Fight Aging!

FIGHT AGING! NEWSLETTER
April 30th 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

- An Interview with Michael Batin
- Conflating Aging and Degeneration
- The FDA is a Destructive Force
- Discussion
- Latest Headlines from Fight Aging!

AN INTERVIEW WITH MICHAEL BATIN

The 2nd International Conference on the Genetics of Aging and Longevity was held this past week in Moscow, well-attended by the aging research community. Here is an interview, machine translated from Russian:

https://www.fightaging.org/archives/2012/04/an-interview-with-michael-batin.php

"Earlier this month, the Moscow News ran an interview with Michael Batin, one of the [conference] organizers. His views are representative of the Russian community, whose members tend to be forthright and direct when it comes to the end goals of longevity science: to defeat aging entirely, banish the suffering it causes, and usher in an era of ageless humans. More power to them - we could do with a lot more of that sort of outspoken advocacy here in the Anglosphere.

"Q: What is the real goal that we set ourselves right now? Can you say, talk about extending the life of ten years from now?

MB: In ten years? It is not even present, and yesterday. It has long been proven that reducing caloric intake [and even] just a healthy lifestyle [lead to a longer life]. Our goal is different - a victory over an aging, it is by and large the whole purpose of medical science. After all, if you think about all of the doctors [dedicated to the] prolongation of life, the estrangement of death. A person does not want to die right now, well, anti-aging does not differ fundamentally, it is also the struggle with death.

Q: So you're talking about immortality?

MB: Yes. This is the ultimate goal. In the coming ten years, you can raise the life expectancy [to] 150 years, with adequate [resources and large enough research community]. If, for example, to do research megaproject like the American lunar program. And if we know in ten years that will live more than a hundred years, this will give us more time to find a way to further extend [life].

Q: But how? Are there any pills?

MB: If you're talking about a miracle pill, then, of course not. Aging depends on many factors, and is now the main problem is just that we do not know them all. And the proposed mega-project just involves a systematic search for the causes of aging.

Q: And it's all in the mega-project? [It's] going to cost [a] quite impossibly high sum.

MB: But now we are spending huge amounts of money on arms - you've seen defense spending in Russia? - And do not invest in [biogerontology], fundamental research on the causes of aging. Even in the U.S., [where] gerontology takes a billion dollars, [that is] their total spending, of that billion is spent on Alzheimer's disease, [on] geriatrics, and [only a small fraction of it on] the fundamental work on finding the root causes of aging."

CONFLATING AGING AND DEGENERATION

Aging absent degeneration would be a wonderful thing:

https://www.fightaging.org/archives/2012/04/conflating-aging-and-degeneration.php

"There's a lot to be said for aging. The passage of years offers many opportunities to master favored skills, figure out solutions to the issues and upsets of youth, earn the resources and connections needed for true self-sufficiency and confidence, and much more. You can build a great life, given just the time to work on it and a modicum of common sense - and then keep on building atop the foundation of that great life. Humans age like distillates: it can just keep getting better. But of course there is the matter of degeneration and death, of disease and decrepitude. The fact that older people are generally happier, more secure, and more confident despite what happens to the body with age is a testament to just how good being aged is. That the majority evaluate their position as far superior to that of earlier years despite the increasing corrosion of the body and the ticking away of time remaining is a powerful statement.

"On this topic, I should note that over the years an unfortunately large number of apologists for aging have become somewhat dazzled by the good parts of the package, to the point at which they are unwilling to talk about picking apart aging and degeneration, or trying to radically change aging through medical technology. To their view, the world is what it is, and we should just focus on the positives and suffer the negatives with dignity. Not that that last point is easy at all - there is no dignity in the failing of the body and mind, only horrors that the dominant voices of this society seem to have chosen to try to close away behind the curtains.

"It is both somewhat strange and somewhat understandable to find so many conservatives - in the dictionary definition of the word, not the political definition - in an age of rampant, ongoing, omnipresent change. Those who benefit the most from technological progress, and consequent decade by decade shifts in the minutiae of the human condition, nonetheless adopt positions based on the idea that what presently exists will continue to exist as-is into the future. It's denial, it's letting the ape inside drive - the ape who really, really, doesn't like change or upsets to the present carefully constructed social hierarchy, no matter how beneficial it might be.

"Being aged is great, but it's just plain dumb to try to turn that into an argument that being sick, lessened, in agony, and driven mad is also great. Medicine will be able to remove all of these ugly aspects of old age, provided that we work hard enough and fund the right sort of research and development to a sufficient degree. The people who paint on sunny smiles and say that nothing will ever change are only helping to hold back that future."

THE FDA IS A DESTRUCTIVE FORCE

We would be so much further along in applied biotechnology if not for the perverse engines of regulation that hold back progress in much of the world:

https://www.fightaging.org/archives/2012/04/the-fda-is-a-destructive-force.php

"The employees and appointees of the US Food and Drug Administration have caused an incredible destruction of value and progress over the time that the agency has existed. Their regulatory policies become ever more onerous with each passing year, as unaccountable bureaucrats follow their incentives: nothing good can happen to their careers as a result of approving new technologies, and nothing bad tends to happen to their careers as a result of making it really, really hard to bring new medicine to the clinic. So of course you wind up with an organization whose members collectively pay nothing more than lip service to their declared mission, while working to make sure that medicine stays moribund in a slow-motion stasis. This is most evident in the cancer research community, largely because of its size, but it applies just as evenly across all forms of medicine:

"A 2010 study in the Journal of Clinical Oncology by researchers from the M.D. Anderson Cancer Center in Houston, Texas found that the time from drug discovery to marketing increased from eight years in 1960 to 12 to 15 years in 2010. Five years of this increase results from new regulations boosting the lengths and costs of clinical trials. The regulators aim to prevent cancer patients from dying from toxic new drugs. However, the cancer researchers calculate that the delays caused by requirements for lengthier trials have instead resulted in the loss of 300,000 patient life-years while saving only 16 life-years.

"To add to this picture, you must also see incumbent Big Pharma entities and their executives and lobbyists - a deeply enmeshed network of regulatory capture. They are far more willing to use the current system as a weapon to suppress disruptive innovation in their industry than to be a source of innovation themselves. So it goes, just as in any other heavily regulated market. The strategic goals of the major players wind up having very little to do with creating beneficial change, and everything to do with keeping things the same as they are now.

"Though the United States urgently needs new treatments for common illnesses such as heart disease, stroke, and diabetes, the nation's system for drug approval discourages innovation and investment, especially for our most pressing public health challenges. In this paper, we find that the main culprit is the high cost of Phase III clinical trials, which are required for FDA approval of most drugs. We examined drug development in four major public health areas and discovered that for any given drug on the market, typically 90 percent or more of that drug's development costs are incurred in Phase III trials. These costs have skyrocketed in recent years, exacerbating an already serious problem."

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!

RESEARCHER STEVEN AUSTAD WRITES A BIWEEKLY COLUMN ON AGING SCIENCE
Friday, April 27, 2012
https://www.fightaging.org/archives/2012/04/researcher-steven-austad-writes-a-biweekly-column-on-aging-science.php
This seems like an interesting marker of public awareness of aging science; one of the noted researchers in the field recently started on a biweekly column for a local paper. Links to the columns published to date can be found on this page: "In my last column I discussed something we all know intuitively: Generally speaking, larger species of animals live longer than smaller species and this pattern extends even to whales that live more than 200 years. Are there dramatic exceptions to this rule - like people, for instance? Think of other mammals about our size, such as deer or mountain lions or seals. Don't we live longer than they do? The answer is, 'Yes, we do.' Humans live about five times as long as the average mammal of the same size, which makes us pretty special - but not as special as bats. Texas is bat country, as anyone who has watched millions of bats boil out of Bracken Cave or from under Austin's Congress Avenue Bridge can verify. What many people don't realize is how long bats live. For their size, bats are the longest-lived mammals by far, living up to 10 times as long as an average mammal of similar size. ... Think about this for a second. Your dog or cat, eating the best food science can provide, protected from predators and the elements and vaccinated against all sorts of diseases, is doing well to reach 15 to 20 years of age. By comparison, in order for a bat in the wild to survive it must catch its own prey, elude predators, resist climatic extremes, and avoid a wide range of infectious diseases. Yet despite these challenges, bats can live twice as long as your pampered pet." Current thinking on bat longevity looks to be similar to theories on naked mole rat longevity - it has to do with resistance of cell membranes (and especially mitochondria) to oxidative damage, otherwise known as the membrane pacemaker hypothesis of aging. This is thought to have developed in bats, and in birds, in respond to the metabolic demands of flight.

EXAMINING MITOCHONDRIAL DNA DAMAGE IN DETAIL
Friday, April 27, 2012
https://www.fightaging.org/archives/2012/04/examining-mitochondrial-dna-damage-in-detail.php
Damage to mitochondrial DNA contributes to aging, and mitochondrial function is in general influential upon aging - damage causes harm by preventing the production of protein machinery vital to mitochondrial activity, which is the start of a long process that sees cells overtaken by dysfunctional mitochondria, and exporting their dysfunction to surrounding tissue by emitting harmful reactive molecules. There are numerous different sorts of DNA damage, however. Point mutations, for example, have been shown to do little to aging. Deletions, where whole reaches of DNA are knocked out, are a different story, and here researchers are investigating how this form of DNA damage varies between species: "Deletion mutations within mitochondrial DNA (mtDNA) have been implicated in degenerative and aging related conditions, such as sarcopenia and neuro-degeneration. While the precise molecular mechanism of deletion formation in mtDNA is still not completely understood, genome motifs such as direct repeat (DR) and stem-loop (SL) have been observed in the neighborhood of deletion breakpoints and thus have been postulated to take part in mutagenesis. In this study, we have analyzed the mitochondrial genomes from four different mammals: human, rhesus monkey, mouse and rat ... Our analysis revealed that in the four species, DR and SL structures are abundant and that their distributions in mtDNA are not statistically different from randomized sequences. However, the average distance between the reported age associated mtDNA breakpoints and their respective nearest DR motifs is significantly shorter than what is expected of random chance in human and rhesus monkey, but not in mouse and rat, indicating the existence of species specific difference in the relationship between DR motifs and deletion breakpoints. In addition, the frequencies of large DRs tend to decrease with increasing lifespan among the four mammals studied here, further suggesting an evolutionary selection against stable mtDNA misalignments associated with long DRs in long-living animals."

FURTHER WORK ON EPIGENETIC CHANGES THAT OCCUR WITH AGING
Thursday, April 26, 2012
https://www.fightaging.org/archives/2012/04/further-work-on-epigenetic-changes-that-occur-with-aging.php
Via ScienceDaily: researchers "have identified a group of 'aging' genes that are switched on and off by natural mechanisms called epigenetic factors, influencing the rate of healthy aging and potential longevity. The study also suggests these epigenetic processes - that can be caused by external factors such as diet, lifestyle and environment - are likely to be initiated from an early age and continue through a person's life. The researchers say that the epigenetic changes they have identified could be used as potential 'markers' of biological aging and in the future could be possible targets for anti-aging therapies. ... the study looked at 172 twins aged 32 to 80 from the TwinsUK cohort. The researchers looked for epigenetic changes in the twins' DNA, and performed epigenome-wide association scans to analyze these changes in relation to chronological age. They identified 490 age related epigenetic changes. They also analysed DNA modifications in age related traits and found that epigenetic changes in four genes relate to cholesterol, lung function and maternal longevity. To try to identify when these epigenetic changes may be triggered, the researchers replicated the study in 44 younger twins, aged 22 to 61, and found that many of the 490 age related epigenetic changes were also present in this younger group. The researchers say these results suggest that while many age related epigenetic changes happen naturally with age throughout a person's life, a proportion of these changes may be initiated early in life."

INSIGHTS INTO AGING FROM THE STUDY OF FLIES
Thursday, April 26, 2012
https://www.fightaging.org/archives/2012/04/insights-into-aging-from-the-study-of-flies.php
An open access review paper looks at how the study of fly aging has informed the life sciences: "it is likely that not all senescent physiological changes revealed in flies can be simply translated to humans. However, flies and humans often show very similar age-related physiological phenotypes suggesting that at least some of the basic biological properties and mechanisms that regulate longevity are conserved amongst species. ... It is well-known that advances in medicine and health care have significantly contributed to increased longevity in humans over the last 100 years. There is also a clear trend toward increased life expectancy including an increase in the numbers of people living to an advanced age and the number of people with chronic age-related diseases. These trends emphasize the need to understand the genetic and physiological factors underlying biological aging and particularly, those that promote healthy aging. ... there are three ways to extend lifespan: increasing early survival rate, increasing late survival rate, or delaying senescence. Remarkably, the first two do not affect basic aging processes. For example, the first one leads to a significant increase in mean but not maximum lifespan, while the second one leads to change in a maximum but not mean lifespan. Delayed senescence, in turn, leads to a significant increase in both the mean and maximum lifespan. ... This raises the question as to whether healthspan and delayed senescence are inter related. As stated above, while many genes have been shown to extend lifespan, these may have little or no ability to delay physiological senescence. In other words, the period of functional disability before death may increase despite the fact that the total duration of life is increased. Thus, the search for appropriate biomarkers applicable to monitor functional senescence is highly important with regards to healthy aging and age-related diseases." These cautions are very much focused on the mainstream research goals of slowing the rate of aging through genetic and metabolic alterations; they have little relevance to efforts aimed at producing continuous repair of aging.

RAPAMYCIN AND OXIDATIVE STRESS IN ADULT STEM CELLS
Wednesday, April 25, 2012
https://www.fightaging.org/archives/2012/04/rapamycin-and-oxidative-stress-in-adult-stem-cells.php
Following on from research into the mechanisms of rapamycin released earlier this month, here is more on the way it might generate its benefits to longevity in laboratory mammals: "Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescence in vitro and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age. To test our hypothesis, we exposed mice to rapamycin and then examined the transcriptome of their spermatogonial stem cells (SSCs). Gene expression microarray analysis revealed that numerous oxidative stress response genes were upregulated upon rapamycin treatment ... When we examined the expression of these genes in 55-week-old wild type SSCs, their levels were significantly reduced compared to 3-week-old SSCs, suggesting that their downregulation is coincident with the aging process in adult stem cells. We conclude that rapamycin-induced stimulation of oxidative stress response genes may promote cellular longevity in SSCs, while a decline in gene expression in aged stem cells could reflect the SSCs' diminished potential to alleviate oxidative stress, a hallmark of aging."

LESS HAND OSTEOARTHRITIS IN LONGER-LIVED POPULATIONS
Wednesday, April 25, 2012
https://www.fightaging.org/archives/2012/04/less-hand-osteoarthritis-in-longer-lived-populations.php
Age-related diseases are among the more visible signs of accumulated biological damage that occurs over time - aging is damage. So we should expect to see less of all such conditions in longer lived populations, and here researchers demonstrate that point for osteoarthritis: "Previous studies have reported that centenarians escape the major age-related diseases. No studies on prevalence and severity of osteoarthritis (OA) in longevity population have previously been reported. Because OA is associated with morbidity and mortality, we hypothesized that radiographic hand OA would generally be less prevalent and would develop at a later age in longevity populations vs non-longevity populations. ... Longevity index was calculated as a ratio of the number of individuals aged [greater than] 90 years vs the number of people aged [greater than] 60, expressed per mil. A population with longevity index [greater than] 40 was considered as a longevity population. ... A significant difference in age standardized prevalence of hand OA was found between each pair of studied samples ... We observed that the pattern of radiographic hand OA in longevity populations differs from the pattern in non-longevity populations. On average, first joints with OA appear at an older age, and progression of hand OA [is] slower."

AN UPDATE ON CYTOGRAFT'S ENGINEERED BLOOD VESSELS
Tuesday, April 24, 2012
https://www.fightaging.org/archives/2012/04/an-update-on-cytografts-engineered-blood-vessels.php
Cytograft is one of many regenerative science ventures established in the past fifteen years, and a competitor in the space of growing blood vessels: "A lot of people were skeptical when two young California-based researchers set out more than a decade ago to create a completely human-derived alternative to the synthetic blood vessels commonly used in dialysis patients. Since then, they've done that and more. ... First the team created blood vessels from patients' own skin cells. Then, in June, the company announced that three dialysis patients had received the world's first lab-grown blood vessels made from skin cells from donors, which eliminates the long lead time needed for making vessels from a patient's own cells. And now Cytograft has developed a new technique for making human textiles that promises to reduce the production cost of these vessels by half. ... Cytograft's new approach builds on what already has been proved successful. In 2005, the team began extracting fibroblasts from patients' own skin, cultured those cells into thin sheets, rolled up those sheets, cultured them some more so that they would fuse together, and implanted the lab-grown cylindrical vessels. The vessel-growing process was lengthy, at about seven months, but, because the vessels were derived from the patients' own cells, the implants were easily accepted by the patients' bodies, and they held up to the rigors of dialysis, which requires repeated punctures with large-gauge needles. Then the researchers created allogeneic vessels - ones grown from donor cells - with the hope that they were laying the foundation for an off-the-shelf stockpile of 100 percent human replacement parts. ... By combining these two methods we could make something that is allogeneic, cheaper to produce, and that you could store forever, meaning that the clinician can pull it off the shelves whenever they want. If it is frozen and allogeneic, that is kind of the homerun."

STRUCTURES TO GUIDE NERVE REGROWTH
Tuesday, April 24, 2012
https://www.fightaging.org/archives/2012/04/structures-to-guide-nerve-regrowth.php
Via ScienceDaily: researchers "have developed a method of assisting nerves damaged by traumatic accidents to repair naturally, which could improve the chances of restoring sensation and movement in injured limbs. ... the team describes a new method for making medical devices called nerve guidance conduits or NGCs. The method is based on laser direct writing, which enables the fabrication of complex structures from computer files via the use of CAD/CAM (computer aided design/manufacturing), and has allowed the research team to manufacture NGCs with designs that are far more advanced than previously possible. Currently patients with severe traumatic nerve damage suffer a devastating loss of sensation and/or movement in the affected limb. The traditional course of action, where possible, is to surgically suture or graft the nerve endings together. However, reconstructive surgery often does not result in complete recovery. ... When nerves in the arms or legs are injured they have the ability to re-grow, unlike in the spinal cord; however, they need assistance to do this. We are designing scaffold implants that can bridge an injury site and provide a range of physical and chemical cues for stimulating this regrowth. ... Nerves aren't just like one long cable, they're made up of lots of small cables, similar to how an electrical wire is constructed. Using our new technique we can make a conduit with individual strands so the nerve fibres can form a similar structure to an undamaged nerve. ... Once the nerve is fully regrown, the conduit biodegrades naturally. The team hopes that this approach will significantly increase recovery for a wide range of peripheral nerve injuries."

AUBREY DE GREY TO DEBATE PROFESSOR COLIN BLAKEMORE
Monday, April 23, 2012
https://www.fightaging.org/archives/2012/04/aubrey-de-grey-to-debate-professor-colin-blakemore.php
Oxford University in the UK has a long tradition of formal public debating, and this week the Oxford University Scientific Society will be hosting a debate on longevity science between Aubrey de Grey of the SENS Foundation and Colin Blakemore former head of the Medical Research Council. This will be the first time that a fellow of the British biomedical establishment has risen to the challenge of describing publicly, in a forum where he can be challenged, why intervention against aging is not in fact medicine's most pressing priority - an area of debate in which the UK lags behind the US: "Oxford University Scientific Society is hosting a debate on Wednesday, 25th April, 2012. The debate will begin at 7pm local time (11am Pacific, 2pm Eastern) in the University of Oxford's Sheldonian Theatre; doors open 45 minutes earlier. Dr. Aubrey de Grey will propose the motion 'This house wants to defeat ageing entirely' and Professor Colin Blakemore will be opposing. The debate will be chaired and moderated by Professor Sir Richard Peto. This debate will address whether it is feasible and appropriate to consider ageing as a target of decisive medical intervention, raising the possibility of substantial extension of human lifespan. Aubrey de Grey is currently Chief Science Officer of SENS Foundation, a biomedical research charity that aims to develop, promote, and ensure widespread access to rejuvenation biotechnologies that address the diseases and disabilities of ageing. SENS Foundation aims to bring ageing under comprehensive medical control. Its research agenda consists of the application of regenerative medicine to ageing - not merely slowing the ageing clock, but resetting it to early adulthood. Colin Blakemore is Professor of Neuroscience at the University of Oxford Nuffield Department of Clinical Neurosciences. He is an expert in vision, development of the brain and neurodegenerative disease. He is active in communication of science and is president and adviser to several charities concerned with brain disorders. Prof. Blakemore was formerly Chief Executive of the Medical Research Council, the UK's largest public funder of biomedical research."

COMMENTARY ON THE NAYSAYERS
Monday, April 23, 2012
https://www.fightaging.org/archives/2012/04/commentary-on-the-naysayers.php
From the Daily Mail: "The Elixir of Youth has a terribly bad press. As soon as any scientist mentions that they have discovered a way of making fruit flies or worms or even mice live a bit longer and furthermore states that this might, just might, work in humans (after lots of tests, refinements, clinical trials and so on and anyway it is decades away at best, the caveats will be longer than the original research paper), you can bet a small vat of snake oil that the naysayers will soon weigh in. 'Who wants to live forever? Not me!' one curmudgeonly columnist will opine. 'What would a world be like with all those ancient people walking around, ugh!' will say another writer who, like the first, will have been commissioned mainly on the basis of their own rather advanced years. Because although the bizarre prejudice against anti-ageing research runs deep and wide, it doesn't quite run deep and wide enough for it to be all right for someone the right side of forty, say, to opine that the old really should shuffle off and leave the field clear. Up to now this has been pretty academic as anti-ageing potions have been little more than science fiction but, as an interesting feature in Nature magazine points out, it is beginning to look like a perfect storm of recent serendipitous discoveries and hard-won genetic advanced might - just might - put the holy grail of increasing human lifespan (as opposed to life expectancy, a very different thing) within reach."

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