To my eyes, Chronosphere is chiefly important as an insider's personal view of the 40-year history of modern cryonics movements. For decades, people have been working on the indefinite low temperature storage of the deceased, aiming to preserve the fine structure of the brain that encodes the mind's data. There is, to my eyes, still far from enough of a recounting of that history, the lessons learned, and efforts made - the more memoirs and personal accounts presented online the better. So here are pointers to a couple of recent Chronosphere posts on what went on, back in the day, when cryonics was a younger initiative, both of which are liberally scattered with photographs:

In Camera Historia: Cryonics Institute Facility, 1978

On 21 March, 1978 the Cryonics Institute (CI) acquired their first facility, a storefront building in the Detroit Metro area. The CI building was the first wholly owned (cash purchase) patient storage facility in the history of cryonics, and remains one of only two in the world today. ... As was the case with all cryonics organizations' initial facilities, the CI facility was small and cramped. It also lacked the ceiling height necessary for upright (open at the top) cryostats and this limitation was an additional impetus for CI to develop the fiberglass-epoxy resin type of cryostat (using perlite and low vacuum insulation) that they currently use to store their patients.

The Armories of the Latter Day Laputas, Part 7

The Alcor Life Extension Foundation, Inc. (Alcor) and its brother for-profit organization, Manrise Corporation (Manrise), were founded in 1972 by Fred and Linda Chamberlain ... The Chamberlains had previously been members of the Cryonics Society of California (CSC) and both had served as officers of CSC. When they became suspicious about the integrity of CSC's financial and cryogenic patient care operations and were unable to obtain answers to their questions, they left CSC and founded Alcor/Manrise. As was the model at the time, Alcor was the 501c3 non-profit organization tasked with accepting cryonics patients under the Uniform Anatomical Gift Act (UAGA) and acting as their custodian and advocate until such time as reanimation might become possible.

If this were a better world then cryonics or a similar industry based on plastination would be large and well known, and a majority of people would be spared the oblivion of the grave. We don't live in that world, evidently, and is a sad statement on vision, priorities, and human nature that cryonics remains a small industry.

From TechNewsWorld: "In America, a large part of funding for regenerative medicine comes from the Department of Defense, whose goal is to repair soldiers who come home wounded. That is an effort everyone recognizes as important. Yet, when it comes to repairing older people whose hearts and lungs are failing, society seems at peace accepting their demise because that is all humanity has ever known - a state of mind that some call the 'pro-death trance.' ... A Swedish hospital recently announced that a cancer patient was saved after doctors grew him a new windpipe in the lab using a synthetic structure and the man's own stem cells. That might have sounded like science fiction just a few years ago, but today it is landmark news. Regenerative medicine has the ability to usher in radically longer and healthier lives, yet few are considering the implications. The ability to grow new replacement parts for humans when original organs break down is a game-changer when it comes to extending human 'health spans' - the amount of time one is alive and healthy. A handful of human subjects have already benefited from innovations in this area and dozens of organs have been successfully grown in the lab, including a rat heart. ... The coming changes will be enormous - but on the whole, positive. Why then, is there no sustained dialog about how to get to that point sooner? ... Humans now have the opportunity to live much longer and healthier lives - for the greater benefit of all. It is time to break free from the pro-death trance and work toward speeding the revolution."

Link: http://www.technewsworld.com/story/America-Its-Time-to-Snap-Out-of-the-Pro-Death-Trance-72907.html

Does blood type in any way affect longevity? A resounding "maybe" from what little work exists on the topic, which suggests that if there is any effect then it is small in comparison to other factors. But we'll never know unless the research community looks into the matter, and so here is another batch of evidence to add to the pile: "Centenarians are the best example of extreme human longevity, and they represent a selected population in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. The study of the long-lived individual genetic profile has the purpose to possibly identify the genes and the allelic variations influencing extended life expectancy, hence considering them as biomarkers of age-related diseases onset and development. The present study shows no significant differences between allelic variations of ABO blood groups among a group of centenarians from Western Sicily."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21766224

Over at h+ Magazine you'll find a question and answer session with Aubrey de Grey that covers some old ground and some new ground. The SENS Foundation, which de Grey cofounded, is presently deploying a modest million-dollar yearly budget to work on the biotechnologies needed to repair the cellular and molecular damage that causes aging. A great deal of that budget presently goes towards the first of the Foundation's programs, an effort focused on using bacterial enzymes to break down harmful waste chemicals that build up in our cells and contribute to a range of age-related diseases and degenerations.

I should mention that SENS Foundation funding is due entirely to philanthropic donations - including those of a few high net worth individuals - and I know that many of the readers here are long-standing supporters dating back to the years when the SENS Foundation's work was a program of the Methuselah Foundation. I find it very gratifying to see that so much has been made of the early efforts, when it was a matter of a few dollars given at time. I would hope that the rest of you feel the same way.

The SENS Foundation will also be hosting the forthcoming SENS5 conference in Cambridge at the end of August - there's a lot going on at the moment. But back to the h+ Magazine piece:

H+: SENS describes a whole battery of medical treatments that could theoretically defeat the aging process. These treatments range from relatively simple ones like injecting people with enzymes that can break down tough wastes inside of cells, to highly advanced ones like genetically altering trillions of somatic cells in full grown adults. Considering the differential technical challenges, what SENS therapies will most likely become available first, and which will be developed last?

AdG: Some of them are already pretty close: probably the closest is in fact not the enzyme therapy you mention, but the use of vaccines to eliminate extracellular aggregates (especially amyloid). But when we consider the others, actually I wouldn't like to make the call, because the hardest ones are the ones that the SENS Foundation and I are prioritizing in terms of the early research. In other words, we're hoping that they will start to catch up with the easier ones. I suspect that the challenge of genetically modifying a high proportion of cells by somatic gene therapy will have been largely solved before we complete the development of all the genes that we want to introduce.

...

H+: Are you worried that a single company or government might obtain the secrets to longevity first and then use its monopoly on the science to hold the human race hostage forever (or even for just a long period of time)?

AdG: There's no chance whatever of this scenario, because the defeat of aging will depend on the simultaneous application of a lot of different interventions, all of which will first have been developed in the laboratory rather than in humans.

There's a lot more in that vein, so read the whole thing. The point on gene therapy in the quote above is an interesting and important one. A great many very promising demonstrations in the laboratory depend upon gene therapy in one form or another - take the method of largely preventing atherosclerosis I pointed out earlier today for example. If we want to see these lines of research become more than simply interesting technology demonstrations then selective, tissue-specific gene therapy for humans must become routine and safe.

A translated interview with SENS Foundation co-founder Aubrey de Grey: "I have identified seven types of damage [that cause aging]. In five cases we can repair the damage in my opinion, by replacing irreversibly damaged cells by stem cells, or when garbage accumulates, we will remove [it]. In two cases, we need to engage in gene therapy, for example, through new DNA counteract mutations in the mitochondria. ... We should intervene as little as possible in the metabolic pathways themselves. This is too complicated, we do not know enough yet about it. I prefer the regenerative approach, the repair and maintenance. It is [sufficient] to repair the damage after it occurred. In this way, we do not [need to] understand all the molecular details and how they come about. But we have to intervene before the problems get out of control. ... A simple example is the stiffening of the extracellular matrix - this is the fibrous scaffold between cells. The stiffening occurs because certain molecules network with each other. There is a principal [agent], a molecule called [glucosepane], which has the largest share of the networking and reinforcement. We must find a way to break up about two-thirds of them again. If we break these reinforcements, it would eliminate about half of the damage. ... I think the probability is about 50 percent, that all of these therapies in 25 years actually show the desired results. The average life span might then be [increased by] about 30 years."

Link: http://translate.google.com/translate?u=http://www.heise.de/tr/artikel/Muell-entfernen-und-Zellen-erneuern-1230091.html

Cryonics, as I'm sure you're all aware, has for decades been the best and only shot at a long life in the future for people who die before the advent of rejuvenation biotechnologies capable of reversing the damage of aging. That is a massive number of people, possibly including you and I unless we get our act together - and sadly, all too few will choose to be cryopreserved, even though they have the opportunity and the means. Cryonics is, in essence, a form of indefinite low temperature storage of the body and brain immediately following death. It is carried out with the reasonable expectation, based on present scientific knowledge, that it preserves the fine structure of the brain that stores the information of the mind - you might not be running, but all your data is backed up.

We can envisage the technologies needed to restore a preserved person to active life once again, and none of it is prohibited by the laws of physics. It most likely require a far greater understanding of the structure human brain, the ability to build a new body from scratch, the use of a molecular manufacturing technology base and swarms of nanoscale medical robots, capable of manipulating and repairing cellular machinery - and the computational power to support sophisticated use of these medical technologies. But all of these are foreseeable, and presently being worked on by a range of research groups. It isn't pie in the sky to expect there to be a chance of resuscitation for cryopreserved individuals. Their lives are on hold, but not gone - you are only irrevocably gone if you choose the grave.

But how does a cryopreservation work in practice? How does one go from the last weeks of life to being safely stored in liquid nitrogen, awaiting the future? As I've noted in the past, it takes a fair amount of organization to do well, and the regulatory environment surround end of life choices doesn't make a good cryopreservation any easier - you are not allowed to choose when to do it, and in most jurisdictions no-one is allowed to help you plan your death to be at the time of your choosing either. If you want to learn more about how a cryopreservation tends to unfold, then you should note that cryonics provider Alcor publishes case summaries on a regular basis, as patients are preserved. You'll find some referenced back in the Fight Aging! archives, and here are a couple of recent case summaries:

Case Summaries: A-1408 and A-2357:

This past quarter, Alcor cryopreserved two of its members. The first member, A-1408, lived just north of the Tampa, FL area. Alcor team members initiated a standby at the hospital for three days during the time the individual was listed as critical and medical providers anticipated that he might stop breathing. The member stabilized and Alcor ended the standby while continuing to monitor the patient's condition remotely. When his medical condition deteriorated again, Alcor was on the verge of initiating a standby for another member and therefore decided to request Suspended Animation to provide the standby this time.

On the afternoon of the fourth day of the standby (May 26, 2011), the member was pronounced, stabilized and cooled on-site, followed by a field washout. The transport commenced the next morning by commercial airlines and the patient was brought to Alcor with the surgical team at the ready. After the neuro cryopreservation ensued, member A-1408 became Alcor's 105th patient.

Case Report for A-1614 (PDF)

Wesley Du Charme authored a book: Becoming Immortal: Nanotechnology, You and the Demise of Death in 1995, which discussed the opportunity for virtual immortality through combining nanotechnology and cryonics. He lived life fully while always looking to the future; he joined Alcor in hopes of living in the far future.

....

The tests showed that Wesley now had pancreatic cancer with metastases to the liver and duodenum. At this point, the oncologist said that his condition was terminal and nonoperable, and Wesley would not respond to chemo or radiation treatments. When asked how long Wesley had to live, he responded with "...longer than three days, but less than six months."

Given Wesley's greatly weakened condition, the family desired to have him admitted to hospice care in Scottsdale, Arizona, close to Alcor. As Wesley was currently hospitalized, his physician who was supportive of the cryopreservation directives, prescribed TPN (Total Parenteral Nutrition) as a way to increase Wesley's strength and stamina to endure the trip to Arizona. Alcor personnel helped facilitate communication between the hospice facility and the family to finalize the admittance process.

You should read the whole PDF document, and be appreciative of the folk who were thoughtful enough to allow a detailed account of the arrangement of Du Charme's cryopreservation to be published. The end of a life and the terminal breakdown of a body's necessary systems are never pretty, and most people prefer to sweep all of that behind the curtain - and the same goes for the hundred small organizational details that go into managing death and cryopreservation. But if they aren't published, we don't learn.

Via EurekAlert!, news of a promising study in rabbits: "A one-dose method for delivering gene therapy into an arterial wall effectively protects the artery from developing atherosclerosis despite ongoing high blood cholesterol. ... As applied in our study, the introduced genes can produce proteins that counteract the fundamental processes that drive atherosclerosis, including preventing lipid accumulation inside the artery wall and decreasing recruitment of inflammatory cells. We found both of these effects. ... Gene transfer would move the production of the therapeutic 'drug' (in this case a therapeutic gene) directly to the site of atherosclerosis development: the blood vessel wall. The approach maximizes delivery of the drug to the artery wall and minimizes side effects in the rest of the body. ... The deployed gene produces a protein that is likely responsible for the beneficial effects of high-density lipoprotein, or HDL, commonly known as good cholesterol. This substance is apolipoprotein A-1, or apoA-1. It pumps out harmful cholesterol from the scavenger-type cells that ingest fats and congregate in early atherosclerotic lesions. ApoA-1 appears to remove cholesterol from the lesions and is capable of transporting it to the liver, where it can be excreted from the body. Lack of a suitable vector to transfer apoA-1-manufacturing genes into the cells lining the arterial wall has hampered the progress of this approach. Normally apoA-1 is produced by cells in the liver, stomach and intestine and enters the artery wall only after circulating through the blood. [The] researchers successfully used a helper-dependent adenovirus (HDAd) as the vehicle to transfer a genomic clone of rabbit apo-A1 into the carotid artery. This large blood vessel sends oxygenated blood to the brain. After the vector was infused into the artery, the gene was taken up almost exclusively by the cells in the thin layer that lines the carotid's inner surface and is in contact with circulating blood."

Link: http://www.eurekalert.org/pub_releases/2011-07/uow-gtd071911.php

An open access paper: "Nearly 50 years ago geneticist James Neel famously proposed that 'thrifty genes' were important contributors to the rising prevalence of diabetes. Such genes promote efficient use and conservation of food energy, he theorized, and thus were favored by natural selection to help our ancient ancestors cope with famines. Now widespread in various populations, they predispose to obesity and diabetes, abetting a tendency to prepare for famines that never come. ... Here I propose an extension of this reproduction-centered version of Neel's theory that bears on aging. One of my key premises is that many windows of opportunity for reproductive booms occurred during the Holocene as agricultural innovations spread, periodically increasing food availability between times of nutritional stress. The periods of plenty selected for genotypes capable of rapidly ramping up fecundity as food intake increased. ... I believe the boom times' selection of genotypes prone to nutrition-cued accelerated development is having an especially problematic effect today because of widespread childhood overnutrition. Accelerated development, which enhanced reproductive success in the past, now has a pro-aging effect with rapidly growing costs. Indeed, when viewed through the lens of the antagonistic pleiotropy theory of aging, this effect seems anything but thrifty: It predisposes toward what might be called the spendthrift phenotype, characterized by chronic activation of pro-growth pathways - notably those involving mTOR, insulin, and insulin-like growth factor-1 - that support rapid development and sexual maturation but that also underlie later senescence. The modern fallout encompasses a much broader array of age-associated ills than the diabetes that prompted Neel's original hypothesis. Indeed, the spendthrift phenotype may well increase the age-associated risks of most if not all diseases of aging, like the ruinous adult legacy of flush, fast-living youth."

Link: http://www.impactaging.com/papers/v3/n2/full/100286.html

Some species do not age in any easily detected way - lobsters, for example. Others are just far more resilient to the passage of years than we humans, living longer or losing little of their vitality over the course of their lives. What can be learned from a study of their biochemistry? "The first photo is from 1973, when a dark-haired and spry Nisbet was banding chicks of the small sea bird off the rocky Cape Cod coast. The second photo was taken 33 years later and shows a grizzled, silver-haired Nisbet holding a 29 year old tern, one of the oldest on record. Nisbet's body shows common signs of wear and tear - gray hair, wrinkles, achy joints. The tern, however, shows none of these outward signs, despite being the equivalent of a human centenarian. ... Terns don't even demonstrate diminished physical abilities as they age. They aren't the only animals that have combined a long lifespan with minimal signs of aging; other seabirds, alligators, crocodiles, and some tortoises also seem to sip from the Fountain of Youth. Although medical advances have extended the human lifespan, these same advances haven't been able to prevent the inimical onslaught of old age. Scientists hope that by studying the secrets of ageless critters, humans will one day be able to pause the hands of time. ... The main difference between humans and organisms like common terns is how growing older affects the risk of dying. ... In some animals, like freshwater hydras, risk of death remains pretty constant during life. For other animals, like the tern, the risk of death actually decreases with age. It seems almost counter-intuitive: an older tern is less likely to die than a younger one. 'My 29-year-old tern was still breeding,' Nisbet said. The oldest terns produced the healthiest offspring and were actually more likely to survive the year than younger terns."

Link: http://www.physorg.com/news/2011-03-ageless-animals-scientists-clues-aging.html

Autophagy is important in determining life span, probably because of its role in clearing out damaged mitochondria (a process known as mitophagy) before they can cause other forms of harm. Here is evidence for that view in the form of a link between Parkinson's disease and autophagy: "Mutations that cause Parkinson's disease prevent cells from destroying defective mitochondria ... Defects in the ubiquitin ligase Parkin are linked to early-onset cases of this neurodegenerative disorder. The wild-type protein promotes the removal of impaired mitochondria by a specialized version of the autophagy pathway called mitophagy, delivering mitochondria to the lysosomes for degradation. Mitochondria are often dysfunctional in Parkinson's disease ... cells expressing mutant forms of Parkin failed to clear their mitochondria after the organelles were damaged. Different mutations blocked mitophagy at distinct steps: mitochondria accumulated in the perinuclear region of cells expressing Parkin lacking its ubiquitin ligase activity, for example. The researchers found that ubiquitination of defective mitochondria by Parkin normally recruits the autophagy proteins HDAC6 and p62 to clear these mitochondrial aggregates. ... The clearance of defective mitochondria is therefore similar to the removal of damaged proteins, another autophagic process that goes wrong in Parkinson's disease resulting in the accumulation of toxic protein aggregates. Both pathways rely on microtubules, HDAC6, and p62, [providing] a common link between the two main features of the neurodegenerative disorder."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/rup-mtc050610.php

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

These researchers argue that embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are most likely the same in any aspect that matters: "the pluripotency of ES cells fueled excitement over their use in regenerative medicine. While ethical hurdles associated with the clinical application of human ES cells appeared to have been overcome with the development of methods to create iPS cells, some recent research has suggested that ES and iPS cells have substantial differences in which sets of genes they express. These findings [argue] to the contrary, rekindling hopes that, under the proper circumstances, iPS cells may indeed hold the clinical promise ascribed to them earlier. ... iPS cells are made by introducing three key genes into adult cells. These reprogramming factors push the cells from a mature state to a more flexible embryonic stem cell-like state. Like ES cells, iPS cells can then, in theory, be coaxed to mature into almost any type of cell in the body. Unlike ES cells, iPS cells taken from a patient are not likely to be rejected by that patient's immune system. This difference overcomes a major hurdle in regenerative medicine. ... At this stage, we can't yet prove that they are absolutely identical, but the available technology doesn't reveal differences. ... Some earlier studies have indicated that iPS and ES cells are dissimilar enough to be classified as different cell types. [The researchers] concluded that the differences noted in other studies were not consistent between different laboratories and thus were not likely to be a result of fundamental differences between the cell types."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-08/wifb-hes080510.php

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

In a nutshell: "Adipose tissue accounts for approximately 20% (lean) to [more than] 50% (in extreme obesity) of body mass and is biologically active through its secretion of numerous peptides and release and storage of nutrients such as free fatty acids. Studies in rodents and humans have revealed that body fat distribution, including visceral fat (VF), subcutaneous (SC) fat and ectopic fat are critical for determining the risk posed by obesity. Specific depletion or expansion of the VF depot using genetic or surgical strategies in animal models has proven to have direct effects on metabolic characteristics and disease risk. In humans, there is compelling evidence that abdominal obesity most strongly predicts mortality risk, while in rats, surgical removal of VF improves mean and maximum life span. There is also growing evidence that fat deposition in ectopic depots such as skeletal muscle and liver can cause lipotoxicity and impair insulin action. Conversely, expansion of SC adipose tissue may confer protection from metabolic derangements by serving as a 'metabolic sink' to limit both systemic lipids and the accrual of visceral and ectopic fat. Treatments targeting the prevention of fat accrual in these harmful depots should be considered as a primary target for improving human health span and longevity."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20703052

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

An interesting experiment, especially when compared with work on brain aging that focuses on levels of cell proliferation: "During the past decade, it has become increasingly clear that consistent changes in the levels of expression of a small cohort of genes accompany the aging of mammalian tissues. In many cases, these changes have been shown to generate features that are characteristic of the senescent phenotype. Previously, a small pilot study indicated that some of these changes might be reversed in rat liver, if the liver cells became malignant and were proliferating. The present study has tested the hypothesis that inducing proliferation in old rat liver can reset the levels of expression of these age-related genes to that observed in young tissue. A microarray approach was used to identify genes that exhibited the greatest changes in their expression during aging. The levels of expression of these markers were then examined in transcriptomes of both proliferating hepatomas from old animals and old rat liver lobes that had regenerated after partial hepatectomy but were again quiescent. We have found evidence that over 20% of the aging-related genes had their levels of expression reset to young levels by stimulating proliferation, even in cells that had undergone a limited number of cell cycles and then become quiescent again. Moreover, our network analysis [may] provide insights into mechanisms involved in longevity and regeneration that are distinct from cancer."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22477361

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

I view the world of aging and longevity science as divided into three broad classes of research and researchers - something that will already be apparent to regular readers, but which I don't recall having outlined explicitly. This crude model of the research community informs the ways in which I read research and evaluate the state of progress towards meaningful goals: both extension of healthy human life, and - more importantly - forms of medicine capable of repair and reversal of aging.

Class 1: Investigating Aging

By far the largest component of the aging science community is made up of researchers who are not working on ways to alter or repair the aging process. They investigate only, and thus the majority of funds devoted to the science of aging still go towards studies that aim to make no difference to the world beyond gathering data. This group include most of those who run demographic studies of human longevity, for example.

Aging research is unusual in the medically-relevant life sciences by virtue of this preponderance of "look but don't touch." Up until comparatively recently it was extremely hard to find funding or respect for work that aimed to do more than gather data on aging; the scientific community worked to exclude those who had such goals in mind, and funding sources closed their doors to anyone known to harbor heretical thoughts about extending human life through biotechnology.

Class 2: Working to Slow Aging

The larger minority class in aging research is made up of researchers and funding institutions who are working towards ways to slow aging, or working on related areas that will be used in constructing therapies to slow aging. The typical approach here is to reverse engineering the genetic and other low-level biochemical roots of known differences in longevity (such as the effects of calorie restriction, or the differences in life span between similar species), and then try to reproduce some of those differences using drugs, gene therapies, and other similar means. The view of these researchers is largely that we are a long way from any practical results, and those results will only offer incremental gains - a viewpoint I agree with.

Nonetheless, this class is where much of the energy and vigor is in funding and growth for aging research. This may be because this general research strategy is easily understood by traditional sources of funding, and is only an incremental alteration to previous forms of old-school drug development work.

The sea change in the aging research community over the past decade or so has largely manifested as a transformation of researchers from the bulk of class 1 into up and coming enthusiasts of class 2. As it became respectable to talk about doing something about aging - thanks to the hard work of a comparatively small number of advocates and visionary scientists - there has been a steady shifting of research priorities. The investigators still outnumber research groups working on ways to alter the course of aging, but the trend is clearly towards a field that develops clinical applications in medicine rather than only informing the medical profession of what to expect in their patients.

Class 3: Working to Reverse Aging

The smallest and most important cohort of researchers are those who are working on ways to repair, reverse, or work around the root causes of aging - the SENS Foundation research network being the archetype, though not the only set of researchers and laboratories involved in this work. This class are the most important because their approach is the only viable path we can see that has a good chance of producing rejuvenation biotechnology capable of greatly extending healthy life in the elderly - through restoring youthful function and vigor. This is the smallest cohort because we do not live in a particularly rational world.

I have discussed in the past why it is that repair based strategies are so very much better than approaches based on slowing down aging. The short of it is that aging is a matter of damage: slowing down the pace of damage will do little for people who are already old, while repairing damage will be beneficial to everyone. You can only achieve rejuvenation through actual repair, not by slowing down the rust. Given that the cost of producing therapies from the two very different strategic approaches to medicine for aging will likely be in the same ballpark, we should evidently aim for the better outcome.

There is also the matter of time - it will be decades before either side of the house has a mature base of therapies in place, and by the time those therapies are available those of use with the greatest vested interest in using them will be old. So only the strategy of aiming for rejuvenation offers the chance of an outcome that grants additional decades at the end of the day - enough time to push past actuarial escape velocity and thus be able to wait out the advent of even better therapies.

But cogent arguments aside, the greatest growth in aging research is still amongst class 2, those working on the slow road to a poor end result. Now that the research community is essentially persuaded to the view that work on aging is good, interesting, and plausible, the next - and equally important - goal of advocacy is to persuade a great many more researchers to work on the SENS vision for rejuvenation biotechnology or equivalent scientific programs.

Many, many lives depend on it.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

An article on recent sirtuin research - while extended longevity is demonstrated, I don't think it changes the big picture on sirtuins all that much: "Mammals, including humans, have seven types of sirtuins, called SIRT1 to SIRT7. Scientists aren't sure what these proteins do, although there is some evidence suggesting that they might help prevent chronic diseases such as cancer and cardiovascular disease. For example, resveratrol, the nutrient found in grape skins (and red wine), has been shown to have a positive effect on heart health, and it may work by activating the SIRT1 gene to make more SIRT1 protein. The Israeli researchers, led by Yariv Kanfi, focused on SIRT6. The team's previous work revealed that mice genetically bred to have lots of SIRT6 could get fat on rich diets yet show no signs of heart disease, fatty liver disease and other diseases associated with obesity. Previous research by other groups showed that mice genetically bred to have little SIRT6 don't live very long. And, conversely, rats living longer on a calorie-restricted diet have increased levels of SIRT6 in their blood. So, this time the Israeli team simply decided to let the SIRT6 mice live a natural life. These male mice lived longer, about 16 percent longer on average, than regular mice kept in the same conditions. The female mice with the SIRT6 gene enhancement didn't live longer than regular mice. The researchers speculate that, considering how male mice have a higher rate of cancers compared with the females, the SIRT6 could be acting as a tumor suppressor and thus have a larger effect on male life span than female life span."

Link: http://news.yahoo.com/anti-aging-protein-extends-life-span-mice-maybe-180802189.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

At the end of a post on the science of aging, filmmaker Robert Kane Pappas says the following on the goal of greatly extending human life:

Actual age reversal was something - that, when I first heard of it 5 years ago - I put in the category of time travel and ghosts. [But] after 5 years of interviewing the researchers and poking around labs with my camera, it is not a question of if but when. The general population has little idea of what is about to befall them.

Which is both true and a problem. From an advocate's point of view, I'd say that unless a much larger portion of the public gains an understanding of longevity, the level of support will not rise far enough to generate the large sums of money needed for meaningful progress within the next 20 to 30 years. Outside of stem cell medicine and cancer research, the necessary research programs to build rejuvenation biotechnology are somewhere between fringe, anemic, and non-existent, relatively speaking - and it's only the dedicated efforts of groups like the Methuselah Foundation and SENS Foundation that have boosted these research projects to be more than non-existent. The present few million dollars a year is a lot in one sense, but a drop in the bucket in comparison to the the hundred of millions that are necessary for real progress.

Given that, I feel I can say that if the first fruits of longevity science come as a surprise to the world at large, to the average fellow in the street, then those advances will likely be faltering and far less imposing than might have been possible. On the large scale progress in science and medical technology is a numbers game: the more public support there is, the easier it becomes to raise funding, the more researchers become interested in working in the field, and the more entrepreneurs step forward ... and the wheel turns faster as a result. To gain that greater public support requires persuasion, communication, and education - informal and otherwise - are thus it is these line items that are the roots of progress when looking at breadth of society and a length of decades.

And still, today, the public is indeed largely oblivious to longevity science - not at all aware of the possibility that biotechnologies already envisaged in some detail could be rejuvenating the old 20 to 30 years from now. That future is uncertain: it depends on many more people grasping the idea and the potential, and doing their part to help provide the research community with a full head of steam and major funding.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

One of the underlying mechanisms by which the advanced glycation endproducts (AGEs) that build up with age cause harm is through hammering on the receptor for AGEs, or RAGE. Some Alzheimer's researchers are looking into targeting RAGE in order to remove the contribution of AGEs to that condition, and it is possible that the results of their work may have more general application to AGEs in aging - though the best possible strategy would be to remove the AGEs rather than work around them: "Researchers have taken another crack at a promising approach to stopping Alzheimer's disease that encountered a major hurdle last year. ... scientists have developed a compound that targets a molecular actor known as RAGE, which plays a central role in mucking up the brain tissue of people with the disease. Scientists [synthesized] a compound that stops RAGE in mice - reversing amyloid deposits, restoring healthy blood flow in the brain, squelching inflammation, and making old, sick mice smarter. But the scientists caution that the work has a long way to go before it's considered as a possible treatment in people. ... A phase 2 study in 399 people of another compound designed to stop RAGE - which stands for Receptor for Advanced Glycation Endproducts - was halted prematurely in November when scientists had questions about the compound's safety at high doses, and after early results indicated that the compound was not helping patients with Alzheimer's disease. ... The benefits of blocking RAGE are even greater than has been realized. RAGE is central to many mechanisms that wreak havoc in the brains of people with Alzheimer's disease. It turns out that when you inhibit RAGE, you block molecules central to creating inflammation in the brain, and that is a major problem with Alzheimer's disease."

Link: http://www.urmc.rochester.edu/news/story/index.cfm?id=3440

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

If you go through the first half of your life basically healthy, there are actually only a few important differences between your situation and that of your ancestors a century or two ago when it comes to health and medical technology. For all that we live in the opening years of an era of advanced biotechnology, and in an age of far greater wealth, a healthy person benefits only through (a) the reduced burden of infectious disease, and (b) through the insulating effects of wealth against malnutrition, exposure, and other environmental misfortunes. These two points are enough to explain much of the steady rise in life expectancy that occurs with growing wealth and advancing medical technology over the past centuries.

What is the point of mentioning this? It is to remind us that we are not bathed in the golden aura of biological science, and the many ways to extend the healthy lives of mice demonstrated in the laboratory over the past decade have not yet translated into any medical technology we can use. As a healthy person in the US or Europe, the trajectory of your life under present day medicine isn't in fact terribly different from that of a privileged and healthy individual in the late 1800s. The only differences lie in your burden of infectious disease and the ability for even today's poor to enjoy a degree of protection from life's slings and arrows that was once only affordable to the wealthy. The trajectory of your life will only change meaningfully when prospective technologies for reversing the damage of aging are developed and become available in the clinic. Until then, you are only incrementally better off.

From the perspective of the life sciences and medical technology, these are amazing years to be alive, as I'm sure you've already noticed if you're a regular reader at Fight Aging! Yet that means exactly nothing for us until laboratory work is built into clinical applications. Detailed descriptions of technologies that can reverse aging give us hope, but nothing other than hope until the job of turning descriptions into real therapies is complete.

There are all too many people in the world who are happy to partake in the growing hope of engineered longevity and human rejuvenation, but who then sit back and do nothing to help bring about that desired future. And so the world works as it has always done: if everyone drinks hope and air, then hope and air is all that will come into being. Medical technologies do not develop themselves. They only arise in an environment of support, aggressive fundraising, and widespread agitation for their creation - environments in which a lot of people are materially contributing, in other words.

So don't feel as though you are made shielded or special by the fact that biotechnology is in the zeitgeist: you aren't, and you won't be until much more work is accomplished. Give some thought to helping out: after all, your life is as much on the line as everyone else's.

Here is a repetition of the sort of research from the last century that initially drew interest to calorie restriction, in which researchers are trying to pin down the point at which beneficial calorie restriction becomes harmful malnutrition: "It has been firmly established that the longevity of 20- to 60 %-calorie-restricted rodents, with malnutrition (essential nutrients deficiency) being avoided, is increased when compared to ad libitum fed rodents. However, the effects on life span of severe dietary restriction (i. e. malnutrition), with limited weight loss, remained unknown. The purpose of this 4-year study was to investigate the effects on longevity of a severe form of dietary restriction, with limited and controlled weight loss. To this end, a group of male Long-Evans rats severely dietary restricted (SDR group), with a weight loss throughout the experiment <= 25 % of their weight before the onset of the experiment at 9 weeks of age, was compared to a control group of rats 30- to 40 %-calorie-restricted (C group). Our results show that a severe dietary restriction, excessive weight loss being prevented, paradoxically increased rat longevity by nearly 50 %. The life span increase observed in our SDR rats is in accordance with some other studies investigating the effects on longevity of partial essential nutrients deficiencies (tryptophan, methionine, and fat, for example)."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21792819

The Technology Review looks at the work of researchers attempting to restore youthful function in brain cells associated with memory: "By delivering a certain chemical to the brain, researchers could make neurons in old monkeys behave like those in young monkeys. Clinical trials of a generic drug that mimics this effect are already underway. The findings support the idea that some of the brain changes that occur with aging are very specific - rather than being caused by a general decay throughout the brain - and can potentially be prevented. [Researchers] recorded electrical activity from neurons in a part of the brain called the prefrontal cortex, a region especially vulnerable to aging in both humans and [other] primates. It is vital for our most high-level cognitive functions, such as working memory and the ability to multitask and inhibit distractions. ... neural circuits in this region are organized to create a sustained level of activity that is crucial for working memory. ... By analyzing activity recorded from young, middle-aged, and old monkeys, the researchers found that the firing rate of the neurons in this area declines with age. They found that other neurons, such as those that respond to cues in the environment, still fired normally even as the monkeys aged. ... The researchers were able to rein in the problem by treating the cells with a drug that blocks the potassium channels. After treatment, brain cells in old monkeys fired more rapidly - just like those in their younger counterparts. The researchers already knew that giving monkeys this drug systemically, rather than delivering it directly into the brain, could reverse age-related deficits in working memory. A clinical trial of the compound, a generic drug called guanfacine, originally used to treat hypertension, is underway."

Link: http://www.technologyreview.com/biomedicine/38158/