellular garbage disposal," David Walker, lead author of the study, was able to keep a group of fruit flies alive much longer than normal. "In the control group, the flies are all dead by day 50. In the group with parkin overexpressed, almost half of the population is still alive after 50 days. We have manipulated only one of their roughly 15,000 genes, and yet the consequences for the organism are profound."

Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan

Aberrant protein aggregation and mitochondrial dysfunction have each been linked to aging and a number of age-onset neurodegenerative disorders, including Parkinson disease. Loss-of-function mutations in parkin, an E3 ubiquitin ligase that functions to promote the ubiquitin-proteasome system of protein degradation and also in mitochondrial quality control, have been implicated in heritable forms of Parkinson disease. The question of whether parkin can modulate aging or positively impact longevity, however, has not been addressed.

Here, we show that ubiquitous or neuron-specific up-regulation of Parkin, in adult Drosophila melanogaster, increases both mean and maximum lifespan without reducing reproductive output, physical activity, or food intake. Long-lived Parkin-overexpressing flies display an increase in K48-linked polyubiquitin and reduced levels of protein aggregation during aging. Recent evidence suggests that Parkin interacts with the mitochondrial fission/fusion machinery to mediate the turnover of dysfunctional mitochondria. However, the relationships between parkin gene activity, mitochondrial dynamics, and aging have not been explored.

We show that the mitochondrial fusion-promoting factor Drosophila Mitofusin, a Parkin substrate, increases in abundance during aging. Parkin overexpression results in reduced Drosophila Mitofusin levels in aging flies, with concomitant changes in mitochondrial morphology and an increase in mitochondrial activity. Together, these findings reveal roles for Parkin in modulating organismal aging and provide insight into the molecular mechanisms linking aging to neurodegeneration.

The theory at least is that the resulting life extension in flies is due to boosted mitophagy, and thus a greater pace of recycling of damaged mitochondria. The current understanding of the machinery involved is that parkin interacts with mitofusin to label mitochondria for destruction. Equally at this stage in the research, it might also turn out to be the case that a related but different process is adjusted by overexpressing parkin - there's still room for uncertainty, but time will tell one way or another.


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, May 10, 2013

Retinal implants that can provide a crude substitute for vision in some forms of blindness are a work in progress at this time, but the path ahead seems fairly clear:

Some people with artificial retinas can read large letters, see slow-moving cars, or identify tableware. Other patients experience no benefit. The variation can be ascribed in some cases to the exact placement of the neuron-stimulating array in the tissue-paper-thin retina as well as the state of the remaining neurons and pathways in each individual's eye. How well people can learn to use the device and retrain their brain is also important. At its best, the current level of vision is very pixelated. What's seen are bursts of light called phosphenes. "It's not restoring vision like you and I think of, it's restoring mobility. They provide contrast so that someone can see a difference in light and dark to the point where they can tell how to walk through a doorway. This is very much the beginning. Retina prostheses are at the stage cochlear implants were 30 years ago. That technology went from being an aid for lip reading to the point now where children with a cochlear implant can go through normal school and even use mobile phones. With retinal implants, we now know it has clinical benefit to patients, and I think we are going to see this technology develop very rapidly over the next decade."

Thousands of pixels [in comparison to the present 60 or so] will likely be required for facial recognition and other detailed visual tasks, and many artificial retina technologies will have trouble getting to such large numbers of pixels because they depend on wires. Wires are used to connect a power supply to electrodes, which requires a surgical procedure to lay the connection through the eyeball. To avoid this limitation, [researchers] are developing a wireless system that transmits image data captured by a video camera to a photovoltaic chip in the eye. Instead of transmitting visible light to the chip, his system uses near-infrared light that is beamed to flexible arrays of small pixels in the retina. The team has tested the system in blind rats and is now working with a company to test the device in patients. But even thousands of pixels are a long way from one million, "which is roughly what we have in the natural eye. And even at that, there is a lot of processing that the retina does that we are going to be skipping with an artificial retina."

Friday, May 10, 2013

An article on the development of prosthetic organs, a field that continues to provide competition for regenerative medicine:

Proponents of biological organ replacements have recently been encouraged by the development of 3D tissue printing, which offers the tantalising possibility that we might build organs mechanically, layer by layer - a much faster process than growing them in the lab. But printing complex internal organs like the liver or heart is still some way off, and the technology will face similar issues to traditional tissue engineering when it comes to implanting. In the meantime, some scientists are pursuing a different approach, combining biological tissue with synthetic materials and/or mechanical and electronic components to create what could be called hybrid or even cyborg organs (cyborgans, if you will), which are more easily manufactured, longer lasting and more successful once implanted into the body.

On one level this means incorporating some biological material into a largely man-made device. French firm Carmat [has] begun animal trials on one of the world's most advanced designs for an artificial heart, which includes some biological elements.The two chambers inside the Carmat heart are each divided by a biomembrane that separates blood on side from hydraulic fluid on the other. Tiny motors controlled by an electronic sensor system pump the hydraulic fluid in and out of the chambers, in turn causing the membrane to pump the blood. To increase haemocompatiblity, the membrane is made from animal tissue that helps move the blood without damaging cells. Microporous biological and synthetic biomaterials also cover every other surface that comes in contact with the blood, in order to prevent material from sticking to them.

But scientists are also combining biological and synthetic materials in a more fundamental way, creating permanent artificial structures or scaffolds and then growing living cells around them. [Researchers are] already preparing to clinically trial blood vessels and tracheae (windpipes) made in this way, and [are] also developing urethrae, bladders and cardiac patches for healing hearts.

Thursday, May 9, 2013

In later years the immune system falls into a malfunctioning state of overactivation and ineffectiveness, generating damaging chronic inflammation while at the same time failing to defend against pathogens and destroy damaged cells.

It is recognized that the immune system, comprising both innate (nonspecific) and acquired (specific) components, is an intricate defence system that is highly conserved across vertebrate species, and has, from an evolutionary perspective, undergone strong pressures to maximize survival to allow procreation. The significant improvements in human survival and lifespan to well beyond childbearing ages have been totally "unpredicted" by evolution. As a consequence, human immune systems are exposed to considerable additional antigenic exposure outside the forces of natural selection. It is in this situation that immunity begins to exert negative effects on human ageing (antagonistic pleiotropy), leading to gradual systemic failures.

Research into age-related changes of the immune system is gathering pace as its importance within the context of multiple pathologies in ageing populations is realized. As part of this advance, [researchers] described the phenomenon of "inflammaging" at the turn of the millennium as part of the spectrum of immunosenescence. Inflammaging denotes an upregulation of the inflammatory response that occurs with age, resulting in a low-grade chronic systemic proinflammatory state.

Inflammaging is believed to be a consequence of a cumulative lifetime exposure to antigenic load caused by both clinical and subclinical infections as well as exposure to noninfective antigens. The consequent inflammatory response, tissue damage and production of reactive oxygen species that cause oxidative damage also elicits the release of additional cytokines, principally from cells of the innate immune system but also from the acquired immune response. This results in a vicious cycle, driving immune system remodelling and favouring a chronic proinflammatory state where pathophysiological changes, tissue injury and healing proceed simultaneously. Irreversible cellular and molecular damage that is not clinically evident slowly accumulates over decades.

Thursday, May 9, 2013

Autoimmune diseases like rheumatoid arthritis are one of the few remaining classes of condition where little can be done for many sufferers at this time, and where researchers still know comparatively little about specific causative mechanisms. The most effective treatments are based on suppressing the immune system rather than addressing root causes, and even those are hit and miss.

Meanwhile here is one of the signs that this may all be changing in the years ahead, as modern tools allow a greater understanding and ability to manipulate facets of the immune system:

"We found that fat in the knee joints secretes a protein called pro-factor D which gives rise to another protein known as factor D that is linked to arthritis. Without factor D, mice cannot get rheumatoid arthritis." [With] the discovery of pro-factor D in mice with rheumatoid arthritis, [researchers are] working on gene therapies to eliminate the protein in localized areas. However, these findings still need to be extended to humans. "We are looking at vaccines, drugs or inhibitors to stop the local secretion of pro-factor D in the mouse. Our goal would be to stop the disease before it progresses and leads to joint destruction."

Factor D is part of the complement system, a complex array of over 40 proteins that help the body fight off bacteria and other pathogens. In studies with arthritic mice, [researchers] previously found that the complement pathway involving factor D made the mice susceptible to inflammatory arthritis. [Removing] factor D, rather than the entire complement system, achieves the same result without compromising other parts of the system that can fight infection.

While it's theoretically possible to destroy the entire complement system in humans to prevent arthritis, it eventually returns along with a renewed risk of contracting the disease. In the meantime, patients can get infections and other complications because they lack this critical part of the immune system. "The complement system is both friend and foe. We believe we can shut down one part of the complement system that triggers disease without shutting down the rest. If so, we will be making a major stride toward treating and perhaps even curing rheumatoid arthritis."

Wednesday, May 8, 2013

To go along with yesterday's post on the economic disaster of entitlements, here's another piece from someone who sees this as a defining issue in which longevity is important. Yet even if life spans were not increasing and even without the prospect of radical life extension in the near future, states would still be on a path to eventual collapse through growth in entitlements, forced transfers of wealth, and the accompanying corruption that arises with the centralization of power. This is the historical outcome resulting from the growth of a state in its late stages, even in periods of history without ongoing increases in life expectancy.

Truly historic discoveries and therapies are coming online right now that will radically decrease the threat and cost of autoimmune disorders, cancers, cardiovascular disease, Alzheimer's, arthritis, obesity and diabetes, as well as dangerous influenzas, HIV and other virus-borne diseases. [Clearly], this is good news both for humanity in general and investors specifically. However, these changes will be, by definition, enormously disruptive. As is always the case when big changes create new winners and dethrone the old ones. How big will these changes be?

Consider the fact that already, life extension is our No. 1 public-policy challenge. It is, in fact, the root cause of our current mortgage and debt fiascos - both only symptoms of successful life-extending technologies. The technologies that have precipitated these crises, however, will soon be overshadowed by the wave of revolutionary biotech innovation. Even those who have no personal interest in life-extension strategies, beyond those supplied by conventional medical networks, will have to deal with the social and economic problems they cause. Our lives will be profoundly affected by emerging biotechnologies that will push maximum healthy life spans up much faster and further than ever before.

Typically, when I say that life extension brings problems, the default assumption is that I'm referring to traditional fears of resource depletion and overpopulation. I'm not. [To] be clear, there is nothing about longer lives that is inherently adverse. Personally, I'm completely in favor of much longer health spans. Rather, the problem has been the failure to recognize and adjust to accelerating increases in life expectancies. This failure has led to ballooning expenditures and unsustainable debt. I should clarify and restate this thesis: Obsolete actuarial tables and expectations about the length and cost of retirement, especially on the medical cost front, are the proximate causes of the international fiscal meltdown.

Though many people portray the crisis as ideological, especially if their proposed solution is raising taxes, it's actually about math. And it's pretty simple math at that. The working young, who have always paid a disproportionate portion of the retirement and medical costs of the older and generally wealthier population, cannot bear that load in a demographically transforming world.

I would be one of those who see this as ideological. Present economic crises are caused by the ideologies that say its fine to force people to create a communal pool of funds under the control of elites, to suppress free markets in insurance and medicine, to force people to use fiat currencies that allow enormous levels of debt spending by elites, and so on and so forth. All these things trace back to the existence of a coercive state, its inexorable growth, and its inevitable corruption.

Wednesday, May 8, 2013

Nitric oxide levels show up in a range of mechanisms linked to aging and general health, in particular those to do with blood vessel function. Here is an interesting study that may or may not be examining an example of hormesis, a beneficial response to very minor levels of damage caused by UV light, such as that in sunlight:

Researchers have shown that when our skin is exposed to the sun's rays, a compound is released in our blood vessels that helps lower blood pressure. The findings suggest that exposure to sunlight improves health overall, because the benefits of reducing blood pressure far outweigh the risk of developing skin cancer.

Production of this pressure-reducing compound - called nitric oxide - is separate from the body's manufacture of vitamin D, which rises after exposure to sunshine. Until now it had been thought to solely explain the sun's benefit to human health. [Researchers] studied the blood pressure of 24 volunteers who sat beneath tanning lamps for two sessions of 20 minutes each. In one session, the volunteers were exposed to both the UV rays and the heat of the lamps. In the other, the UV rays were blocked so that only the heat of the lamps affected the skin. The results showed that blood pressure dropped significantly for one hour following exposure to UV rays, but not after the heat-only sessions. Scientists say that this shows that it is the sun's UV rays that lead to health benefits. The volunteers' vitamin D levels remained unaffected in both sessions.

"We suspect that the benefits to heart health of sunlight will outweigh the risk of skin cancer. The work we have done provides a mechanism that might account for this, and also explains why dietary vitamin D supplements alone will not be able to compensate for lack of sunlight. We now plan to look at the relative risks of heart disease and skin cancer in people who have received different amounts of sun exposure. If this confirms that sunlight reduces the death rate from all causes, we will need to reconsider our advice on sun exposure."

Tuesday, May 7, 2013

An essay on the causes of aging and what we might do to prevent them can be found at the SENS Research Foundation outreach blog:

The diseases of old age. Age-related disease. The diseases of aging. We've all heard this language used by medical experts. But what do we mean by them? What is the mysterious connection between aging and the diseases of aging? And how is SENS Research Foundation targeting that connection to keep people healthy and prevent and cure the suffering of old age's diseases and disabilities?

While we sometimes prefer not to think about it, we all know that people lose their health as they age. Angina, Alzheimer's, breast and prostate cancers, chronic kidney disease ... With rare exceptions caused by birth defects, severe congenital mutations, or traumatic injury, these diseases are never present in young adults. Their first subtle hints crop up in the years between our forties and our seventies, accompanied by the weakening of our muscles (even in athletes), loss of cushioning in our joints, failing of the eyesight, and a generalized decay of the body's resilience and health. Over time, the minor aches and vague malaise of middle age devolve more or less rapidly into clinical diagnoses, leaving us with a rising burden of disease, disability, and dependence.

But why does this happen? What is it about these diseases that causes them to slowly creep into our bodies after decades of relatively healthy life, each joining and building on the others, as if they were so many poorly-coordinated orchestra musicians, playing at different speeds, starting at different times, and raising a cacophony that gets louder and louder until it reveals itself as a terrible, secret symphony? And what can the answers to those questions tell us about what to do about them?

Tuesday, May 7, 2013

Progress is noted in the techniques needed to build functional heart tissue:

Biomedical engineers have grown three-dimensional human heart muscle that acts just like natural tissue. This advancement could be important in treating heart attack patients or in serving as a platform for testing new heart disease medicines. The "heart patch" grown in the laboratory from human cells overcomes two major obstacles facing cell-based therapies - the patch conducts electricity at about the same speed as natural heart cells and it "squeezes" appropriately. Earlier attempts to create functional heart patches have largely been unable to overcome those obstacles. The source cells used by [the] researchers were human embryonic stem cells. These cells are pluripotent, which means that when given the right chemical and physical signals, they can be coaxed by scientists to become any kind of cell - in this case heart muscle cells, known as cardiomyocytes.

"The structural and functional properties of these 3-D tissue patches surpass all previous reports for engineered human heart muscle. This is the closest man-made approximation of native human heart tissue to date. In past studies, human stem cell-derived cardiomyocytes were not able to both rapidly conduct electrical activity and strongly contract as well as normal cardiomyocytes. Through optimization of a three-dimensional environment for cell growth, we were able to 'push' cardiomyocytes to reach unprecedented levels of electrical and mechanical maturation."

"Currently, it would take us about five to six weeks starting from pluripotent stem cells to grow a highly functional heart patch. When someone has a heart attack, a portion of the heart muscle dies. Our goal would be to implant a patch of new and functional heart tissue at the site of the injury as rapidly after heart attack as possible. Using a patient's own cells to generate pluripotent stem cells would add further advantage in that there would likely be no immune system reaction, since the cells in the patch would be recognized by the body as self."

Monday, May 6, 2013

A range of studies suggest that variations in mitochondrial DNA influence human longevity, which is what we'd expect given the mass of evidence for the importance of mitochondria DNA damage in aging, and the role of mitochondrial function in many age-related diseases. Here, however, is a study showing no statistically identifiable effects resulting from different mitochondrial DNA haplotypes in the old:

Inherited genetic variation of mitochondrial DNA (mtDNA) could account for the missing heritability of human longevity and healthy aging. Here, we show no robust association between common genetic variants of mtDNA and frailty (an "unhealthy aging" phenotype) or mortality in 700, more than 85-year-old, participants of the Newcastle 85+ study. Conflicting data from different populations underscore our conclusion that there is currently no compelling link between inherited mtDNA variants and aging.

Monday, May 6, 2013

The graying of hair with increasing age is an early sign of increased oxidative stress in skin tissues around hair follicles. Researchers here demonstrate that it can be locally reversed by an antioxidant-based strategy. This shouldn't be taken to indicate that antioxidants are of general utility: the researchers are carefully augmenting the role of a specific natural antioxidant enzyme in an intricate chemical process, not just picking any random antioxidant and throwing it into the mix.

People who are going gray develop massive oxidative stress via accumulation of hydrogen peroxide in the hair follicle, which causes our hair to bleach itself from the inside out. The build up of hydrogen peroxide was caused by a reduction of an enzyme that breaks up hydrogen peroxide into water and oxygen (catalase). Hair follicles could not repair the damage caused by the hydrogen peroxide because of low levels of enzymes that normally serve this function (MSR A and B). Further complicating matters, the high levels of hydrogen peroxide and low levels of MSR A and B, disrupt the formation of an enzyme (tyrosinase) that leads to the production of melanin in hair follicles. Melanin is the pigment responsible for hair color, skin color, and eye color.

The report shows that this massive accumulation of hydrogen peroxide can be remedied with a proprietary treatment developed by the researchers described as a topical, UVB-activated compound called PC-KUS (a modified pseudocatalase). What's more, the study also shows that the same treatment works for the skin condition, vitiligo.


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