Fight Aging! Newsletter, October 8th 2012

FIGHT AGING! NEWSLETTER
October 8th 2012

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

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CONTENT

- A Way to Target Senescent Cells
- A Speculative Order of Arrival for Rejuvenation Biotechnologies
- Video: Basil Gelpke Talks With Aubrey de Grey
- On Zinc Transport Dysregulation With Aging
- Discussion
- Latest Headlines from Fight Aging!
    - Noting Progress in Artificial Cornea Development
    - A Cryonics Photo Essay at Wired
    - Shared Mechanisms for Longevity via Calorie Restriction and AC5 Knockout
    - Reporting on a Recent Presentation by Aubrey de Grey
    - Telomere Length Alone is Not a Good Biomarker of Aging
    - Manipulating Immune Response to Boost Nerve Regeneration
    - Notes on Alcor's 2012 Strategy Meeting
    - Several Vital Cell Populations Could Grow in Lymph Nodes
    - What Failure Will Look Like: A Pill for Healthy Aging
    - Inroads into Making Old Immune Cells More Responsive

A WAY TO TARGET SENESCENT CELLS

Exciting signs of progress are emerging from research groups aiming to selectively destroy senescent cells, thus removing their contribution to degenerative aging:

https://www.fightaging.org/archives/2012/10/a-way-to-target-senescent-cells.php

"Last year, researchers demonstrated that the onset of age-related degeneration in mice can be delayed by culling senescent cells. The method used was convoluted, however, and involved gene therapy - which makes it a poor candidate for anything other than demonstrating that removal of senescent cells is a good thing. There's no building a near-term therapy from that work.

"The path to building a useful and straightforward therapy that kills senescent cells is pretty clear, however. There are any number of ways to kill a cell; the trick lies in picking out the cells you want to kill from the forest of their peers. Fortunately, the cancer research community has been very focused on this problem for many years now: how to deliver any of the proven cell-killing drugs to a specific set of cells that look slightly different from their neighbors without harming any of those neighbors. The past decade has seen great strides in the development of nanoparticles that can carry a payload, attached to some form of biological machinery capable of discriminating between cells based on one or more aspects of their surface chemistry. Flood the body with suitable nanoparticle delivery systems and they will find and kill only the cells you want to kill.

"Cell surface chemistry is complex and far from black and white, of course. Nonetheless, work on targeting and delivery mechanisms is progressing rapidly in the laboratory. The results are very relevant to our desire to selectively and safely destroy senescent cells, and the real challenge here lies in the reliable identification of senescent cells. As noted last year, we need a robust way of identifying senescent cells; that is the one vital ingredient not yet in place that will allow all that cell-killing expertise present in the cancer research community to be turned to senescent cells.

"It was only a matter of time, however, and here we have a first attempt at a targeting mechanism for senescent cells - which is exciting news if it pans out and the chemical signature of senescence that the researchers focused on here is a good distinguishing mark throughout the different tissue types in the body:

"The nanodevice that we have developed consists of mesoporous nanoparticles with a galactooligosaccharide outer surface that prevents the release of the load and that only selectively opens in degenerative phase cells or senescent cells. The proof of concept demonstrates for the first time that selected chemicals can be released in these cells and not in others ... The researchers have evaluated the utility of the new nanodevices in primary cell cultures derived of patients with accelerated aging syndrome dyskeratosis congenita (DC). Such cultures show a high percentage of senescence characterized by elevated levels of beta-galactosidase activity, an enzyme characteristic of senescent state. 'The aging cells overexpress this enzyme so we have designed nanoparticles that open when detected and release their contents in order to eliminate senescent cells, prevent deterioration or even reactivate for their rejuvenation'."

A SPECULATIVE ORDER OF ARRIVAL FOR REJUVENATION BIOTECHNOLOGIES

Rejuvenation of the old will require a toolkit of various therapies and approaches, each of which repairs one of the forms of low-level biochemical damage that cause aging. These therapies must all be developed, as any one part of aging can still kill people, but what can we say about the likely order of their arrival?

https://www.fightaging.org/archives/2012/10/a-speculative-order-of-arrival-for-important-rejuvenation-therapies.php

"Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field.

"While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering."

VIDEO: BASIL GELPKE TALKS WITH AUBREY DE GREY

You'll find an interview with Aubrey de Grey and a trailer for Basil Gelpke's Human 2.0 in the Fight Aging! post linked below:

https://www.fightaging.org/archives/2012/10/aubrey-de-grey-on-longevity-science.php

"The human being will be the first species able to understand its own blueprint. The rapidly increasing knowledge of genetics, nanotechnology, robotics, and AI will dwarf everything philosophers, scientists, science fiction writers and other visionaries have ever conceived. Human life without disease and possibly even without death doesn't seem impossible anymore."

ON ZINC TRANSPORT DYSREGULATION WITH AGING

While the following post does discuss zinc metabolism in aging, it should be taken more in the way of an explanation as to why Fight Aging! steers clear of any discussion of the intersection between supplements and aging. It requires a page of preamble and afterword to be able to do so sensibly while ensuring that the right point is being made:

https://www.fightaging.org/archives/2012/10/on-zinc-transport-dysregulation-with-aging.php

"I don't often talk about anything related to the overlap between supplements and aging. For one, that entire industry is irrelevant given the scope of regenerative medicine and rejuvenation biotechnology: the future is deliberately designed and targeted medical technologies, not the lingering remnants of past medical practices influenced by oral fixation and magical thinking. You can't fix anything of significance in human aging by digging around for found compounds to stick into your mouth - that is characteristic of the just-about-up-to-dealing-with-infections medicine of the last millennium, and the sooner this model ceases to dominate the public imagination the better.

"Secondly, there are any number of vocal resources out there that talk about nothing but naturally occurring things that you can stick into your mouth. Many of them want to sell you those naturally occurring things, and of those folk a sizable contingent spend their time making loud and unsupported claims with regard to their products and human aging. Unfortunately there is so much money in that business that sense and ethics largely fled a long time ago.

"Lastly, nothing you can presently buy, consume, or wear is anywhere near as effective as either exercise or calorie restriction when it comes to health over the long term. Science tells us that much, with a great weight of evidence, and anyone claiming otherwise has a tall hill indeed to climb to make any sort of a case. They try nonetheless, day in and day out, and merchant voices often outweigh those of the scientific community in our popular culture when it comes to the relationship between people, medicine, and aging.

"So I don't often talk about anything related to supplements. It isn't productive. Still, occasionally research does show up to suggest that there might be meaningful benefits to some form of therapy using a common supplement or food item. It's pretty rare, however - next to nonexistent. The only one springing to mind right this instant is the evidence suggesting that the body processes the essential amino acid luceine increasingly poorly with aging. This contributes to the muscle wasting of sarcopenia, but, unlike nearly all such issues, can be staved off by adding more luceine to the diet.

"Again, let me emphasize that this sort of situation is rare. It is almost never the case that a specific progressive failure in the body's biochemistry can be ameliorated by sticking more of something related to the failure into your mouth. Biology is far more complex than that - imagining that you can affect a specific portion of your biochemistry in some desired way by consuming one of the compounds involved in a reaction somewhere in the process is basically a form of magical thinking.

So that all said as a sort of preamble, let me point you to a study on zinc-related mechanisms that's presently doing the rounds ... If a progressively disarrayed zinc metabolism does impact inflammation and immune function in a fairly general way, one would expect to see some beneficial effect on life span from suitably zinc-fortified diets. You might look at another recent paper for an example of researchers pumping extra zinc into laboratory animals to see what happens - I'm sure that there's much more out there from past decades if you care to go digging.

"In any case, I note this research for its rarity rather than its potential utility. At the end of the day, how much zinc you put into your diet will not swing your life span by anywhere near as much as even a mediocre level of progress towards biotechnologies that can repair the root causes of aging. As a culture, we need to tear ourselves away from the propaganda of the supplement industry and the fascination with dietary tinkering: none of that will save lives or meaningfully deal with the fact that we're all aging to death.

"Biotechnology is where we must look to the future of medicine: gene therapies, ways to precisely alter specific cellular components, targeted nanoparticles to remove senescent cells, stem cell engineering, tailored bacterial enzymes to break down unwanted intracellular waste products - these and many similar lines of research are the future and the path to living in good health for many more years than were available to our ancestors."

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

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LATEST HEADLINES FROM FIGHT AGING!

NOTING PROGRESS IN ARTIFICIAL CORNEA DEVELOPMENT
Friday, October 5, 2012
https://www.fightaging.org/archives/2012/10/noting-progress-in-artificial-cornea-development.php
The development of artificial replacements proceeds in parallel with tissue engineering as a way to build replacement parts for damaged corneas. Here, publicity materials tout recent progress in artificial corneas: "ArtCornea is based on a polymer with high water-absorbent properties. [Researchers] have added a new surface coating to ensure anchorage in host tissue and functionality of the optic. The haptic edge was chemically altered to encourage local cell growth. These cells graft to the surrounding human tissue, which is essential for anchorage of the device in the host tissue. The researchers aimed to enlarge the optical surface area of the implant in order to improve light penetration beyond what had previously been possible ... Once ArtCornea is in place, it is hardly visible, except perhaps for a few stitches. It's also easy to implant and doesn't provoke any immune response The specialists have also managed to make a chemically and biologically inert base material biologically compatible for the second artificial cornea, ACTO-TexKpro. [They] achieved this by selectively altering the base material, polyvinylidene difluoride, by coating the fluoride synthetic tissue with a reactive molecule. This allows the patient's cornea to bond together naturally with the edge of the implant, while the implant's inner optics, made of silicon, remain free of cells and clear. The ACTO-TexKpro is particularly suitable as a preliminary treatment, for instance if the cornea has been destroyed as a consequence of chronic inflammation, a serious accident, corrosion or burns. TexKpro and ArtCornea [were] first tested by the doctors in the [laboratory] in vivo in several rabbits. After a six month healing process, the implanted prostheses were accepted by the rabbits without irritation, clearly and securely anchored within the eye. Tests carried out following the operation showed that the animals tolerated the artificial cornea well. [Clinical trials will] soon commence at the Eye Clinic Cologne-Merheim."

A CRYONICS PHOTO ESSAY AT WIRED
Friday, October 5, 2012
https://www.fightaging.org/archives/2012/10/a-cryonics-photo-essay-at-wired.php
Wired is running a photo essay on cryonics, the low-temperature preservation technique that intends to preserve the structure of the mind sufficiently well for patients to be restored to life by future technology: "The Prospect of Immortality is a six-year study by UK photographer Murray Ballard, who has traveled the world pulling back the curtain on the amateurs, optimists, businesses and apparatuses of cryonics. "It's not a large industry," says Ballard, who visited the Alcor Life Extension Foundation in Phoenix, Arizona; the Cryonics Institute in Detroit, Michigan; KrioRus in Moscow, Russia; and Suspended Animation Inc in Boytan Beach, Florida; among others. Cryonics is the preservation of deceased humans in liquid nitrogen at temperatures just shy of its boiling point of -196°C/77 Kelvin. Cryopreservation of humans is not reversible with current science, but cryonicists hypothesize that people who are considered dead by current medical definitions may someday be recovered by using advanced future technologies. Stats are hard to come by, but it is estimated there are about 2,000 people signed up for cryonics and approximately 250 people currently cryopreserved. Over 100 pets have also been placed in vats of liquid nitrogen with the hopes of a future recovery."

SHARED MECHANISMS FOR LONGEVITY VIA CALORIE RESTRICTION AND AC5 KNOCKOUT
Thursday, October 4, 2012
https://www.fightaging.org/archives/2012/10/shared-mechanisms-for-longevity-via-calorie-restriction-and-ac5-knockout.php
One of the handful of genetic alterations shown to extend life in mice is removal of adenylyl cyclase 5 (AC5). Researchers have noted in the past that this seems to share mechanisms with the longevity induced by calorie restriction - indeed, it is suspected that many of the varied known ways of altering laboratory animals to extend healthy life are in fact different methods to activate the same few base changes in metabolism. Here is another paper on this topic: "Adenylyl cyclase type 5 knockout mice (AC5 KO) live longer and are stress resistant, similar to calorie restriction (CR). AC5 KO mice eat more, but actually weigh less and accumulate less fat compared to [wild type] mice. CR applied to AC5 KO result in rapid decrease in body weight, metabolic deterioration and death. These data suggest that despite restricted food intake in CR, but augmented food intake in AC5 KO, the two models affect longevity and metabolism similarly. To determine shared molecular mechanisms, mRNA expression was examined genome-wide for brain, heart, skeletal muscle and liver. Significantly more genes were regulated commonly rather than oppositely in all the tissues in both models, indicating commonality between AC5 KO and CR. Gene Ontology analysis identified many significantly regulated, tissue-specific pathways shared by the two models, including sensory perception in heart and brain, muscle function in skeletal muscle, and lipid metabolism in liver. Moreover, when comparing gene expression changes in the heart under stress, the glutathione regulatory pathway was consistently upregulated in the longevity models but downregulated with stress. In addition, AC5 and CR shared changes in genes and proteins involved in the regulation of longevity and stress resistance, including Sirt1, ApoD and olfactory receptors in both young and intermediate age mice. Thus, the similarly regulated genes and pathways in AC5 KO and CR [suggest] a unified theory for longevity and stress resistance."

REPORTING ON A RECENT PRESENTATION BY AUBREY DE GREY
Thursday, October 4, 2012
https://www.fightaging.org/archives/2012/10/reporting-on-a-recent-presentation-by-aubrey-de-grey.php
SENS Foundation cofounder Aubrey de Grey is a tireless advocate for engineering the end of aging, and steers the work taking place on the foundations of rejuvenation biotechnology at the Foundation's research center and in a halo of allied laboratory groups. He gives a great many presentations on the work and goals of the Foundation in the course of any given year, and here is an article noting one such recent event at Princeton University: "The seminar, called "The Science and Ethics of Eliminating Aging," was sponsored by the University's Center for Human Values and chaired by bioethics professor Peter Singer. De Grey presented his research on anti-aging therapy, promoted his vision for a world in which humans do not experience the negative effects of aging and evaluated the benefits of and objections to this future society. De Grey began his presentation by defining aging. He said his foundation does research on ways to limit damages done to the human body by natural metabolic processes and that he hopes the research will allow them to identify a physical state in which one could perpetually "look and feel and function like a young adult." There are seven specific types of damage aging does to the body, de Grey noted. Although solutions to these have not been reached, he described a scientific breakthrough his group achieved several months ago; a study they had performed showed increased viability of cells in a culture, which he said could have implications for stopping the damage that causes cardiovascular disease. De Grey then described the feasibility and societal benefits of successful development of anti-aging technology. He said his research suggests a "50-50 chance of developing these therapies within the next 25 years to a level of sophistication that will confer ... robust human rejuvenation." On a slide comparing two pictures, de Grey simply summarized his views on the positives and negatives of anti-aging: one of young people at play labeled "Fun" and another of a sickly senior citizen labeled "Not Fun." Therefore, he argued that everyone - from biologists to journalists to ordinary citizens practicing advocacy - should work to achieve successful anti-aging solutions. Finally, de Grey suggested that a society in which people live indefinite life spans would have a higher quality of life. He noted that critics argue that indefinite life spans would lead to overpopulation and that living forever might not be desirable. However, those are not reasons to halt research into anti-aging solutions and those are ethical questions best decided by future generations, he said. "Even if we did have a problem [arising from anti-aging development] and humanity had a choice to make ... that's a choice humanity of the future is entitled to make for itself rather than having that choice imposed on it by our not choosing to develop these therapies," de Grey said."

TELOMERE LENGTH ALONE IS NOT A GOOD BIOMARKER OF AGING
Wednesday, October 3, 2012
https://www.fightaging.org/archives/2012/10/telomere-length-alone-is-not-a-good-biomarker-of-aging.php
Different people age at different rates. Efforts have long been underway to find a reliable, effective way to measure physiological age in order to relate that to remaining life expectancy and mortality rate. Without a biomarker of aging that can be easily measured, it will remain very challenging to evaluate future therapies that intervene in the aging process: how do you know whether a particular medical technology worked, or whether it worked better or worse than a competing therapy? The wait and see approach for determining effects on life span requires years and millions of dollars in mouse studies, while finding a definitive answer in humans is out of the question on the time scales involved here. The whole field of medicine will be transformed over the next two decades, but it would take much longer than that to even begin to answer simple questions as to effects of prospective rejuvenation therapies in humans. Telomeres are protective caps at the end of chromosomes. Their length is determined by a number of dynamic lengthening and shortening processes, but on average tends to erode with age or ill health. Thus telomere length has been proposed as a biomarker of aging, but as this paper shows simple measures of average telomere length are not all that useful in and of themselves: "The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure. Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites. Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area." In this context, you may want to look at another recent paper where the authors suggest that more sophisticated measures of telomere dynamics, such as counting changes in the proportion of very short telomeres, are in fact good biomarkers of aging.

MANIPULATING IMMUNE RESPONSE TO BOOST NERVE REGENERATION
Wednesday, October 3, 2012
https://www.fightaging.org/archives/2012/10/manipulating-immune-response-to-boost-nerve-regeneration.php
One of the reasons that nerves regenerate poorly has to do with the way in which the immune system responds to traumatic injury. In essence its behavior tends towards the formation of scar tissue that blocks nerve regrowth rather than allowing for regeneration. With greater understanding of the underlying mechanisms, researchers can try to change this state of affairs: "By altering activity of the macrophage cells that respond to injuries, researchers dramatically increased the rate at which nerve processes regrew. Influencing the macrophages immediately after injury may affect the whole cascade of biochemical events that occurs after nerve damage, potentially eliminating the need to directly stimulate the growth of axons using nerve growth factors. Macrophages can exist in several different phenotypes depending on the signals they receive. Among the macrophage phenotypes are two classes - M2a and M2c - that encourage healing. [The] research team used an interleukin 4 (IL-4) cytokine to convert macrophages within the animal model to the "pro-healing" phenotypes. They placed a gel that released IL-4 into hollow polymeric nerve guides that connected the ends of severed animal sciatic nerves that had to grow across a 15 millimeter gap to regenerate. The IL-4 remained in the nerve guides for 24 hours or less, and had no direct influence on the growth of nerve tissue in this short period of time. Three weeks after the injury, the nerve guides that released IL-4 were almost completely filled with re-grown axons. The treated nerve guides had approximately 20 times more nerve regeneration than the control channels, which had no IL-4-treated macrophages. Research is now underway to develop the technique for determining how soon after injury the macrophages should be treated, and what concentration of IL-4 would be most effective."

NOTES ON ALCOR'S 2012 STRATEGY MEETING
Tuesday, October 2, 2012
https://www.fightaging.org/archives/2012/10/notes-on-alcors-2012-strategy-meeting.php
Cryonics provider Alcor is becoming more transparent and communicative under CEO Max More, which I see as a good thing. One of the long-term challenges faced by Alcor (and all cryonics providers, for that matter) relates to the common model for customer membership and setting prices, insofar as that is impacted by increasing costs brought on by inflation that takes place over the decades that elapse between a customer initially signing up and later being cryopreserved. It's hard to solve that problem gracefully without a great deal of dialog with the customer community, as it basically boils down to either losing a bunch of money, thus endangering the business, or asking customers to pay more than they originally agreed to: "The 2012 Strategic Meeting took place from Friday September 7 until Sunday September 9. All Alcor directors attended in person, as did Alcor president Max More. The Strategic Meeting is the annual, intensive review of the organizations priorities and performance. You will find a more extensive discussion of several of the outcomes in a forthcoming issue of Cryonics magazine, but here are the main resolutions and priorities on which agreement was reached: ... As minimum requirements for funding of cryopreservation inevitably go up over time, members who did not take out insurance well over the minimum of the day - or who do not regularly add to their savings in the form of a trust or other fund reserved for cryopreservation - may find it difficult to meet new, higher minimums. For older members, adding to life insurance may be too expensive or not an option. Other assets may be illiquid yet substantial, real estate being a common example. At the meeting, the board and president discussed alternative funding methods and resolved further to pursue possible options. If cryonics is to become more widely accepted in the general scientific community, we need to add to existing evidence for the effectiveness of our procedures. One way to do this is to gather more data during all stages of stabilization, transport, and cryoprotection. We can also gather evidence of the quality and effectiveness of brain perfusion and structural preservation by routine CT scanning of neuro patients and by conducting biopsies of spinal cord and possibly other samples for all patients. The board expressed general support for carefully moving forward with this, ensuring that members understand what we propose to do."

SEVERAL VITAL CELL POPULATIONS COULD GROW IN LYMPH NODES
Tuesday, October 2, 2012
https://www.fightaging.org/archives/2012/10/several-vital-cell-populations-could-grow-in-lymph-nodes.php
A replacement liver (or thymus or other organ) doesn't necessarily have to look like or be structured in the same way as the original - it just has to do the same job as the original. This is perhaps more obvious in the development of wholly artificial electromechanical organs than for tissue engineering, but it's still the case there as well. Here is some interesting research that illustrates this point. In some cases specialized cell populations within an organ's structure are the important component of that organ, and thus to replace the organ's functions it is sufficient for those cells to exist in some useful location: "Lymph nodes can provide a suitable home for a variety of cells and tissues from other organs, suggesting that a cell-based alternative to whole organ transplantation might one day be feasible. [Researchers] showed for the first time that liver cells, thymus tissue and insulin-producing pancreatic islet cells, in an animal model, can thrive in lymph nodes despite being displaced from their natural sites. In the study, [researchers] tested the possibility of using lymph nodes, which are abundant throughout the body and have a rich blood supply, as a new home for cells from other organs in what is called an "ectopic" transplant. They injected healthy liver cells from a genetically-identical donor animal into lymph nodes of mice at various locations. The result was an enlarged, liver-like node that functioned akin to the liver; in fact, a single hepatized lymph node rescued mice that were in danger of dying from a lethal metabolic liver disease. Likewise, thymus tissue transplanted into the lymph node of mice that lacked the organ generated functional immune systems, and pancreatic islet cell transplants restored normal blood sugar control in diabetic animals. "Our goal is not necessarily to replace the entire liver, for example, but to provide sufficient cell mass to stabilize liver function and sustain the patient's life. That could buy time until a donor organ can be transplanted. Perhaps, in some cases, ectopic cell transplantation in the lymph node might allow the diseased organ to recover.""

WHAT FAILURE WILL LOOK LIKE: A PILL FOR HEALTHY AGING
Monday, October 1, 2012
https://www.fightaging.org/archives/2012/10/what-failure-will-look-like-a-pill-for-healthy-aging.php
There is a forking of the way in aging research, and it matters greatly which path comes to dominate: whether the mainstream (a) continues as in the past, ignoring all mention of engineered longevity and doing nothing more than investigating aging, (b) focuses on limited ways to slow aging, largely in the name of compression of morbidity while trying to minimize talk of extended life spans, or (c) works on ways to reverse and repair the root causes of aging, with the explicit goal of extending healthy and maximum human life spans. Of these options only (c) will greatly help those of us who will need ways to repair the damage caused by aging a few decades from now. Ways to slow aging do little for people who are already old. Unfortunately very little of the research community is presently interested in or working on repair of the root causes of aging - though that faction is larger today than in the past, thanks to persistent advocacy and organizations like the Methuselah Foundation and SENS Foundation. This article shows us what failure will look like: what the end goal will be some decades from now if the "only work to slow aging" and "don't talk about extending life" factions continue to dominate the research community: "Dame Linda Partridge, a geneticist at University College London, claimed drugs will soon be available which can lower the risk of diseases like cancer and dementia by tackling the root cause - age itself. Rather than promising immortality, taking the drugs from middle age or earlier could dramatically shorten the period of illness and frailty that we typically experience before we die. Speaking at the EMBO life sciences meeting in Nice, France this week Dame Linda said several existing drugs have already been shown to have unexpected and welcome side effects, such as aspirin which reduces the risk of cancer. Other therapies will be produced that mimic the effects of a severely restricted diet, which animal studies suggest can protect against a host of age-related conditions including heart disease and diabetes, she said. Speaking after her keynote lecture, she said: "One obvious approach in trying to deal with the very rapidly increasing incidence of age related diseases is to tackle the underlying aging process itself, because it is the major risk factor. What we want is, rather than a lingering period of ill health, to have a fairly sudden death when it comes. We are not talking about immortality, we are trying to get rid of that period of ill health that people get towards the end of their lives, to hold off age related disease for longer.""

INROADS INTO MAKING OLD IMMUNE CELLS MORE RESPONSIVE
Monday, October 1, 2012
https://www.fightaging.org/archives/2012/10/inroads-into-making-old-immune-cells-more-responsive.php
One of the reasons that the adaptive immune system declines with age is that too much of its limited resources become devoted to uselessly chasing persistent herpesviruses like CMV. But there are other mechanisms at work too - not just a depletion of cells ready to act, but a decline in these cells' ability to act. So we have research such as this, in which scientists chase down age-related molecular mechanisms that hold back the effectiveness of immune cells, and try to reverse them: "Circulating T-helper cells fall into two broad categories. "Naïve" T-helper cells have never encountered an antigen before (as in the case of, say, a rare or emerging pathogen or a new vaccine), but are capable of wheeling into action once they do. It takes a week or two to reach full tilt. "Memory" T-helper cells have previously been exposed to an antigen. These cells are long-lived and narrowly fixed on that particular antigen. They can rapidly transition to an activated state should the same antigen ever cross their path again. That's why prior exposure - through infection or a vaccine - renders us more resistant. [Researchers] showed that faulty regulation in memory T-helper cells, due to aging-related increased levels of a protein called DUSP4, inhibits the activation of those cells, with their consequent failure to ignite a good B-cell (antibody-producing) response. This time around, the investigators uncovered a similar effect with a related protein, DUSP6, on naïve T-helper cells. In test tubes, they compared blood cells drawn from people ages 20-35 versus 70-85 in response to stimulation. In naïve T-helper cells (but not in memory cells), there were age-associated differences in a specific chain of biochemical events involved in the cells' activation, proliferation and differentiation. Laboratory tests showed that the culprit behind the cells' fecklessness in older people was DUSP6, [with levels that were] much higher in older people's naïve T-helper cells. Further experimentation revealed that DUSP6's increase in aging naïve T-helper cells was caused by an age-associated easing up on a brake pedal called miR-181a, one among hundreds of small molecules made of RNA (called microRNA) that regulate proteins' production. ... Artificially boosting miRNA-181a levels in naïve human T cells caused DUSP6 levels to plummet, commensurately increasing those cells' readiness to activate on exposure to a given dose of influenza vaccine. In contrast, artificially increasing the levels of DUSP6 blocked the beneficial effects of heightened miR-181a levels."

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