Fight Aging! Newsletter, March 25th 2013

March 25th 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!



- The Fable of the Dragon-Tyrant, Animated
- We Already Live in a Gerontocracy
- In Search of a Useful Scientific Definition of Aging
- Evidence Against the Role of Nuclear DNA Damage in Aging
- Discussion
- Latest Headlines from Fight Aging!
    - A Look at the Aging Liver
    - Comments on Recent Research Relevant to Combating Aging
    - Considering Longevity, Aging, and Medical Science
    - An Update on Trialing Engineered T Cells Against Leukemia
    - Further Investigation of Deer Antlers
    - A Possibly Important Finding in Alzheimer's Research
    - Publicity for the 2045 Initiative
    - An Interview With David Ettinger
    - A Look at Halting or Reversing Thymic Involution
    - A Review on the Topic of Microglia in Aging


Nick Bostrom's Fable of the Dragon-Tyrant is a noted modern morality tale, written to highlight our acceptance of death by aging, and more importantly our grand, widespread failure to work towards building therapies to treat aging. Even though the research community now knows enough to achieve that goal, and even though biotechnology is in the midst of an unprecedented revolution in capacity and capabilities, research aimed at producing human rejuvenation is hardly funded at all in comparison to other more prosaic fields.

Further, if asked, most people gladly declare that they have no interest in living longer or treating aging as a disease to be cured - despite the fact that they would no doubt be among the masses taking advantage of rejuvenation therapies were those treatments available, just as they now take advantage of modern medicine unavailable to their ancestors. So we march towards death and suffering, doing next to nothing about this avoidable fate. It is this sort of everyday madness that inspires the writing of fables.

You might recall that a couple of years back there was some talk of animating the Fable of the Dragon-Tyrant. This was generally agreed to be a good idea. I'm pleased to note that someone actually went ahead and did it. Follow the link above to watch the animation.


Gerontocracy: government by a council of elders, or government by old people. There are many knee-jerk reactions to the prospect of greatly increased healthy human life spans, most based on mistaken beliefs regarding the technologies needed, or mistaken beliefs regarding the way the world actually works - economics, human action, incentives. Some people believe that longer lives will result in stagnation, which is actually one of the more ridiculous and improbably outcomes once you start to pick it apart in any detail. Human society is restless and changeable on timescales far shorter than current lifespans, and the reasons why are rooted in day to day human nature. Our ambitions operate on a horizon of a few years, and that wouldn't change all that much were we to live for centuries. We are driven to influence the world today, now, regardless of the years that lie ahead of us. So the fashions of this year are gone by the next. The idols of popular culture rise and fall with rapidity. The political and business leaders of this decade are gone in the next, displaced by peers. Even corruption and revolution on a grand scale are usually only a matter of a few decades, not lifetimes.

Nonetheless, rationality rarely prevails in knee-jerk reactions - so folk think of stagnation, even in the midst of this boundlessly energetic society we live in, packed wall to wall with constant, ongoing change. A subset of these beliefs on human longevity and stagnation involve the nebulous fear of a future gerontocracy, the rise of a self-perpetuating ruling elite of ageless individuals. Funnily, this is often voiced by people who are, unlike myself, perfectly comfortable with today's Western governments. I say funnily because I have to ask: are not our present societies already gerontocracies? Isn't any civilized society a gerontocracy? Who has had the most time to gather connections, a network, and make good use of them? The old. Who has had the most time to gather resources and invest them? The old. Who has had to most time to become truly talented and sought after? The old. Who has had the most time to work their way through a social hierarchy to challenge its existing leaders? The old. Where then will the elite and the leaders tend to arise? From the old.

Take a look at who just runs and influences companies, governments, knitting circles, successful non-profit initiatives, extended families, and so on and so forth for every human endeavor. Young leaders exist, but they are a minority among the ranks of the old. This is the natural state of affairs for any society that possesses enough technology to make thought and craft more important than strength and vigor.

All that is terrible in our present societies lies in the growing centralization of power, not the chronological age of those eagerly engaged in furthering the road to serfdom and empire. Even as power is centralized, there is still a year by year turnover of figures - even in the most defensible and corruptly secure positions of power and influence. They are largely kicked out by some combination of their peers and the mob in the sort of political anarchy that exists at the top, above the laws made for the little people. It is the rare individual who can stick it out long enough to be removed by the infirmities of age, even now, in this age of human lives that are all too brief in comparison to what is to come.

But back to the point. We live in a gerontocracy, and so did most of our ancestors. Yet change still happens just as rapidly as in past centuries when fewer people lived into later life in the sort of good shape they can manage today. Fear of some sort of comic-book gerontocracy emerging in the future seems, frankly, somewhat silly. The historical record shows that people at the top are not all that good at staying at the top for extended periods of time. There are always outliers, but they are rare in comparison to the vast majority of leaders and the famous who are just part of the churn, coming and going, displaced and quickly forgotten once their few years are done. The top of a pyramid is a challenging place to stand.


Commentary from Aubrey de Grey on the many definitions of aging and their consequences: "Surely everyone who studies the biology of aging fundamentally agrees on what it is they are studying, even if they may prefer somewhat different terminology to define it? I'm afraid you'd be wrong. Disagreement within the field about what aging really is and is not is very far from purely semantic, and the substance of those disagreements leads to profound differences of opinions concerning both what research gerontologists should prioritise and how they should communicate their work to others.

"First: is aging a disease? Some gerontologists will just tell you "No, it is separate from age-related diseases". Some will say "No, but it is a risk factor for age-related diseases". Some will say "No, it is the set of precursors of the age-related diseases". Some will say "Yes, it is the set of precursors of the age-related diseases"! Self-evidently, whether X is a Y depends not only on the definition of X but also on the definition of Y, so one might excuse this chaos on the basis of a failure to agree on what is and is not a disease - and there is indeed no such agreement. But it gets worse.

"Is aging a thing that is amenable, in principle, to medical intervention? Not if you believe the protestations of such eminent gerontologists as Bruce Carnes and Jay Olshansky, who in a recent paper critiquing (I employ classic British understatement in my choice of words here) various colleagues' work made, in spite of reviewers' efforts to educate them, the assertion that "What Wilmoth fails to acknowledge is that in order to reduce death rates at advanced ages to zero or close to it, our biology would need to be modified" (my emphasis). This sort of language, without stating explicitly that medicine can never maintain the body in a state of health so youthful that death rates will be vastly lower than today, unequivocally seeks to convey that view. So, do other gerontologists agree? Indeed they do not: if any evidence were needed, I may merely cite the fact that almost every mainstream conference on the biology of aging these days has a subtitle referring to delaying or even reversing aging.

"Finally, is aging even a bad thing? At least here we find broad consensus among biogerontologists - those who study the biology of aging (though there are a few exceptions). But the same does not apply to all gerontologists: those whose field is more on the clinical, or the sociological, side tend to be among the most viciously and vocally opposed to any talk (let alone action) concerning actually doing anything about aging. As an example, a very senior (and, I am afraid to say, highly influential) clinical gerontologist from Canada recently wrote to me as follows: "I do not wish in any way shape or form to have my name associated with anti-aging medicine, regenerative or restorative medicine or some such". No kidding. I will be interested to discover, at some point, whether she is willing to defend that view publicly.

"It should by now be apparent that there is a bit of a problem. Let me emphasise, however, just how much of a problem. At present, translational biogerontology (alternatively, biomedical gerontology) commands an absolutely minuscule proportion of the medical research budget of any industrialised nation. Why? Simply because the idea that postponing aging is a feasible and valuable goal, both socially and economically, has failed - despite the best efforts of many biogerontologists over many decades - to gain any significant traction among funding bodies. I contend that gerontologists' muddled thinking outlined above concerning what aging really is is actually the number one reason for this failure."


n some circles within the aging research community it is taken as read that accumulating damage to nuclear DNA - the DNA that resides in the nucleus of your cells - contributes to degenerative aging, most likely by causing cellular maintenance and other programs to run awry to an ever increasing degree. The nucleus of the cell is well protected, and equipped with extremely efficient DNA repair mechanisms, but nonetheless damage accumulates across the years. Being alive necessarily involves the generation of reactive chemical compounds, and sooner or later some of them run into the structure of DNA within a cell and react with it. The processes of DNA repair, while ever watchful, slip up once in a while and fail to fix the resulting breakage. Every cell bears its load of unrepaired mutations.

This sort of ongoing stochastic damage is certainly a contributing cause of cancer: the more mutations you suffer, the greater the chance that one or more of them manage to alter cellular programming in just the right way to create a cancerous cell, readily to act as the seed of a malignant neoplasm. That's just a numbers game - you can be unlucky and suffer cancer young, but you are far more likely to suffer cancer later in life.

But is nuclear DNA damage a cause of general degenerative aging? Is it actually a contributing cause of frailty, failing tissue maintenance, failing organs, and so forth? The point can be argued; Aubrey de Grey puts forward the position that the levels of nuclear DNA damage experienced don't rise to producing any significant effect outside of cancer risk over a human lifetime. If we live far longer than our ancestors, as we hope we might, this damage will probably become something that has to be dealt with at some point - perhaps via swarms of adaptive medical nanorobots akin to the chromallocytes envisaged by Robert Freitas.

Recent research adds weight to the suggestion that nuclear DNA damage is not a cause of aging: "Here, we quantified DNA damage in liver and brain of both normal and prematurely aging, DNA repair defective mice. The results indicate a marginal, but statistically significant, increase of spontaneous DNA damage with age in normal mouse liver but not in brain. Increased levels of DNA damage were not observed in the DNA repair defective mice. We also show that oxidative lesions do not increase with age. These results indicate that neither normal nor premature aging is accompanied by a dramatic increase in DNA damage. This suggests that factors other than DNA damage per se, e.g., cellular responses to DNA damage, are responsible for the aging phenotype in mice."


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, March 22, 2013
This paper examines some aspects of aging in the liver, giving a general review in the course of getting to a discussion on immune system changes that occur in aging and their influence on the liver. Note the importance of a buildup of unwanted protein byproducts inside liver cells, something that occurs due to the progressive failure of cellular housekeeping components known as lysosomes. You might recall that researchers reversed aspects of liver aging in mice a few years back by boosting lysosomal activity, so as to counteract some of the usual decline. "Although the human liver is not unscathed by the process of aging, the changes it undergoes are minor compared with other organ systems. It has been ascertained that there are no liver diseases specific to advanced age. However, the clinical course and management of liver diseases in the elderly may differ in several aspects from those of younger adults. Human and experimental studies suggest that, in comparison with other organs, the liver ages fairly well. Aging is however associated with a variety of morphological changes in the liver, but their underlying mechanisms are still unclear. The liver progressively shrinks by 20-40% during the course of a human life, and there is a concomitant age-related decrease in liver volume. The classic gross appearance of the liver in the elderly is known as "brown atrophy", and the brown is due to an accumulation of highly oxidized insoluble proteins, known as lipofuscin, stored into hepatocytes. These accumulations of highly cross-linked protein are thought to relate to chronic oxidative stress and a failure to degrade damaged and denatured proteins. Increasing evidence suggests that lipofuscin interferes with complex cellular pathways. One of the most important age-related changes in liver function observed in animal models is a significant decrease in regenerative capacity of the liver, but not in the capacity to restore the organ to its original volume. [It] has also been shown that aging is associated with multiple changes in. Elderly humans secrete less bile acid, have increased biliary cholesterol levels, and show an increased oxidative stress that is mainly attributable to a reduced capacity to eliminate metabolically generated superoxide radicals as efficiently as before. The reduction in hepatic blood flow during aging reduces the metabolism of rapidly cleared drugs. Aging of the liver is also associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins."

Friday, March 22, 2013
Commentary on various recently published research relevant to the SENS view of biotechnology to repair and reverse aging appears as an occasional feature at the journal Rejuvenation Research. The latest is open access, so take a look at the PDF format paper, containing commentaries such as this one on a method of wrapping enzymes in polymer nanocapsules to ensure their delivery to specific locations within cells or the body: "The accumulation of recalcitrant waste substances in cells' lysosomes is implicated in a wide spectrum of aging-related diseases, including atherosclerosis, age-related macular degeneration (AMD), and many others. Being one of the clearest examples of the build-up of "junk" in aging bodies, it is expected that means to degrade lysosomal waste will be among the first rejuvenation biotechnologies to reach clinical application. Indeed, the required development time before an effective therapy can be deployed is expected to be so brief that SENS Research Foundation devotes a substantial portion of its budget to identifying and refining enzymes for just this purpose. However, this tight schedule poses a specific problem; it is quite probable that hydrolases effective, for example, against 7-ketocholesterol (the dominant "junk" molecule in atherosclerotic plaque) or A2E18 (predominant in AMD) will be ready for clinical use before safe and effective somatic gene therapy becomes available. It will therefore be necessary to introduce these garbage-clearing enzymes into patients directly, rather than by genetically engineering the recipient's cells to produce them - an approach termed enzyme replacement therapy, currently in widespread clinical use to treat congenital lysosomal disorders. Of course, enzymes introduced into the body by such methods cannot be replaced once degraded (a particularly rapid fate in the harsh conditions of the lysosome), necessitating regular infusions to maintain their function. The polymer-coating method described in this study enhances the hardiness of the enzymes thus treated, and might be reasonably expected to thus appreciably reduce the required frequency of reintroduction, and/or minimise the dosages required (and hence any side-effects)."

Thursday, March 21, 2013
An open access review on the topic of aging and longevity, largely focused on mainstream work aimed at producing ways to gently slow aging by metabolic manipulation: "Aging drives disease. Nearly every major killer in developed countries shares a common feature: your risk of getting the disease increases dramatically as you get older. For example, the likelihood of being diagnosed with Alzheimer's disease doubles every five years after the age of 65. A similar kind of relationship can be seen for most types of cancer, heart disease, diabetes, kidney disease, and many others. What is it about getting older that simultaneously increases risk for all of these disorders? Are there common molecular changes that cause an organism to switch from youthful and healthy to aged and infirm? Can we intervene in this process to do something about it? These are some of the big questions that scientists who study the biology of aging are interested in answering. The perspective that most age-related disorders share a common underlying biology is a departure from traditional biomedical science, one that potentially offers a more powerful approach towards improving human health. Rather than focus on curing the individual disease, interventions that target the molecular processes of aging can simultaneously delay the onset and progression of most age-related disorders. Such an intervention is predicted to have a much larger effect on life expectancy than can be attained by treating individual diseases. This is because even if one disease is cured, the relationship between age and all the other disorders of aging still holds. For example, it has been estimated that curing cancer will lead to only a 3-5 year increase in survival for an average 50 year-old woman, while slowing aging to an extent that is routine in laboratory organisms has about a 5-10-fold greater impact on life expectancy. Importantly, these added years from slowing aging are spent largely free from chronic disease and disability, while the relatively small gains in survival by curing cancer (or any other individual disease of aging) are still associated with the inevitable age-related declines in function of every other bodily system. This concept of extending the period of life spent free from chronic disability and disease, referred to as healthspan, is a critically important idea in the field of aging-related research."

Thursday, March 21, 2013
Following on from research noted last year: "Genetically engineered immune cells can drive an aggressive type of leukaemia into retreat, a small clinical trial suggests. The results of the trial - done in five patients with acute lymphoblastic leukaemia - [represent] the latest success for a 'fringe' therapy in which a type of immune cell called T cells are extracted from a patient, genetically modified, and then reinfused back. In this case, the T cells were engineered to express a receptor for a protein on other immune cells, known as B cells, found in both healthy and cancerous tissue. "All of our patients very rapidly cleared the tumour. The treatment worked much faster than we thought." The next step [is] to move the technique out of the 'boutique' academic cancer centres that developed it and into multicentre clinical trials. "What needs to be done is to convince oncologists and cancer biologists that this new kind of immunotherapy can work." [A researcher] remembers the day that he had to tell one of the patients in the trial that the weeks of high-dose chemotherapy the 58-year-old man had endured had not worked after all. "It was painful to have that conversation. He tells me now it was the worst news he has ever heard in his life." Another month in the hospital on intensive chemotherapy drugs did nothing to help. By the time the man started the trial, 70% of his bone marrow was tumour. [Researchers] then extracted T cells from the patient and engineered them to express a 'chimeric antigen receptor', or CAR, that would target cells expressing a protein called CD19. Because CD19 is found on both healthy and cancerous B cells, the engineered T cells were unable to discriminate between the two. However, patients can live without B cells. By two weeks after the procedure, the patient was showing signs of improvement. The treatment had driven his cancer into remission - as it did for the other four patients in the trial - so he became eligible for a bone-marrow transplant. A hundred days later, he is doing well. Four of the five patients were well enough to receive transplants; the remaining patient relapsed and was ineligible."

Wednesday, March 20, 2013
One lesser branch of regenerative medicine is involved in searching the animal kingdom for examples of potent regeneration and seeking to understand the mechanisms involved. For example, there is the quest to discover whether the potential for salamander-like organ and limb regeneration, observed in many lower species, lies dormant in mammals by virtue of being an ancient process, evolved long ago and shared across most species. The jury is still out on that question - more work is needed. Searching for exceptional regeneration in mammals is also a viable strategy - there are fewer instances, but the thinking is that whatever mechanisms are involved would be easier to introduce to humans. Deer antlers are one of the better known examples, and here researchers dig into some the cellular biochemistry involved. This is a small start; there are actually very few researchers looking at deer in this way, probably fewer than are, say, working with regeneration in salamanders or zebrafish: "A team of researchers [have] reported finding evidence that deer antlers - unique in that they regenerate annually - contain multipotent stem cells that could be useful for tissue regeneration in veterinary medicine. "We successfully isolated and characterized antler tissue-derived multipotent stem cells and confirmed that the isolated cells are self-renewing and can differentiate into multiple lineages. Using optimized culture conditions, deer antler displayed vigorous cell proliferation." Deer antler is of interest, said the researchers, "because antlers are very peculiar organs in that they are lost and re-grown annually....a rare example of a completely regenerating organ in mammals." According to the researchers, they subjected deer antler to differentiation assays for osteogenic (bone), adipogenic (fat) and chondrogenic (cartilage) lineages under culture conditions specific for each lineage to confirm the multi-lineage differentiation ability of antler multipotent stem cells. They concluded that deer antler tissue might be a "valuable source of stem cells" that could "be a potentially useful source of regenerative therapeutics in veterinary science." The researchers noted that the development of deer-specific antibodies "is essential to confirm the identification of antler multipotent stem cells". They specifically noted that injury to wild animals, including deer, might be treated using deer antler derived cells. They also pointed out that studies involving the use of horse stem cells have found clinical application of equine-derived stem cells."

Wednesday, March 20, 2013
This has the look of something that might lead to an intermediary therapy for Alzheimer's disease, one that allows patients to better function despite beta amyloid build up - but it will be compensatory only, and won't solve the underlying damage and dysfunction of aging that causes beta amyloid to accumulate in the first place. "The scientific community so far has widely accepted that Alzheimer's disease is caused by the accumulation of a peptide called Amyloid beta. When Amyloid beta is applied to neurons, neuronal morphology becomes abnormal and synaptic function is impaired. However, how Amyloid beta causes dysfunction is unknown. [New] research indicates that the presence of Amyloid beta triggers increased levels of a signaling protein, called centaurin alpha 1 (CentA1), that appears to cause neuronal dysfunction - a potentially groundbreaking discovery that uncovers an important intermediary step in the progression of the disease. As part of the research, the scientists were able to identify CentA1 and measure its negative effects on neurons. Utilizing an RNA silencing technique, they turned down the cellular production of CentA1, and showed that affected neurons, exposed to Amyloid beta and exhibiting Alzheimer's related symptoms, returned to normal morphology and synaptic function, even with the continued presence of Amyloid beta. They further found that increased CentA1 activates a series of proteins, and these proteins form a signaling pathway from CentA1 to neuronal dysfunction. Thus, inhibiting other proteins in the pathway also "cured" affected neurons. The initial tests reported were conducted on rat brain slices. [Researchers have] already started to expand their studies to mouse models of Alzheimer's disease and preliminary experiments show promising results."

Tuesday, March 19, 2013
Some press for the 2045 Initiative: " Russian multi-millionaire is targeting the business community to raise money to fund a project that aims to make immortality a reality by 2045. It may sound like something straight out of a science fiction novel, but Dmitry Itskov, a 35-year-old media mogul, is seeking investors to fund research for technology that will make eternal life possible by transferring human consciousness in an artificial form to avatars (robotic bodies). Itskov is the founder of Initiative 2045, a non-profit organization focused on creating an international research center where scientists will research and develop the technologies to make eternal life possible. Last year, Itskov wrote a public letter to individuals on Forbes billionaires list asking them to invest in his project. While Itskov did not receive any public responses, he did accomplish his goal of getting word out about the project and he is continually in talks with wealthy individuals about his project, he said. "The goal was to get the public's attention," Itskov said. "I do communicate with some of the richest people in the world, but I can't share who they are." This summer, Itskov will make a pitch to not only to the world's most wealthy individuals, but the entire business community, to invest in his project as well as research and development in areas that help further his cause. In June, Itskov's organization will be hosting the second annual Global Future 2045 World Congress, an event where leading scientists, technologists and entrepreneurs will gather to discuss and demonstrate new technologies that are paving the way for life expansion."

Tuesday, March 19, 2013
An interview on the topic of cryonics, the low-temperature preservation of the body and brain following death. This aims to preserve the brain's fine structure - where the data of the mind is stored - so as to enable a chance at the development of future technologies to restore that individual to life: "Cryonics is based on a bet about the future, that technology will advance. A bet that we think is very sound, but is it evidence-based, it's not. Some people say, well do you have faith in cryonics? No, I just look at history and think this is a good bet. It's not certain by any means, but it's the best alternative. And that's how [Robert Ettinger] approached things. I mean, he wrote some articles about probability theory and what he called the probability of rescue. So cryonics was always from the first, scientifically based, and though there were people at the time who said this isn't going to happen, my father always challenged them and said, what's your evidence? Is the damage [caused by freezing] so limited that you can freeze and revive a person today? It is not. I mean, there is too much damage that we cannot reverse currently for that, but that's part of why you need more time, but people frozen have the time. [Robert Ettinger] said that what some people want, will not be satisfied. Some people will not be satisfied until someone is frozen, and revived, and lives forever. Well, we can't wait for them. The quicker you do it, the less damage will occur. And the process begins with cooling of the body, and especially the head, sometimes while continuing to pump the blood so that oxygenated blood flows to the brain and that limits the damage in the meantime. The next step is, and the cooling goes through several steps, starting with ice, then the body is perfused with cryoprotective agents to protect against damage in the freezing. You know, the next stage is dry ice and then liquid nitrogen vapors and ultimately liquid nitrogen, and the entire process takes a couple of days, takes a few days, really, to be finished."

Monday, March 18, 2013
Left to its own devices, your immune system supports a fairly fixed upper limit of T-cells, and the fraction of those cells that can respond effectively to new threats, or patrol the body to destroy senescent or precancerous cells, declines with age. On the one side ever more T-cells become specialized in futile attempts to deal with persistent but otherwise not terribly threatening viruses such as CMV, and thus become useless for other activities. On the other side, the new supply of T-cells dwindles to nothing as the thymus atrophies - a process called thymic involution, something that happens comparatively early in life. So a range of possible approaches could be taken to restore a sufficient number of aggressive T-cells to the body. Using stem cell technologies to create large numbers of a patient's own T-cells and then infuse them periodically, for example - that's possible today, but only being tried in trials for specific named diseases, as is usually the case for things that might be beneficial to all old people. Hopefully overseas clinics and medical tourism will pick up the slack. Other approaches involve destroying the unneeded specialized cells to free up immune system capacity, or trying to increase the supply of new immune cells by at least partially regenerating and restoring the thymus. "The thymus is a thumb-sized organ just above the sternum where our immune cells are trained to recognize self from other. It is fully developed by the time we are 10 years old, but after that it begins gradually to shrink. By age 25, it has already lost 30% of its mass, and by age 60 it is less than half its peak size. There is evidence that this is related to the immune decline that contributes so much to growing mortality risk with age, and that reversing that decline might lead to longer, healthier lives. Research on reversal of thymic [degeneration] is a backwater of medical science. If this is an opportunity for major gains in life expectancy, then it is a neglected opportunity that has attracted little interest or funding. Based on evolutionary arguments, the general attitude seems to be that if the thymus shrinks over a lifetime, then it must not be much needed; or, conversely, that a Law of Nature assures us that any therapy to maintain its function must necessarily have dangerous side-effects that outweigh the benefits. [But] this is ideology, a misplaced faith in general theory over explicit experimental results. Reality in the lab appears to be that: "Thymic involution [seems] to provide no obvious benefits in humans that would outweigh the benefits of [its] elimination once the hazards associated with such issues as insulin-like signaling can be set aside.""

Monday, March 18, 2013
Microglia are immune cells of the central nervous system (CNS). As is the case for the rest of the immune system, they are involved in the rising levels of chronic inflammation that accompany aging, inflammation that contributes to the development of neurodegenerative disease. Here is an open access review on this topic and the prospects for intervention: "Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and age-related macular degeneration (AMD), share two characteristics in common: (1) a disease prevalence that increases markedly with advancing age, and (2) neuroinflammatory changes in which microglia, the primary resident immune cell of the CNS, feature prominently. These characteristics have led to the hypothesis that pathogenic mechanisms underlying age-related neurodegenerative disease involve aging changes in microglia. If correct, targeting features of microglial senescence may constitute a feasible therapeutic strategy. This review explores this hypothesis and its implications by considering the current knowledge on how microglia undergo change during aging and how the emergence of these aging phenotypes relate to significant alterations in microglial function. Evidence and theories on cellular mechanisms implicated in driving senescence in microglia are reviewed, as are "rejuvenative" measures and strategies that aim to reverse or ameliorate the aging microglial phenotype. Understanding and controlling microglial aging may represent an opportunity for elucidating disease mechanisms and for formulating novel therapies."



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