Fight Aging!

Maria Konovalenko is a molecular biophysicist and program coordinator for the Science for Life Extension Foundation, an organization that might be seen as the Russian equivalent of the SENS Foundation or Methuselah Foundation. There is the same dedication to extending healthy human life span, the same strong connections to the scientific community, and similar outreach programs. If you haven't already done so, you should take a look at the Foundation's website via Google Translate.

In any case, Konovalenko came to my attention as an advocate for engineered longevity a little while back via a well-done video presentation. Now I see that she has a blog up and running; a couple of recent posts caught my eye:

Bubonic plague

Almost every time when the conversation drifts to fighting aging the majority of people loose the common sense. Here’s how a typical dialog about aging looks like, but the word "aging" is substituted with "bubonic plague":

Bubonic plague fighter: There’s a huge problem in our city - we've got an epidemy of bobunic plague. If we do nothing, everybody will die in the throws of bubonic plague.

Inhabitant of the city: Let's take a look at the problem from another point of view: if nobody dies from bubonic plague, our city will be overpopulated.

...

Bubonic plague fighter: Then why do we try to conquer other diseases, but not the bubonic plague? If there were a vaccine, people would not refuse it! People have always tried to do what's best for them. Now that's natural.

Inhabitant of the city: But bubonic plague can not be defined as a disease, because nobody is trying to overcome it and there's no cure for it. This is what nature gave us. It can not be cured.

15 mistakes of an investor who funds research on life extension

Despite everything that I am going to write further the biggest mistake of an investor is to think that someone else is going to fund the search for interventions into human aging, growing and creating artificial organs. Despite quite a large number of news on this topic there are no breakthroughs yet, and that's mostly because the lack of money and good management. I'd like to note that capitalization of a dead investor is equal to zero and it’s only research into life extension that can help him thrive on and on.

I find it interesting that there is so little investment in longevity engineering, all things considered. When you are good at turning time into money, the most valuable long term investment you could make is into developing ways to turn money into time.

There is a lot that can be said on this topic: for example, we might blame stoic cultural inertia, that state in which people are unwilling to write off the great effort it took to come to terms with their own future demise. Or perhaps we point the finger at the vile "anti-aging" marketplace, whose leaders direct vast sums in advertising to convince people that when it comes to extending healthy, youthful life, the only things out there are fripperies, cosmetics, lies, and scammers. Maybe we throw up our hands and choose to believe that, given the way in which human nature discounts future value, most people for most of their lives are actually not all that interested in living longer. Then there's Aubrey de Grey's triangular logjam analogy for the way in which vested interests and human behavior have built an edifice that resist progress.

I could go on. But none of these line items are unique to the intersection of aging, advancing biotechnology, and human longevity. Every great shift in culture and technological prowess was at some point an uphill struggle. We humans just don't like change, and no matter that a given change is good - the mainstream will still be enthusiastically against it before they are reluctantly for it.

Advocacy and progress is a process, and in the case of engineering greater human longevity it is a process we are well in the midst of: changing views, advancing science, the great and confusing conversation about aging and longevity that spans all media and all interested parties. To be in the middle as matters unfold makes it hard to see the big picture, but we can be assured that a great deal of work has taken place, a great deal of work is to come, and medical technology is advancing. We can do little wrong by continuing to work at make the future arrive more rapidly.

The results of this study make for an interesting comparison with research that demonstrates lack of blood vessel dilation in muscles to be a root cause of age-related loss of muscle mass, or sarcopenia: researchers "have determined that moderately and temporarily restricting the flow of blood through muscles - a practice adopted by bodybuilders who noticed that it made light weights feel heavier - can be combined with low-level resistance exercise training to produce muscle-mass increases in older men. ... investigators studied changes in the thigh muscles of seven older men (average age 70) when they performed four minutes of low-resistance leg extension exercises both with and without inflatable cuffs that reduced blood flow out of the muscles. Muscle protein synthesis was measured in each of the men by monitoring changes in a chemical tracer infused into the bloodstream. In addition, a series of biopsies yielded muscle samples that were analyzed to track alterations in biochemical pathways critical to muscle growth. ... We saw that when we put the cuffs on, they responded similarly to young people doing traditional high-intensity resistance exercise."

Link: http://www.sciencedaily.com/releases/2010/05/100514151926.htm

From Life Extension Magazine: "the name 'regenerative medicine' came from Bill Haseltine, then of Human Genome Sciences, one of the early leaders in genomics and DNA technology. Back in the 1990s, Bill learned that researchers in aging were making important progress on turning back the clock of aging in human cells through cloning, and then creating young cells that could potentially regenerate or repair all the tissues of the aged human body. And so, upon hearing of that realistic prospect, he christened the field 'regenerative medicine' in the belief that it would one day become a major part of medical practice. So, based on its origins, I would define regenerative medicine as that collection of technologies that utilizes embryonic pluripotent stem cells and their derivatives to regenerate tissues in the body ravaged from disease, primarily degenerative disorders associated with aging. ... The problem with human biology is that the immortal reproductive cells that built you and me develop into differentiated cells within our bodies and as a result, lose the capacity to proliferate (divide) forever. So, the cells of the body are mortal, meaning they have a finite life span, and as our tissues age, or deteriorate from disease, our body has a finite capacity to regenerate and repair those tissues. As a result, we suffer progressive declines in function that lead to our death." There is more to aging than this, however.

Link: http://www.lef.org/magazine/mag2010/jun2010_Immortal-Stem-Cells-for-Anti-Aging-Therapies_01.htm

For a while now I have been using pmid.us as a shortener for what were at one point in time unwieldy PubMed URL formats. Those long-form PubMed URLs looked hideous in the Longevity Meme emails, were a pain to cut and paste, and generally cluttered the place up.

URL shortening services are, of course, now generally regarded as one step removed from the Devil: unreliable creatures who will fail at some unpredictable time and vanish utterly, leaving all your shortened URLs stranded and broken. Pmid.us unfortunately looks like having joined that party, as it has spent at least the better part of today being non-functional.

In lieu of an on-topic post today, this missive is to let you know I'll be trawling through the archives for pmid.us shortened URLs and replacing them with direct links to PubMed. The more modern PubMed URLs are much shorter and cleaner than they used to be, so I have no complaints on that score. This was in fact an easy enough task over at the Longevity Meme, and is already complete for that side of the house, but it will take me a while to sort out matters here at Fight Aging!.

So let this be a lesson for all - if you care about the long-term survival of your external links, steer clear of URL shortening services, no matter how convenient they may at first appear.

A lot of work has taken place in recent years on killing cancer cells by heating targeted nanoparticles. Here is an example of the present state of the art: "When irradiated with light, gold nanoparticles become hot quickly, hot enough to generate explosive microbubbles that will kill nearby cancer cells ... To boost this approach, researchers [have] developed a method for creating supramolecular assemblies of gold nanoparticles that function as highly efficient photothermal agents of a size designed to optimize their delivery to tumors. ... They first took gold nanoparticles, 2 nanometers in diameter, and decorated the nanoparticles' surface with adamantane. They then added two other constructs: cyclodextrin attached to a biocompatible polymer known as polyethylenimine, and adamantane linked to polyethylene glycol, another biocompatible polymer. When combined in various ratios, these three constructs quickly assemble into nanoparticles with well defined sizes ranging from 40 to 118 nanometers in diameter. Once the complexes were purified, the researchers then attached a tumor targeting molecule to the surface of the resulting supramolecular complexes. ... when irradiated with a laser beam, the temperature of the assemblies rapidly soared above 374 C, the temperature at which explosive microbubbles form."

Link: http://www.physorg.com/news194078270.html

Another step forward for tissue engineers: "scientists have created an eight-layer, early stage retina from human embryonic stem cells, the first step toward the development of transplant-ready retinas to treat eye disorders such as retinitis pigmentosa and macular degeneration that affect millions. ... The retina is the inside back layer of the eye that records the images a person sees and sends them via the optic nerve from the eye to the brain. Retinal diseases are particularly damaging to sight. More than 10 million Americans suffer from macular degeneration, the leading cause of blindness in people over 55. About 100,000 have retinitis pigmentosa, a progressive, genetic disorder that usually manifests in childhood. ... To mimic early stage retinal development, the researchers needed to build microscopic gradients for solutions in which to bathe the stem cells to initiate specific differentiation paths. ... creating transplantable retinas from stem cells could help millions of people, and we are well on the way. ... researchers are testing the early-stage retinas in animal models to learn how much they improve vision. Positive results would lead to human clinical trials."

Link: http://today.uci.edu/news/2010/05/nr_retina_100526.php

While wandering the internet today, my attention was drawn to a post on intermittent fasting (IF) and its relationship to calorie restriction (CR), a topic I've touched on in the past. The author examines a brace of research papers and concludes:

In summary, it looks like intermittent fasting extends lifespan in rats and mice only when it is accompanied by calorie restriction. It does not mean that the animals are also put on CR; rather, they just naturally end up eating less (unlike humans, who tend to be very flexible and good at compensating for calories). And, in the rare cases that the animals actually do eat twice as much the next day, their lifespans are not increased.

I'm not sure I agree with the comment on eating habits for either humans or mice. Anecdotally, it seems that you'd have to work pretty hard at eating to catch up on the calories missed by practicing alternate day fasting. It's not something that will just happen if you're eating ad libitum. But I'm not polling a large sample size with that question. Perhaps most people easily manage to eat two day's worth of calories in a day.

In the broader context of intermittent fasting, and as the author of the post above does point out, IF without CR in fact extends life span in nematode worms, a process which seems to happen through molecular mechanisms separate from those known to be associated with CR. In addition, IF without CR produces other health benefits in mice:

We report that when [mice] are maintained on an intermittent fasting (alternate-day fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.

Notice that those mice were capable of taking up the slack to consume twice as much on the eating days. It seems to vary from study to study as to whether animals will make up the difference.

The bottom line to all this remains much the same for now:

Both calorie restriction and intermittent fasting [can] produce significant health and longevity benefits in shorter-lived mammals such as mice, and at least significant health benefits in primates, including humans.

Far more research has been accomplished for calorie restriction, and uncertainty remains as to whether intermittent fasting is as good, definitely increases longevity, has a preferred method of practice, or whether it could even be harmful to long-term health if done incorrectly.

It seems plausible that calorie restriction and intermittent fasting produce their benefits in similar but different ways, based on research in lower animals, but I know of no research confirming this in mammals.

CNN Money is running a longer piece on calorie restriction mimetic research and the goal of slowing down aging to extend healthy life: "In early 1934, Depression-weary Americans were beginning to see tendrils of hope poking out of the bleak landscape. ... But one of the new year's most promising developments passed almost unnoticed. ... researcher Clive McCay was nearing the end of a four-year study that showed that rats' life spans were greatly extended when they were put on near-starvation diets. To many of his scientific peers, McCay's data made no sense at all. A glorious new chapter in nutrition science had been opened not long before by the discovery of dietary deficiencies behind scourges such as rickets, pellagra, and beriberi. In the wake of such progress, it seemed almost subversive to suggest that a bunch of rodent Oliver Twists, raised on such short rations that their growth was stunted, could live radically longer than well-fed ones. ... Over the next several decades, his discovery was all but forgotten outside of the back halls of science - a laboratory curiosity that didn't actually spark much curiosity. Most scientists were reluctant to risk wasting time probing an anomaly that seemed as baffling as aging itself. Calorie restriction (CR), as it's now called, eventually was shown to extend many species' life spans by a third or more. Now that anti-aging research is hot, it seems bizarre that CR spent decades on science's back shelf."

Link: http://money.cnn.com/2010/05/24/retirement/retire_rich_anti_aging.fortune/

A review paper: "The definition of sarcopenia continues to evolve, from an observational phenomenon to a differential diagnostic approach. Clinical relevance for sarcopenia is defined by a loss in lean muscle mass and impairment of functional status. A therapeutic approach to the loss of skeletal muscle mass and strength in older persons depends on correct classification. The term sarcopenia is reserved for age-related decline in muscle mass not attributable to the presence of proinflammatory cytokines. For persons with sarcopenia, the primary intervention should include resistance exercise. An improvement in muscle mass and strength has been demonstrated with resistance exercise, even in the very old. Targeting the hormonal changes with aging is an attractive intervention. However, testosterone replacement in elderly hypogonadal men has demonstrated only modest increases in muscle mass and strength. Administration of growth hormone in pharmacologic doses increases muscle mass but not muscle strength. Nutritional therapy is promising, but the effects in clinical trials have been small."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20497850

Researchers have uncovered what might be a new set of genes and protein mechanisms that influence healthy longevity: the epidermal growth factor or EGF pathway. The work was carried out in nematode worms, but the track record of such metabolic influences upon longevity carrying through into higher animals is pretty good so far.

The epidermal growth factor (EGF) peptide induces cellular proliferation through the EGF receptor ... Inhibitors of the EGF receptor are being pursued as potential cancer therapies and EGF may stimulate wound healing. Mutation of the EGF receptor has been associated with cancer in humans.

The best known of the metabolic mechanisms influencing longevity are those involved in insulin metabolism and calorie restriction - there may be some overlap between the two when all is said and done. The researchers here were in fact surprised to find that the results of their work did not point to insulin metabolism. Here's a reference to the paper:

Improving health of the rapidly growing aging population is a critical medical, social, and economic goal. Identification of genes that modulate healthspan, the period of mid-life vigor that precedes significant functional decline, will be an essential part of the effort to design anti-aging therapies. Because locomotory decline in humans is a major contributor to frailty and loss of independence and because slowing of movement is a conserved feature of aging across phyla, we screened for genetic interventions that extend locomotory healthspan of Caenorhabditis elegans.

From a group of 54 genes previously noted to encode secreted proteins similar in sequence to extracellular domains of insulin receptor, we identified two genes for which RNAi knockdown delayed age-associated locomotory decline, conferring a high performance in advanced age phenotype (Hpa). Unexpectedly, we found that hpa-1 and hpa-2 act through the EGF pathway, rather than the insulin signaling pathway, to control systemic healthspan benefits without detectable developmental consequences. Further analysis revealed a potent role of EGF signaling [to] promote healthy aging associated with low lipofuscin levels, enhanced physical performance, and extended lifespan.

This study identifies HPA-1 and HPA-2 as novel negative regulators of EGF signaling and constitutes the first report of EGF signaling as a major pathway for healthy aging. Our data raise the possibility that EGF family members should be investigated for similar activities in higher organisms.

In the present atmosphere of enthusiasm for manipulating metabolism to slow aging, I'm sure that the funding will be raised for further investigation. Now if we could just transfer some of that enthusiasm to the more productive and promising lines of research based upon periodic repair of the damage generated by metabolism rather than changing metabolism to slow down the rate at which damage is caused...

Iwasa H, Yu S, Xue J, & Driscoll M (2010). Novel EGF Pathway Regulators Modulate C. elegans Healthspan and Lifespan via EGF Receptor, PLC-gamma and IP3R Activation. Aging cell PMID: 20497132

A brace of popular science books on gerontology and engineered longevity have been written in past years - one of the many signs that the field is growing in profile in the public eye, an important step on the way to obtaining funding for more rapid progress. Here the Village Voice notes an irreverent forthcoming addition to the portfolio. Per the article, we probably shouldn't take it seriously as anything but a sign of the times: "Along with the origin of life and the nature of consciousness, why and how we age is one of the weightiest questions out there. It's one Weiner tackles in his new book Long for This World, a brilliant and improbably funny look inside the mind-bending science of immortality ... These people are asking what makes us mortal. It's something everyone's curious about, whether they're scientists or not. ... Human life expectancy has doubled over the past 200 years, Weiner writes, thanks primarily to advancements in medicine. And while prominent gerontologists argue that we can expect another seven years fairly soon, the most fervent members of the field are gunning for the total eradication of death. Chief among the latter is Aubrey David Nicholas Jasper de Grey, Weiner's arch protagonist."

Link: http://www.villagevoice.com/2010-05-25/books/jonathan-weiner-follows-search-for-immortality/

From Impact Aging earlier this year, an open access paper on some of the mechanics of hormesis: a little stress on your system improves longevity. "Oxidative stress constitutes the basis of physio-pathological situations such as neurodegenerative diseases and aging. However, sublethal exposure to toxic molecules such as reactive oxygen species can induce cellular responses that result in stress fitness. Studies in Schizosaccharomyces pombe have recently showed that the Sty1 MAP kinase, known to be activated by hydrogen peroxide and other cellular stressors, plays a pivotal role in promoting fitness and longevity when it becomes activated by calorie restriction, a situation which induces oxidative metabolism and reactive oxygen species production. Activation of the MAP kinase by calorie restriction during logarithmic growth induces a transcriptional anti-stress response including genes essential to promote lifespan extension. Importantly enough, the lifespan promotion exerted by deletion of the pka1 or sck2 genes, inactivating the two main nutrient-responsive pathways, is dependent on the presence of a functional Sty1 stress pathway, since double mutants also lacking Sty1 or its main substrate Atf1 do not display extended viability. ... We propose that moderate stress levels that are not harmful for cells can make them stronger."

Link: http://www.impactaging.com/papers/v2/n4/full/100133.html

Via Accelerating Future, I see that video of biomedical gerontologist Aubrey de Grey presenting at last year's TEDMED conference can be found at YouTube:

You can find coverage of TEDMED 2009 back in the archives here and at the Longevity Meme:

• Longevity Advocacy at TEDMED 2009 and BIL PIL
• TEDMED Day 1 Coverage
• TEDMED Day 2 Coverage

Also before lunch was the science of aging pair up with Aubrey de Grey, CSO of the SENS Foundation, and David Sinclair, professor at Harvard Medical School. If you've not heard of these gentlemen before, both view aging as a disease but both are approaching aging in very different ways. Aubrey spoke first and has a more futuristic view of aging. His mantra is that aging is metabolism caused cellular damage that leads to organism pathology, and the human body, just like cars, can be made to run longer with adequate maintenance and repair. He views age related problems as belonging to seven types and in order to tackle aging, all seven cellular and molecular problems need to be cured. Aubrey also coined the idea of a Longevity Escape Velocity (LEV), which is the point of life span where progress in aging science is occurring faster than the degradation of the body itself. He believes that if someone is able to live to 150 years old, then by that point the progress in the ability to keep them alive will be faster than their rate of death, thus they will live into their 1000s.

Some people do have better genes than others when it comes to a long life, though lifestyle choices do still seem to play a greater role. Here, researchers were looking to "determine whether offspring of parents with exceptional longevity (OPEL) have a lower rate of dementia than offspring of parents with usual survival (OPUS). ... [Participants were a] volunteer sample of 424 community-residing older adults without dementia aged 75 to 85 recruited from Bronx County starting in 1980 and followed for up to 23 years. ... Epidemiological, clinical, and neuropsychological assessments were completed every 12 to 18 months. OPEL were defined as having at least one parent who reached the age of at least 85. OPUS were those for whom neither parent reached the age of 85. ... The OPEL group had a lower incidence of Alzheimer's disease. After adjusting for sex, education, race, hypertension, myocardial infarction, diabetes mellitus, and stroke, results were essentially unchanged. OPEL also had a significantly lower rate of memory decline on the Selective Reminding Test (SRT) than OPUS. ... OPEL develop dementia and Alzheimer's disease at a significantly lower rate than OPUS. Demographic and medical confounders do not explain this result. Factors associated with longevity may protect against dementia and Alzheimer's disease."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20487085

Raised levels of heat shock proteins can protect against sarcopenia, age-related loss of muscle mass and strength: "HSP10 (Heat Shock Protein), helps monitor and organise protein interactions in the body, and responds to environmental stresses, such as exercise and infection, by increasing its production inside cells. Researchers [found] that excessive amounts of HSP10 inside mitochondria - 'organs' that act as energy generators in cells - can [preserve] muscle strength. ... We studied the role of HSP10 inside mitochondria, as it is here that unstable chemicals are produced which can harm parts of the cell. The damage caused by this is thought to play an important part in the ageing process, in which skeletal muscle becomes smaller and weaker and more susceptible to stress damage. In response to these stresses HSP10 increases its levels and helps cells resist damage and recover more effectively. Our research is the first to demonstrate that age-related loss of skeletal muscle mass is not inevitable." The article is sadly sensationalist, overhyping a slowing of muscle loss as "halting the aging process" when it is of course no such thing. It is unfortunate that university publicists feel the need to do this - it only makes them and the researchers they promote look foolish.

Link: http://www.physorg.com/news193913231.html

You might recall that researchers have in recent years demonstrated that antioxidants targeted to the mitochondria in your cells can boost life span in mice by around 20-30% or so. Per the mitochondrial free radical theory of aging, it may be supposed that these antioxidants are slowing the rate at which mitochondria damage themselves; that damage is the first step in a chain of consequences that leads to age-related degeneration and the failure of cells and bodily systems.

It is important to note that the use of mitochondrially targeted antioxidants is the only application of antioxidants shown to have any effect on longevity in mammals. For the most part, antioxidants do nothing, or may even harm long-term prospects for healthy longevity by interfering in the signaling processes of hormesis.

Amongst the researchers working on mitochondrial targeting of antioxidants are Rabinovitch, who used gene-engineering to boost mitochondrial levels of a natural antioxidant, and Skulachev, who has engineered an ingested antioxidant compound called SKQ1 that is taken up by the mitochondria - unlike any other form of ingested antioxidant.

A fellow emailed me today to let me know that SKQ1 is moving ahead in animal studies, now using dogs rather than mice. This is a common intermediate step on the way to early human trials:

Please be advised that trials of the mitochondially targeted antioxidant, SKQ1, are now underway in the canine model in both Moscow State Veterinary School and the St George Animal Hospital in Sydney. Early results have proven positive in a number of age related conditions.

I look forward to seeing the resulting papers when they are published.

Via EurekAlert!: "Cancer and diabetes – are risk factors the same for these two diseases? Or does diabetes cause processes in the body which promote the onset or growth of cancer? It is still unclear why diabetics have a higher rate of cancer than people who are not affected by this metabolic disorder. In order to precisely identify the types of cancer in which diabetes plays a role, [researchers carried out] the largest study ever on cancer risks of people with type 2 diabetes. The study included 125,126 Swedish citizens who had been hospitalized due to problems associated with type 2 diabetes. The epidemiologists compared the cancer incidence in these patients with that of the general population in Sweden. ... The researchers discovered that people with type 2 diabetes have an increased risk of developing 24 of the types of cancer studied. The most significant risk elevation was established for pancreatic and liver cell cancers. The rate of these cancers in people with type 2 diabetes is elevated by factor six and 4.25 respectively compared to the general population. The epidemiologists also found the risk of cancers of the kidneys, thyroid, esophagus, small intestine and nervous system to be more than twice as high." Diabetes is a very preventable condition - do the work, and you'll most likely avoid both it and the increased cancer risk that comes with it.

Link: http://www.eurekalert.org/pub_releases/2010-05/haog-icr052110.php

Artificial hearts have come a long way in recent years, but still have a long way to go to match the potential offered by tissue engineered organs: "For nearly two years, 43-year-old Charles Okeke has tried to live a normal life in the hospital tethered to a 400-lb. machine ... Okeke now has what is called a 'total artificial heart.' Both ventricles were removed along with four valves. Connector tubes were sewn in. It pumps blood just like a human heart. ... The FDA has just approved this backpack-sized device that runs on batteries and weighs just 13 lbs. It's the first portable technology to support the entire artificial heart. ... Sensors that used to be the size of a can of soup are now about the size of a quarter. That leap has enabled us to downsize the entire console. ... Charles will have to work hard to maintain his health as he awaits a new heart, but if the right match is not found, doctors say he could live indefinitely on this device. The Syncardia total artificial heart costs about $125,000 and about $18,000 a year to maintain."

Link: http://www.cbsnews.com/stories/2010/05/21/eveningnews/main6507572.shtml

Sarcopenia is the characteristic progressive loss of muscle mass and strength with age. Much like almost all other aspects of degenerative aging, sarcopenia is slowed by the practice of calorie restriction, but researchers are still debating the root causes of this process. Is sarcopenia a consequence of insulin resistance in any way, for example, or is it secondary to dietary changes that tend to happen later in life? Some researchers have compelling evidence to suggest that a progressive inability to process the essential amino acid leucine is what causes sarcopenia, and that the effect can be blunted by leucine supplementation and exercise. There is even debate as to whether the primary problem is loss of muscle mass or loss of function in the muscle fibers.

There is no shortage of other views. Here, researchers provide a convincing demonstration of their theory on sarcopenia:

Normally, [the tiny blood vessels in muscle] are closed, but when a young person eats a meal and insulin is released into the bloodstream, they open wide to allow nutrients to reach muscle cells. In elderly people, however, insulin has no such "vasodilating" effect.

"We were unsure as to whether decreased vasodilation was just one of the side effects of aging or was one of the main causes of the reduction in muscle protein synthesis in elderly people, because when nutrients and insulin get into muscle fibers, they also turn on lots of intracellular signals linked to muscle growth," said UTMB's Dr. Elena Volpi, senior author of the paper. "This research really demonstrates that vasodilation is a necessary mechanism for insulin to stimulate muscle protein synthesis."

Volpi and her collaborators reached this conclusion after an experiment in which they infused an amount of insulin equivalent to that generated by the body in response to a single meal into the thigh muscles of two sets of young volunteers. One group had been given a drug that blocked vasodilation, while the other was allowed to respond normally. Measurements of muscle protein synthesis levels where made using chemical tracers, while biopsies yielded data on specific biochemical pathways linked to muscle growth.

"We found that by blocking vasodilation, we reproduced in young people the entire response that we see in older persons - a blunting of muscle protein response and a lack of net muscle growth. In other words, from a muscle standpoint, we made young people look 50 years older," Volpi said.

The paper can be found via PubMed for those who are interested. Blood vessels are an important form of biological infrastructure in our bodies: not just tubes, but in fact complex reactive machinery. They become progressively more damaged by age, unable to adjust as they should, and this causes harm to many of our bodily systems:

The rust that causes blood vessels to degrade in performance probably has to do with increasing oxidative damage, the accumulation of AGE compounds that interfere in cell signaling, and possibly the chemistry of chronic inflammation. Blood vessels are complex little machines that rely on their structure and a coordinated set of signaling mechanisms to do their job. As the damage of aging changes that structure, interferes with signaling, and degrades the effectiveness of our blood vessels, this in turn hurts the rest of our biochemical systems.

Timmerman KL, Lee JL, Dreyer HC, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Sheffield-Moore M, Rasmussen BB, & Volpi E (2010). Insulin Stimulates Human Skeletal Muscle Protein Synthesis via an Indirect Mechanism Involving Endothelial-Dependent Vasodilation and Mammalian Target of Rapamycin Complex 1 Signaling. The Journal of clinical endocrinology and metabolism PMID: 20484484

From the SENS Foundation: "Aggregates of beta-amyloid (Abeta) and other malformed proteins accumulate in brain aging and neurodegenerative disease, leading progressively to neuronal dysfunction and/or loss. The regenerative engineering solution to these insults is therapeutic clearance of aggregates, extracellular (such as Abeta plaques) and intracellular (such as soluble, oligomeric Abeta). Immunotherapeutic Abeta clearance from the brain is a very active field of Alzheimer's research, with at least seven passive, and several second-generation active, Abeta vaccines currently in human clinical trials ... One challenge to optimal vaccine design is matching the specificity of antibodies the range of Abeta aggregates that form in vivo ... agents that sequester one Abeta species may leave other species intact, and in some cases a shift in assembly dynamics can actually promote the formation of one species while clearing or reducing the formation of others ... Although in very early in vivo testing, a new approach has emerged that may offer that promise. This is the use of an Abeta-targeting affibody, i.e., a novel non-immunoglobulin binding protein generated through combinatorial protein engineering."

Link: http://www.sens.org/node/785

Via EurekAlert!: "excess abdominal fat places otherwise healthy, middle-aged people at risk for dementia later in life. ... [The study] included 733 community participants who had a mean age of 60 years with roughly 70% of the study group comprised of women. Researchers examined the association between Body Mass Index (BMI), waist circumference, waist to hip ratio, CT-based measures of abdominal fat, with MRI measures of total brain volume (TCBV), temporal horn volume (THV), white matter hyperintensity volume (WMHV) and brain infarcts in the middle-aged participants. ... Our results confirm the inverse association of increasing BMI with lower brain volumes in older adults and with younger, middle-aged adults and extends the findings to a much larger study sample. ... Prior studies were conducted in cohorts with less than 300 participants and the current study includes over 700 individuals. ... More importantly our data suggests a stronger connection between central obesity, particularly the visceral fat component of abdominal obesity, and risk of dementia and Alzheimer's disease ... the association between VAT and TCBV was most robust and was also independent of BMI and insulin resistance. Researchers did not observe a statistically significant correlation between CT-based abdominal fat measures and THV, WMHV or BI."

Link: http://www.eurekalert.org/pub_releases/2010-05/w-afa051910.php

The Gerontology Research Group mailing list is presently hosting a healthy discussion on the question of whether or not aging is a disease - no doubt touched off by this article in the UK press:

"If aging is seen as a disease, it changes how we respond to it. For example, it becomes the duty of doctors to treat it," said David Gems, a biogerontologist who spoke at a conference on aging in London last week called "Turning Back the Clock."

At the moment, drug companies and scientists keen to develop their research on aging into tangible results are hampered by regulators in the United States and Europe who will license medicines only for specific diseases, not for something as general as aging.

"Because aging is not viewed as a disease, the whole process of bringing drugs to market can't be applied to drugs that treat aging. This creates a disincentive to pharmaceutical companies to develop drugs to treat it," said Gems.

As you might already know, whether or not aging is called a disease has very little to do with words and definitions, and a great deal to do with money and regulation. Unelected officials of organizations like the FDA in the United States cause untold harm to progress in medical science by (a) placing huge and unnecessary burdens upon research and development, and (b) forbidding outright commercial application for any purpose or disease that is not in their list. It can take a decade - and millions of dollars in the formalized bribery known as lobbying - for a new discovery, new classification, or new form of therapy to be recognized by regulators. Or even longer, as is the case for aging.

A world without the FDA would be a far better place, in which progress was faster and the breadth of medical development far greater. The death toll of those who wait in vain for new and more effective therapies would be greatly reduced, and the engines of free market competition turned to building new medical miracles. But sadly we do not live in that world - it lies somewhere beyond the next revolution, or perhaps beyond the next great open frontier.

Another paper looks at some of the consequences of becoming obese. In a more fair and productive world, medical costs would be an individual responsibility rather than being socialized as they are at present: "The prevalence of adult obesity has increased in recent decades. It is important to predict the long-term effect of body weight, and changes in body weight, in middle age on longevity and Medicare costs in older ages. ... We predicted longevity and lifetime Medicare costs via simulation for 45-year-old persons by body weight in 1973 and changes in body weight between 1973 and 1983. ... Obese 45-year-olds had a smaller chance of surviving to age 65 and, if they did, incurred significantly higher average lifetime Medicare costs than normal-weight 45-year-olds ($163,000 compared with $117,000). Those who remained obese between ages 45 and 55 in 1973 to 1983 incurred significantly higher lifetime Medicare costs than those who maintained normal weight. ... Chronic obesity in middle age increases lifetime Medicare costs relative to those who remained normal weight. As the survival of obese persons improves, it is possible that Medicare costs may rise substantially in the future to meet the health care needs of today's obese middle-aged population."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20473195

From the Technology Review: "Support cells in the brain called astroglia can be turned into functioning neurons. ... Researchers found that they could transform the cells into two different classes of neurons, and that the neurons could form connections with one another in a dish. Although the research is at an early stage, the finding suggests that scientists could someday recruit existing cells in the brain to repair the brain and spinal cord after a stroke, injury, or neurodegenerative disease. ... The addition of one specific gene generated excitatory neurons, which promote activity in other cells. By adding a different gene, they generated inhibitory neurons, which dampen cell activity. In principle, [you] could generate other types of neurons if you choose the appropriate factors ... The study adds to growing evidence that certain cell types can be transformed directly into other cell types without first being converted into stem cells. ... one of the next challenges is to determine whether these reprogrammed neurons can survive and function in a living brain. Fortunately, the brain seems to have a ready source of astroglia. When the brain is injured, these cells proliferate, similar to the way the skin repairs itself after a wound. The researchers found they could also derive neurons from injury-induced astroglia taken from the brains of adult mice."

Link: http://www.technologyreview.com/biomedicine/25353/

Researchers interested in metabolic manipulation as a path to extended healthy longevity continue to identify potential compounds to feed into the long drug development process. Many such compounds begin with worm or fly life span studies, as the major known genes associated with metabolism and life span are conserved between species - all the way from worms up to we humans. If a compound can make a fly live longer and can be shown to act on genes and mechanisms already associated with calorie restriction or insulin metabolism, then you'll probably see interest in pushing forward to testing in mammals.

Here is an example of this sort of research:

Trehalose is a disaccharide of glucose found in diverse organisms and is suggested to act as a stress protectant against heat, cold, desiccation, anoxia, and oxidation.

Here, we demonstrate that treatment of [nematode worms of the species] Caenorhabditis elegans with trehalose starting from the young-adult stage extended the mean life span by over 30% without any side effects. Surprisingly, trehalose treatment starting even from the old-adult stage shortly thereafter retarded the age-associated decline in survivorship and extended the remaining life span by 60%. Demographic analyses of age-specific mortality rates revealed that trehalose extended the life span by lowering age-independent vulnerability. Moreover, trehalose increased the reproductive span and retarded the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin.

...

The life span-extending effect of trehalose was abolished in long-lived insulin/IGF-1-like receptor (daf-2) mutants. ... These findings indicate that a reduction in insulin/IGF-1-like signaling extends lifespan, at least in part, through the aging-suppressor function of trehalose. Trehalose may be a lead compound for potential nutraceutical intervention of the aging process.

Manipulation of insulin signaling is how the present winner of the Mprize for longevity science produced a mouse that lived 60-70% longer than normal. So we might expect to see some effect on longevity in mice from trehalose when researchers raise funding and perform the studies.

Honda Y, Tanaka M, & Honda S (2010). Trehalose extends longevity in the nematode Caenorhabditis elegans. Aging cell PMID: 20477758

From h+ Magazine: "A new study [sheds] some light on how 'memory disturbances' in an aging mouse brain are associated with altered 'hippocampal chromatin plasticity' - the combination of DNA, histones, and other proteins that make up the chromosomes associated with the hippocampus. Specifically, the study describes an acetyl genetic switch that produces memory impairment in aging 16-month-old mice. Because the acetyl wasn't present in young 3-month-old mice, the study concludes that it acts as a switch for a cluster of learning and memory genes. ... when young mice are learning, an acetyl group binds to a particular point on the histone protein. The cluster of learning and memory genes on the surrounding DNA ends up close to the acetyl group. This acetyl group was missing in the older mice that had been given the same tasks. By injecting an enzyme known to encourage acetyl groups to bind to any kind of histone molecule, [researchers] flipped the acetyl genetic switch to the 'on' position in the older mice and their learning and memory performance became similar to that of 3-month-old mice. ... [Researchers hope] that the study of hippocampal chromatin plasticity and gene regulation in mice will help them to identify therapeutic strategies to encourage neuroplasticity (the formation of new neural networks in the brain), to improve learning behavior, and to recover seemingly lost long-term memories in human patients."

Link: http://www.hplusmagazine.com/articles/neuro/switch-memory

Via EurekAlert!: "Two methods of extending life span have very different effects on memory performance and decline with age. ... While the nematode C. elegans is already well known for its utility in longevity research, previously it was not known how the memory of C. elegans compares with that of other animals, or whether longevity treatments could improve learning and memory. To answer these questions, [researchers] designed new tests of learning and memory in C. elegans, then used these tests to identify the necessary components of learning, short-term memory, and long-term memory. They found that the molecules required for learning and memory appear to be conserved from C. elegans to mammals, suggesting that the basic mechanisms underlying learning and memory are ancient. The authors also determined how each of the behaviors declines with age, and tested the effects of two known regulators of longevity - dietary restriction and reduced Insulin/IGF-1 signaling - on these declines. Surprisingly, very different effects on memory were achieved with the two longevity treatments: dietary restriction impaired memory in early adulthood but maintained memory with age, while reduced Insulin/IGF-1 signaling improved early adult memory performance but failed to preserve it with age. These results suggest not only that longevity treatments could help preserve cognitive function with age, but also that different longevity treatments might have very different effects on such declines."

Link: http://www.eurekalert.org/pub_releases/2010-05/plos-pmw051210.php

Reliability theory is, put very simply, a way of modeling and predicting the failure modes and mean time to failure of complex systems with many redundant parts subject to wear and tear. Reliability theory has seen a great deal of use in the electronics industry, amongst many others, but the human body is also a complex system that can be considered in these terms. Looking at our life spans and age-related illnesses in the context of reliability theory and the accumulating failure of redundant systems can add a great deal to our understanding of aging and our expectations for longevity science.

In recent years there has been more interest in this topic amongst aging researchers. I'm sure that Leonid Gavrilov and Natalia Gavrilova, who produced some of the important papers in this space, will be pleased to see that more researchers are now rigorously applying reliability theory to aging and longevity:

Aging in mouse brain is a cell/tissue-level phenomenon exacerbated by proteasome loss

Biological aging is often described by its phenotypic effect on individuals. Still, its causes are more likely found on the molecular level. Biological organisms can be considered as reliability-engineered, robust systems and applying reliability theory to their basic non-aging components, proteins, could provide insight into the aging mechanism.

Reliability theory suggests that aging is an obligatory trade-off in a fault-tolerant system such as the cell which is constructed based on redundancy design. Aging is the inevitable redundancy loss of functional system components, that is proteins, over time. In our study we investigated mouse brain development, adulthood and aging from embryonic day 10 to 100 weeks. We determined redundancy loss of different protein categories with age using reliability theory. We observed a near-linear decrease of protein redundancy during aging.

Aging may therefore be a phenotypic manifestation of redundancy loss caused by non-functional protein accumulation. This is supported by a loss of proteasome system components faster than dictated by reliability theory. This loss is highly detrimental to biological self-renewal and seems to be a key contributor to aging and therefore could represent a major target for therapies for aging and age-related diseases.

Proteins are the cogs, building blocks, and tools of your cells and the machines inside your cells. Without all the specific proteins needed, cells and cellular components become dysfunctional, fail, or die. If you look through the contributions to aging outlined in the Strategies for Engineered Negligible Senescence, you'll see numerous ways in which malformed or damaged proteins can increase greatly in number across a life span - often indirectly as an end result of a chain of other forms of failure and damage in cellular machinery.

Mao L, Roemer I, Nebrich G, Klein O, Koppelstaetter A, Hin SC, Hartl D, & Zabel C (2010). Aging in mouse brain is a cell/tissue-level phenomenon exacerbated by proteasome loss. Journal of proteome research PMID: 20469937

Researchers here demonstrate that comparatively simple stem cell transplants may be effective in regenerating lung injuries: "Human stem cells administered intravenously can restore alveolar epithelial tissue to a normal function in a novel ex vivo perfused human lung after E. coli endotoxin-induced acute lung injury (ALI) ... ALI is a common cause of respiratory failure in the intensive care units, often leading to death. It can be caused by both direct injury such as aspiration and pneumonia, and indirect injury such as sepsis and from trauma. ... Yearly, ALI affects approximately 200,000 patients in the US and has a 40 percent mortality rate despite extensive investigations into its causes and pathophysiology. Innovative therapies are desperately needed. ... we found that intravenous infusion of [stem cells] preferentially homed to the injured areas of the lung, which means that the cells find their way from the bloodstream to the sites in the lung of injury. ... In addition to having restored function of alveolar epithelial cells, lungs treated with [stem cells] showed a reduction in inflammatory [cytokine] levels suggesting a favorable shift away from a proinflammatory environment in the injured alveolus."

Link: http://www.eurekalert.org/pub_releases/2010-05/ats-scr051010.php

From the Guardian: "The human body has tremendous capacity to repair itself after disease or injury. Skin will grow over wounds, while cells in our blood supply are constantly being manufactured in our bone marrow. But there is a limit to the body's ability to replace lost tissue. Cartilage cells are notoriously poor at regrowing after injury, for example. As a result, accidents and illnesses - including cancers - often leave individuals with disfiguring wounds or life-threatening damage to tissue. The aim of Molly Stevens, a nanoscience researcher at Imperial College, London, and founder of the biotech firm Reprogen, is a simple but ambitious one. Working with a team of chemists, cell biologists, surgeons, material scientists and engineers, she is developing techniques that will help the body repair itself when it suffers damage. This is the science of regenerative medicine. ... One approach that we have had considerable success with involves taking quite straightforward materials including simple polymers and using them to boost bone growth in a person. We made them into gels that we could inject into bones. The key to this technique lies with the fact that our bones are covered in a layer of stem cells. We inject our material under that layer and that wakes up those stem cells. They start to multiply and produce lots of new bone."

Link: http://www.guardian.co.uk/technology/2010/may/16/bright-idea-get-body-grow-spare-parts

Filmmaker Woody Allen is a reliable source of pithy quotes on the topic of death, and I see that many are being pulled forth from the drawer on the occasion of his latest movie. Perhaps the best known can even be found on one of the older pages at the Longevity Meme:

I don't want to achieve immortality through my work; I want to achieve it through not dying.

Or alternatively:

I dont want to live on in my work, I want to live on in my apartment!

And this, which comes right to the point:

"My relationship with death remains the same as ever," Allen quipped at the press conference. "I'm strongly against it."

Which is nothing more than sanity in the face of the ugly reality of the human condition - that our lives are presently limited through no fault of our own, and that we suffer and we end when we what we really want is to continue in good health to see another tomorrow. Fundamentally, the entirety of the modern healthy life extension community springs from this simple and obvious opinion, shared amongst its members: to be strongly against death.

You who read this today are, I hope, strongly against death. But what are you doing about it?

Researchers have regrown teeth in rats by manipulating existing stem cells: "a new technique [can] orchestrate the body's stem cells to migrate to three-dimensional scaffold that is infused with growth factor. This can yield an anatomically correct tooth in as soon as nine weeks once implanted in the mouth. ... These findings represent the first report of regeneration of anatomically shaped tooth-like structures in vivo, and by cell homing without cell delivery. ... By homing stem cells to a scaffold made of natural materials and integrated in surrounding tissue, there is no need to use harvested stem cell lines, or create a an environment outside of the body (e.g., a Petri dish) where the tooth is grown and then implanted once it has matured. The tooth instead can be grown 'orthotopically,' or in the socket where the tooth will integrate with surrounding tissue in ways that are impossible with hard metals or other materials. ... A key consideration in tooth regeneration is finding a cost-effective approach that can translate into therapies for patients who cannot afford or who aren't good candidates for dental implants. Cell-homing-based tooth regeneration may provide a tangible pathway toward clinical translation."

Link: http://www.dentistryiq.com/index/display/article-display/0045494294/articles/dentisryiq/industry/2010/05/body_s-stem_cells.html

From the Max Planck Institute: "Marriage is more beneficial for men than for women - at least for those who want a long life. Previous studies have shown that men with younger wives live longer. While it had long been assumed that women with younger husbands also live longer, [a new study] has shown that this is not the case. Instead, the greater the age difference from the husband, the lower the wife's life expectancy. This is the case irrespective of whether the woman is younger or older than her spouse. ... The mortality risk of a husband who is seven to nine years older than his wife is reduced by eleven percent compared to couples where both partners are the same age. Conversely, a man dies earlier when he is younger than his spouse. For years, researchers have thought that this data holds true for both sexes. They assumed an effect called 'health selection' was in play; those who select younger partners are able to do so because they are healthier and thus already have a higher life expectancy. ... These theories now have to be reconsidered. It appears that the reasons for mortality differences due to the age gap of the spouses remain unclear."

Link: http://www.demogr.mpg.de/en/press/1813.htm

The theory that cancers spawn from and are supported by a comparatively small population of characteristically broken stem cells has enjoyed some success in recent years. By uncovering and attacking cancer stem cells using a new generation of precisely targeted therapies, scientists hope that cancer might be defeated with far less trouble and cost than in the past. Despite promising research results, this is still a hotly debated topic, and on the other side of the fence can be found good evidence to oppose the existence of cancer stem cells. But you might want to look back in the archives for an introduction to the topic first:

• A Few Cancer Stem Cell Articles
• The Cancer Stem Cell Theory Continues to Look Promising
• The Skeptical View of Cancer Stem Cells
• Clonal Evolution or Cancer Stem Cells?

If you're ready to continue, let me point you to disappointing evidence from researchers investigating the biology of melanomas - which look to be 100% cancer stem cell masses, meaning there are few immediate prospects for a short-cut in destroying these cells run riot:

The researchers write in the May 14 issue of the journal Cell that - contrary to other published reports - melanoma does not appear to follow the hierarchic cancer stem cell model, where a single malignant "mother cell" both reproduces to produce new mother cells and differentiates to produce the bulk tumor population. Instead, all melanoma cells equally harbor cancer stem cell potential and are capable of inducing new tumors. Their findings reveal the unique biology of melanoma, and suggest that melanoma requires a new therapeutic approach.

"Targeting only the bulk tumor population, as most conventional anticancer therapies do, is pointless in melanoma, in that each cell can act as a seed for the tumors to rebound," said Meenhard Herlyn, D.V.M., D.Sc., professor and leader of Wistar's Molecular and Cellular Oncogenesis Program. "The other implication is that we should stop hunting for a cancer stem cell, because it won't be there."

...

At the moment, the researchers do not suggest that the cancer stem cell model is wrong in any other tumors; their results apply only to melanoma, which may represent a special case.

We can hope that this is a special case - though if one form of cancer can do this, there is every reason to expect that some other types do so as well.

A new technique for tissue engineering: "Tissue engineering has long held promise for building new organs to replace damaged livers, blood vessels and other body parts. However, one major obstacle is getting cells grown in a lab dish to form 3-D shapes instead of flat layers. ... To obtain single cells for tissue engineering, researchers have to first break tissue apart, using enzymes that digest the extracellular material that normally holds cells together. However, once the cells are free, it's difficult to assemble them into structures that mimic natural tissue microarchitecture. Some scientists have successfully built simple tissues such as skin, cartilage or bladder on biodegradable foam scaffolds. ... That works, but it often lacks a controlled microarchitecture. You don't get tissues with the same complexity as normal tissues. ... Researchers [have] come up with a new way to overcome that challenge, by encapsulating living cells in cubes and arranging them into 3-D structures, just as a child would construct buildings out of blocks. The new technique, dubbed 'micromasonry,' employs a gel-like material that acts like concrete, binding the cell 'bricks' together as it hardens. ... You can reproduce this in any lab. It's very simple. ... The short-term next step is really looking at different cell types and the viability of tissue growth."

Link: http://web.mit.edu/newsoffice/2010/tissue-legos-0513.html

Via EurekAlert: "Humans are born with 30,000 cochlear and vestibular hair cells per ear. (By contrast, one retina harbors about 120 million photoreceptors.) When a significant number of these cells are lost or damaged, hearing loss occurs. The major reason for hearing loss and certain balance disorders is that - unlike other species such as birds - humans and other mammals are unable to spontaneously regenerate these hearing cells. ... After years of lab work, researchers [have] found a way to develop mouse cells that look and act just like the animal's inner-ear hair cells - the linchpin to our sense of hearing and balance - in a petri dish. If they can further perfect the recipe to generate hair cells in the millions, it could lead to significant scientific and clinical advances along the path to curing deafness in the future. ... While researchers will ultimately need human hair cells, the mouse version is a good model for the initial phases of experimentation, he said. In addition to using mouse embryonic stem cells, the researchers used fibroblasts that had been reprogrammed to behave like stem cells: These are known as induced pluripotent stem cells, or iPS cells."

Link: http://www.eurekalert.org/pub_releases/2010-05/sumc-at051010.php

A large merged double edition of the journal Rejuvenation Research is now online, bringing with it a lot of papers to look through. I thought I'd direct your attention to one of those many papers, as it presents an interesting evolutionary background to the SENS approach to the mitochondrial DNA damage that accumulates with age.

Our mitochondria are biological power plants within our cells, the evolved descendants of symbiotic bacterial species. They convert food into ATP, the chemical used as fuel by cells. Mitochondria have their own DNA, a relic left over from when they were some form of free-living species. Over time, portions of that mitochondrial DNA have become incorporated into our own nuclear DNA at the heart of the cell. By evolutionary considerations, these changes must have prospered and spread because they provided some form of advantage. One thing to consider in this respect is that nuclear DNA is far better protected from damage than mitochondrial DNA. Indeed, one root cause of aging is that our mitochondrial DNA is battered over the years by side-effects of the chemical reactions that produce ATP. This is not a problem suffered by nuclear DNA to anywhere near the same degree.

So what is the result of more mitochondrial DNA showing up in the armored cell nucleus? As it turns out, there is a good argument that the result is a longer life. The researchers here find a strong correlation between more mitochondrial DNA in the nucleus and longer life span for a species:

NUMT ("New Mighty") Hypothesis of Longevity

Maximum life span (MLS) and abundance of mitochondrial DNA (mtDNA) insertions in the nuclear DNA (NUMTs) were analyzed in 17 animal species with completely sequenced mitochondrial and nuclear genomes. Highly significant positive correlations were found between MLS and NUMT number, total size, or density (both in mammals and all animal species).

This is most interesting when you consider that the SENS approach to removing the contribution of mitochondrial DNA damage to aging is exactly this: copy the remaining vital mitochondrial genes into our nuclear DNA. If the necessary proteins encoded by these genes are still being produced by the cell and delivered to the mitochondria even after the mitochondrial gene is somehow damaged, then that damage will have no effect.

Muradian, K., Lehmann, G., & Fraifeld, V. (2010). NUMT (“New Mighty”) Hypothesis of Longevity Rejuvenation Research, 13 (2-3), 152-155 DOI: 10.1089/rej.2009.0974

From the SENS Foundation: "To date, all successful interventions into the biological aging process in experimental animals have entailed modulation of basic metabolic pathways, generally through genetic or dietary manipulation. Of these, the earliest, most well-studied, and arguably the most robust, is Calorie restriction (CR): the reduction in dietary energy intake, without compromise of essential nutrients. With few exceptions, CR retards the biological rate of aging in nearly every species and strain of organisms in which it has been tested, ranging from rotifers, through small multicellular invertebrates, and most extensively to laboratory rodents; and although inconclusive, recent evidence also supports its effectiveness in dogs and nonhuman primates. Moreover, while necessarily preliminary, a growing body of human research has reported that rigorous CR, when practiced by previously normal-weight adults, results in physiological, functional, and perhaps even structural changes consistent with its translation to the human case. ... But despite the initial attractiveness of the notion; its strong theoretical basis; the high level of scientific interest that it has garnered; the launching of biotech startups originating in CR mimetic research; and the popularization and commercial exploitation of the concept by the dietary supplement industry - despite all of these drivers, the ensuing decade and a half or more of CR mimetic research have thus far been fruitless. Initially-promising compounds have failed to extend lifespan, while surprising findings have preempted the further investigation of what might otherwise have been novel targets for CR mimetics."

Link: http://www.sens.org/node/777

From QFinance: "Big business and governments are already grappling with the uncomfortable side effects of increasing longevity. According to actuaries, the present generation has gained the equivalent of 12 minutes an hour or a 20% increase in average lifespan by comparison with the previous generation. The impact of this is felt first and foremost in the pensions arena, with businesses having to run harder just to stand still as far as their pension scheme deficits are concerned. But it is felt too by governments across Europe as they struggle to pay out meaningful state pension benefits against the headwind imposed by the fact that the ratio of those in work to those on pension is getting more and more out of balance. The impact of increased longevity is felt too in the health systems, where the diseases and ailments of old age take an increasing toll on a country's medical resources. These problems might seem fairly intractable, or at least extremely difficult and challenging in their own right, but it could be just the tip of the iceberg, according to the renowned longevity specialist Dr Aubrey de Grey, Chief Scientist at the charity SENS, which specializes in promoting research that aims to 'defeat ageing.' Dr de Grey is famous for asserting that the first person to enjoy a four-digit lifespan is probably already in his or her middle years. Before I give a rapid summary of his reasoning - those interested in learning more can watch a video of one of his presentations at the SENS website - it is worth saying that if de Grey is right, then instead of exacerbating the pensions problem, as I suggested earlier, it will probably make the problem vanish like a puff of smoke. Provided society stays reasonably open, people will have more than enough time to acquire independent means. The magic of compound arithmetic will be very much in their favor. Start small, watch it grow, where's the hurry?"

Link: http://www.qfinance.com/blogs/anthony-harrington/2010/05/05/the-challenge-of-longevity

As you might know, the Royal Society recently held a meeting on "the new science of aging." Amongst those attending was researcher Nir Barzilai, who has been investigating genetics and metabolism associated with human longevity for some years. One example is his work with long-lived members of the Ashkenazi Jewish population. The UK press recently published a short interview with Barzilai:

[Barzilai] studied 500 Jewish people between 95 and 112. He said: "These people smoked, they are overweight, they have high cholesterol." Qualifying his remarks, he said about 30 per cent of them were obese, while 30 per cent of them had smoked to the age of 95. "They are protected from the environment by their genotype," he said. Living a healthy life might help most people increase their life expectancy by a few years, but it would not help those who wanted to live much longer, he said.

...

"When they eventually die, they die of the same things that people die of in their 70s or 80s," he said, "it's just that they die 30 years later". Identifying these genes opened the doorway to developing longevity drugs which mimicked their effects, he said.

Prof Barzilai and his team have already identified a number of such genes among the centenarians. Laboratories are now working on creating a drug which mimics the effects of three of them - two that increase the production of so-called 'good' cholesterol in the body, which reduces the risk of heart disease and stroke, and a third that helps prevent diabetes. Testing could begin by 2012, he said, with it appearing on the market "within five or 10 years".

He predicted: "People will take a pill, starting at 40, and their lives will be longer."

This is, in a nutshell, the goal of the dominant camp in gerontology: a long-term project to incrementally push out the average human life span much closer to what is presently the maximum. This will be accomplished through the existing institutional processes of drug discovery and development, producing and commercializing treatments that can interfere with the operation of human metabolism and push it into more advantageous configurations.

This is also the slow path to a poor end goal, as I've argued many a time in the past. It won't do much to help those people already old when the therapies arrive. The researchers who work on this strategy are doing so because they don't believe there is a better way forward. Fortunately they are wrong. Unfortunately, comparatively few people are working on better projects, based on ongoing periodic repair of cellular and biochemical damage rather than changing metabolism to slow down damage accumulation. But if you've been following along at home, you know all this already.

Here is another important quote from the article:

He also argued that ageing itself needed to be classed as a disease, in order to stimulate investment in drugs which delayed a range of age-related diseases.

As you may or may not be aware, regulatory bodies such as the FDA in the US forbid the treatment of aging. They do this by means of only approving treatments for named and defined diseases, and not considering aging or any of its root causes to be a disease. This is an enormous problem, even compared to the vast damage the FDA does to other areas of medical science simply by existing. When people are forbidden by law from selling a treatment for aging, then there will be few investors lining up to fund research and development of promising science. We will never know just how much farther advanced the science of engineered longevity might be today if the FDA and its counterparts elsewhere in the world didn't exist.

An open access paper from Impact Aging: "The Mitochondrial Free Radical Theory of Aging (MFRTA) is currently one of the most widely accepted theories used to explain aging. From MFRTA three basic predictions can be made: long-lived individuals or species should produce fewer mitochondrial Reactive Oxygen Species (mtROS) than short-lived individuals or species; a decrease in mtROS production will increase lifespan; and an increase in mtROS production will decrease lifespan. It is possible to add a further fourth prediction: if ROS is controlling longevity separating these parameters through selection would be impossible. These predictions have been tested in Drosophila melanogaster." Where I think the researchers go wrong here lies in not accounting for how differences in mitochondrial composition might affect the level of damage caused by a given amount of ROS. There is a strong argument that species life span differences have a lot to do with how resilient mitochondria are to damage. But read the paper anyway; it's a good introduction to thinking about the mitochondrial free radical theory of aging.

Link: http://www.impactaging.com/papers/v2/n4/full/100137.html

As this Independent article shows, the public view of longevity science extends little beyond the goal of slowing aging espoused by mainstream researchers, and conflates the fakery and fraud of "anti-aging" cosmetics companies with real science: "We spend millions of pounds each year on anti-ageing tonics, potions, vitamins and creams, trying to stave off the ravages of the years. But our genetic inheritance trumps all other factors in determining how well we age and how long we live. By unravelling the genetic determinants of longevity, scientists believe they will be able to manipulate them to add not only years to life, but also life to years. An elixir of youth remains a distant dream but medicines to help us live longer and better are moving closer. At a conference this week, Turning Back the Clock, organised by the Royal Society, researchers described the progress that has been made in the science of ageing. At least 10 gene mutations have been identified that extend the lifespan of mice by up to half, and in humans several genetic variants have been linked with longevity. They include a family of genes dubbed the sirtuins, which one Italian study found occurred more commonly in centenarian men than in the general population. A subsidiary of drug giant GlaxoSmithKline is now looking at sirtuins, and their association with a range of age-related diseases including type 2 diabetes and cancers."

Link: http://www.independent.co.uk/news/science/has-the-elixir-of-youth-come-of-age-1971341.html

The Longevity Consortium is an interesting project, and its members are a representative cross-section of the mainstream of modern aging research - which is to say people who largely focus on understanding aging only, or on slowing aging by manipulating metabolism. From the Consortium website:

We are a consortium of scientists from multiple disciplines interested in the study of genetics of aging and age-related traits. Our group includes laboratory-based scientists, epidemiologists and statistical geneticists.

Members of the Consortium represent three types of research efforts:

• Laboratories devoted to the identification of longevity-related genes and pathways in non-human species;
• Studies of special populations (e.g., centenarians) that are engaged in the discovery of genes associated with longevity; and
• Established longitudinal cohorts of elderly men and women that have DNA and excellent phenotyping that can be used to study candidate genes.

As you all no doubt know by now, I'm no fan of efforts aimed exclusively at slowing down aging through genetic or metabolic alteration. These are slow, hard, and complex paths that will lead to poor results in comparison to repair-focused strategies like SENS. A method of slowing aging that arrives thirty years from now will be largely worthless for those of us presently in middle age - we'll already be old and damaged. But a method of repair that can reverse that damage is another story entirely, and furthermore can be used over and again whenever damage reappears. So if we have thirty years to work on this problem, why not work on producing a solution that will actually help?

But I digress.

As I've mentioned in the past, this is an age of synthesis in the life sciences. Fields are huge, fragmented, and far too expansive for any one researcher to discover everything that might be important to his or her work. Related projects often take place in unknowing isolation - but collaboration would lead to faster progress and greater insight on all sides. There is a great need for more in the way of institutions and processes that aim to knit back together the diverse fields and research groups that would benefit from closer ties, and make it possible for researchers to easily discover all the relevant ongoing work that relates to their current studies. In this, at least, the Longevity Consortium is pointed in the right direction:

Investigators in longevity have behaved a bit like separate species. There has been intense scientific intercourse among those working with invertebrates, or with centenarians, or those working on chronic diseases in the elderly, but virtually no contact between these groups. The Consortium will bring together these diverse groups of investigators to develop useful tools, such as a catalogue of polymorphisms in candidate genes that have been associated with longevity in other species, including those that may arise from the DNA microarray analyses of primate tissues that are part of this proposal. It will produce a searchable Website of publications, abstracts, and key resources for the field and an electronic forum for exchange of unpublished ideas and findings. The phenotypes of longevity and frailty developed by this Consortium will help establish common approaches in this area. The Consortium will engage several large longitudinal cohorts of older adults in longevity research, introducing them to experts in longevity with the expectation that these cohorts will provide adequate sample sizes to study candidate genes, thereby avoiding under-powered negative studies and enabling the rapid confirmation of candidates discovered in laboratories and special populations. If naturally occurring alleles that influence longevity are uncommon or if they have modest effects, then studies to identify and confirm longevity genes must involve the power of these large populations.

There are actually a fair few interesting resources at the Consortium site or linked from it. You should wander through and take a look.

Another consequence of the overeating and lack of exercise that leads to metabolic syndrome and diabetes: "In people with insulin resistance or full-blown diabetes, an inability to keep blood sugar levels under control isn't the only problem by far. A new report [shows] that our arteries suffer the effects of insulin resistance, too, just for entirely different reasons. ... Earlier studies showed that in the context of systemic insulin resistance, blood vessels become resistant, too. Doctors also knew that insulin resistance and the high insulin levels to which it leads are independent risk factors for vascular disease. But it wasn't clear if arteries become diseased because they can't respond to insulin or because they get exposed to too much of it. Now comes evidence in favor of the former explanation. ... mice prone to atherosclerosis fare much worse when the linings of their arteries can't respond to insulin. The animals' insulin-resistant arteries develop plaques that are twice the size of those on normal arteries. Insulin-resistant blood vessels don't open up as well, and levels of a protein known as VCAM-1 go up in them, too. VCAM-1 belongs to a family of adhesion molecules [which sit on the endothelium and bind] white blood cells. ... Those cells can enter the artery wall, where they start taking up cholesterol, and an early plaque is born. ... The results provide definitive evidence that loss of insulin signaling in the endothelium, in the absence of competing systemic risk factors, accelerates atherosclerosis."

Link: http://www.eurekalert.org/pub_releases/2010-05/cp-yam042810.php

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."

Link: http://www.eurekalert.org/pub_releases/2010-05/rup-mtc050610.php

The growth in health, welfare, and wealth of 18th century Europe was a glittering spire when set against any measure of the grand history of humanity. A pinnacle set abruptly at the end of a very long, very gentle upward slope. Consider that, as noted at In Search of Enlightenment:

Prehistoric human remains have never revealed individuals older than about 50 years of age, and humans had a life expectancy at birth of 30 years or less for more than 99.9% of the time that we have inhabited this planet.

Disease, parasitism, pain, suffering, and a short life is the unvarnished and absolutely natural human condition, absent our marvelous talent for progress. That talent, compounded over the course of history, ensured that the 18th century was a time of great change and increasing life spans. But by the year 1900, those earlier heights of medicine and wealth were shown to be mere foothills and swamps of ignorance in comparison to the new knowledge won by scientific and medical pioneers. Fast forward another hundred years, to our present age, and 1900 now seems like a dim echo of a pastoral past, a quaint era of ignorance, crude medicine, lives cut short by untreatable age-related disease, and earnest poverty - all captured for posterity in fading black and white photographs.

Yet even with all this layered history of progress to look back on, there are a great many people who think that the results of our present medical technology represent an apex of sorts. They think we stand at the top, or somewhere near it, here and now. You don't have to go far to find folk who believe that the healthy human life span will not be greatly increased any time soon, for example. To my eyes, that is a point of view that just hasn't been thought through.

These things have to be looked at in context. This is a roaring age of progress, and each new generation stands that much higher upon the spire we are building.

From ScienceDaily: researchers "have found that the level of a single protein in the tiny roundworm C. elegans determines how long it lives. Worms born without this protein, called arrestin, lived about one-third longer than normal, while worms that had triple the amount of arrestin lived one-third less. ... arrestin interacts with several other proteins within cells to regulate longevity. The human version of one of these proteins is PTEN, a well-known tumor suppressor. ... The links we have found in worms suggest the same kind of interactions occur in mammals although human biology is certainly more complicated. We have much work to do to sort out these pathways, but that is our goal. ... We don't know at this point if human arrestins regulate PTEN function or if anything happens to arrestin levels during the development of cancer. Do increasing levels turn off more PTEN, thus promoting cancer, or do levels decrease and allow PTEN to be more active? ... If it turns out to be the first scenario - that increasing amounts of arrestin turn off the tumor suppressor activity of PTEN, then it may be possible to selectively inhibit that process. We have some interesting work ahead."

Link: http://www.sciencedaily.com/releases/2010/05/100507161423.htm

From EurekAlert!: "Human adult stem cells injected around the damage caused by a heart attack survived in the heart and improved its pumping efficiency for a year in a mouse model ... Injection of a patient's own adult stem cells into the heart has shown some efficacy in assisting recovery after a heart attack in early human clinical trials, [but] nobody knows how they work, or how long the stem cells last and function in the heart. This study shows how one type of adult stem cell works. ... The team's research focused on adult stem cells – those that can differentiate into a limited variety of tissues – that circulate in the blood and are distinguished by the presence of the CD34 protein on the cell surface. ... CD34+ cells are capable of becoming heart muscle cells, called cardiomyocytes, blood vessel cells and smooth muscle cells. ... The CD34+ cells survived in the left ventricle of the heart for 12 months or longer. Left ventricular ejection fraction - a measure of how much blood is pumped from the heart to other organs at each contraction - improved in treated mice compared with controls for 52 weeks. ... This improvement was the result of increased blood vessel formation in and around the injured area, or paracrine signaling by the stem cells to other nearby cells, rather than formation of new heart muscle."

Link: http://www.eurekalert.org/pub_releases/2010-05/uotm-tas050710.php

If you've ever wanted to work with Aubrey de Grey on advancing the Strategies for Engineered Negligible Senescence, here is your chance. The SENS Foundation is looking for someone to fill the position of Academic Coordinator:

SENS Foundation seeks a consultant to act as Academic Coordinator. The Academic Coordinator will be the head of the entire Academic Initiative and be responsible for designing and implementing short, medium, and long term operational strategies which align with the broader aims of SENS Foundation. ... Major projects already in development include the creation of online undergraduate courses in longevity science, development of a comprehensive training program for SENSFAI, continuance and expansion of the scholarship program, formation of a collaboration as a granting entity within a major university system, and implementation of a comprehensive marketing strategy to expand and promote the AI.

...

We are hoping to fill this role immediately. SENS Foundation will provide a support stipend for an approved candidate. To apply, please complete the Academic and Operational Support application form.

The prior coordinator is heading off to work on a cancer immunotherapy startup in the Bay Area. A great many people who volunteered with the Methuselah Foundation and SENS Foundation in past years have gone on to similar work with other organizations. Livly, for example, is another part of that ecosystem, and you'll find a former volunteer highly placed in Genescient. Networking is everything.

A number of past studies have shown improvement in Parkinson's disease with stem cell transplants. Here is another: "Endometrial stem cells injected into the brains of mice with a laboratory-induced form of Parkinson's disease appeared to take over the functioning of brain cells eradicated by the disease. The finding raises the possibility that women with Parkinson's disease could serve as their own stem cell donors. Similarly, because endometrial stem cells are readily available and easy to collect, banks of endometrial stem cells could be stored for men and women with Parkinson's disease. ... In the current study, the researchers generated stem cells using endometrial tissue obtained from nine women who did not have Parkinson's disease and verified that, in laboratory cultures, the unspecialized endometrial stem cells could be transformed into dopamine-producing nerve cells like those in the brain. The researchers also demonstrated that, when injected directly into the brains of mice with a Parkinson's-like condition, endometrial stem cells would develop into dopamine-producing cells. ... stem cells derived from endometrial tissue appear to be less likely to be rejected than are stem cells from other sources."

Link: http://www.sciencedaily.com/releases/2010/05/100506141608.htm

From the New Scientist: "when young mice are learning, a molecular fragment known as an acetyl group binds to a particular point on the histone protein that DNA wraps itself around - with the result that the cluster of learning and memory genes on the surrounding DNA ends up close to the acetyl group. ... This acetyl "cap" was missing in the older mice that had been set the same tasks. From this, the team concludes that the cap acts as an "on" switch for the cluster of learning and memory genes: removing the cap switches off the genes. Next, by injecting an enzyme known to encourage caps to bind to any kind of histone molecule, [researchers] artificially flipped the switch to the on position in old mice. The acetyl group returned to the histone molecule and the mice's learning and memory performance became similar to that of 3-month-old mice. ... it is still not clear why the switch flips off as we get older. One possibility is that it might help us cope with other cellular assaults that come with ageing, such as oxidative stress, [which] would mean that switching it on might have damaging side effects."

Link: http://www.newscientist.com/article/dn18870-gene-switch-rejuvenates-failing-mouse-brains.html

Biomedical gerontologist and engineered longevity advocate Aubrey de Grey is one of the speakers at the Lift10 conference presently taking place in Geneva. You can browse the conference site, watch video of de Grey's presentation at the conference from the channel at Livestream, or take a look at this article from the local press:

Aubrey de Grey declares an end to generations:

"There won’t be generations anymore," says Aubrey de Grey of tomorrow's world where anti-aging treatments will give us at least 30 extra years of life. You’ll be able to keep up with your granddaughter on the ski slopes, he told his host at the Lift 2010 conference in Geneva Thursday 6 May. And for de Grey, the future is close: we can expect to see such treatments within our lifetimes, he believes.

...

The questions people invariably ask de Gray focus on such mundane matters as where all these extra people will live, how pension plans will pay for them and what they’ll do with their time, but he says the questions are not the right ones. We should balance out these against the problems caused right now by "100,000 people a day getting very sick and staying that way a long time and then dying."

No present aspect of our societies can possibly justify the vast toll of death and suffering caused by aging - not to mention the attendant financial burden, which is gargantuan and beyond easy comprehension. Every change in the social order brought about by incremental lengthening of healthy lives should be welcomed as a sign of progress on the road to the defeat of aging.

An interesting example of how immune therapies can eliminate or reduce some of the ways in which the aging body damages itself: "Cholesterol is transported in the blood in LDL particles, which are a kind of fat drops that can accumulate in the walls of blood vessels. LDL activates the immune defence and triggers an inflammation in the blood vessels that leads to atherosclerosis (also known as arteriosclerosis). When the atherosclerotic plaque finally ruptures, a blood clot is formed that in turn can cause a heart attack or stroke. It was previously thought that the inflammation in the blood vessels arises when the T cells react to oxidised LDL particles located in the atherosclerotic plaque. Now, however, [researchers have found] that the opposite is true, namely that the T cells react to components in the normal LDL particles, and that they no longer recognise LDL once it has been oxidised. ... Since reactions to LDL can be dangerous, T cells are normally held in check by inhibitory signals. The body's own control works well as long as the LDL keeps to the blood, liver and lymph glands. But when it accumulates in the artery wall, this inhibition is no longer enough, the T cells are activated and an inflammation arises. ... Vaccination against the receptor that the T cells use to recognise LDL can block the immune reaction and reduce the disease by between 60 and 70 per cent."

Link: http://www.eurekalert.org/pub_releases/2010-05/ki-nav050610.php

Viruses can be used as a form of targeted anti-cancer therapy, and human trials are soon set to start: "Particular parvoviruses normally infect rodents, but they are also infectious for human cells. However, they do not cause any disease symptoms in humans. Most importantly, these viruses have an astonishing property: They kill infected tumors cells without causing any damage to healthy tissue. ... Many different viruses have been tested before in cancer therapy, particularly for treating those types of cancer for which there are no effective established treatment methods. The [researchers] realized early on that parvovirus H-1 has important advantages over other viruses. Now they have been the first to prove that malignant glioblastomas regress completely as a result of treatment with these viruses. ... Parvoviruses pass the blood brain barrier so that they can be administered via the blood stream. In addition, they reproduce in cancer cells, which is particularly important for successful treatment of glioblastoma with its diffuse growth. Thus, the second generation viruses reach and eliminate even those cancer cells that have already settled at some distance from the primary tumor. ... researchers [expect] to be able to admit the first patients to the trial by the end of the year."

Link: http://www.sciencedaily.com/releases/2010/05/100504095106.htm

Excess visceral fat tissue and other side-effects of the sort of high-calorie, low-exercise lifestyle required to pack on the fat will do you great harm in the long term. Getting fat is a choice is for the vast majority of people, a choice made again and again day after day by deciding to eat more calories and skip exercise in favor of other activities. For 99.9% of the audience here: you're not special, and there's nothing in your genes that's making it noticeably easier to gain weight or harder to lose it. But if you let yourself become fat, just as so many other people are doing in this age of comparative wealth and low-cost calories, then it will come back to bite you.

See this paper, for example:

In the second half of the 20th century it became obvious that a relentless increase in diabetes type 2 (DM) affecting the economically affluent countries, is gradually afflicting also the developing world. This review juxtaposes the threat that the DM epidemic represents to mankind, with the astonishing recent discoveries on the role of obesity and of the body fat in this metabolic disorder.

Presently, the highest prevalence of DM is in Saudi Arabia, a country deep in riches generated by its oil wells. DM is very high, in over 10% of adults in the USA, Switzerland and Austria. Prevalence is low in Norway, China and in Iceland. Predictions of epidemiologists for the first third of the 21st century claim up to 2.5 times increase in DM in the Middle East, Sub-Saharan Africa, India, rest of Asia and in the Latin America. In China the number of patients with DM will double but in the economically advanced countries that experienced rise in DM in the 20th century, the increase will be only about 50%. Remarkably, a lowest increase in DM is expected in the countries that formerly belonged to the Soviet political space.

Increasing urbanization, aging populations, obesity, and falling levels of physical activity are all contributing to the rise of DM worldwide. The main cause of DM pandemic is growing prevalence of obesity, in Europe and in the Latin America. In the North America obesity is considered to be responsible for 90% of DM in females. Male obesity is associated with DM slightly less, at 70-80% in the European Union and in the US.

Thin, healthy people aren't thin and healthy because they have magic genes. They're thin and healthy because they are eating less and exercising more than the fat folk. This isn't rocket science, and it does have an impact on the bottom line of your life expectancy.

Ginter E, & Simko V (2010). Diabetes type 2 pandemic in 21st century. Bratislavske lekarske listy, 111 (3), 134-7 PMID: 20437822

From EurekAlert!: "The muscles of elderly people and of people with type 2 diabetes contain lower concentrations of a protein known as PARL (short for 'presenilin-associated rhomboid-like'). PARL plays an important role within cells in remodeling power-generating mitochondria. It's PARL's job to oversee mitochondria's quality control, specifically by maintaining their integrity as the cellular components undergo normal processes of fission and fusion. The findings provide yet another link between insulin resistance and the function of mitochondria. ... When mitochondria aren't functioning properly, food doesn't get metabolized to the level that it should ... Instead of getting burned, fats accumulate in cells where they impair insulin's action. As mitochondria fail to work efficiently, they also produce more damaging free radicals. ... Relative to younger people, older people showed signs of insulin resistance. They also had fewer numbers of mitochondria and lower expression of the PARL gene. ... We hypothesize that impaired PARL function is an important risk factor for the development of insulin resistance in skeletal muscle by decreasing mitochondrial mass and energetics and increasing oxidative stress, thus contributing to impaired glucose metabolism. As insulin resistance continues to develop, mitochondrial function, oxidative damage, and PARL activity may decline further, leading to a vicious cycle that eventually contributes to the development of [diabetes] or other age-associated diseases, including sarcopenia."

Link: http://www.eurekalert.org/pub_releases/2010-05/cp-nci042810.php

The Seattle Times notes recent research: "A new study finds that calorie restriction may bolster the immune system in adults. Researchers [randomly] placed 46 overweight, but not obese, men and women age 20 to 40 on one of two diets for six months: one in which calories were reduced 10 percent, and another in which they were reduced 30 percent. All food was supplied to the test subjects. The participants were tested to see what effect calorie restriction had on their immune system. They were given a delayed-type hypersensitivity test, which can detect allergens, among other things, and is considered a way to check whole-body immune response. Researchers also checked T-cells, a kind of white blood cell, and another immune system marker. At the end of the six months, [delayed type hypersensitivity] response went up in both the 10 percent and the 30 percent calorie-restricted groups compared with the beginning of the study. Both groups also showed improvement in T-cell function."

Link: http://seattletimes.nwsource.com/html/living/2011767490_calories03.html

Regular exercise makes everything better: it's one of the only presently widely available strategies backed by a weight of evidence to show that it slows the biochemical changes of aging in humans. The other being calorie restriction, of course. Here are a couple of articles on the interaction of exercise and the common neurodegenerative condition of Alzheimer's disease:

How Exercise Might Help Keep Alzheimer's At Bay

"The benefits [of exercise] tend to be on the order of a 20 to 30 percent reduction in being diagnosed with Alzheimer's disease and other such diseases," Kramer said. "And again, this isn't universal but this is found in an increasing number of studies."

Kramer said researchers also tend to consider studies that show what exercise does for animals.

"There are improvements in the chemistry of the brain in terms of the molecules that protect the brain, increases in the number of connections between neurons, which allows us to encode new learning and memory, and even the birth of new neurons in one region of the brain that supports memory," he said.

Australian study to reduce Alzheimer’s symptoms through exercise

This study follows on from previously published work by the research team which revealed that walking for two and a half hours per week for 24 weeks significantly improved memory and thinking ability in Australians who were 50 years and older and who reported problems with their memory.

Associate Professor Gerard Byrne, Head of Psychiatry at The University of Queensland and Director of the Older Persons Mental Health Service at the Royal Brisbane & Women's Hospital said: "It is becoming increasingly evident that regular physical exercise is not only important for physical health, but may also be an important part of maintaining a person's memory and thinking ability."

...

The main hypothesis of this study is that participants with mild to moderate Alzheimer's Disease who participate in the personalised training program for 24 weeks will experience significantly less difficulty with their memory and thinking ability by the end of the program than participants who undertook their usual exercise activity.

Bear in mind that in terms of its progression, risk factors, and even some of its biochemistry, Alzheimer's looks a lot like type 2 diabetes. If you are sedentary and fat, you are more likely to suffer from Alzheimer's disease. Notice that exercise doesn't just protect to some degree from degeneration, but if taken up in later life, it can also to some limited extent reverse current degeneration.

This is all far less than what we know to be possible in the future of medical science. But if you keep yourself fit, you stand a greater chance of living to see that future in good enough shape to benefit from it.

From the SENS Foundation: "Progress toward the goal of tissue rejuvenation via stem cells and tissue engineering ("RepleniSENS") is badly hampered by the surprising fragility of human embryonic stem cells (hESC) relative to mouse ESC (mESC). Unlike their murine counterparts, hESC undergo extensive cell death following enzymatic single-cell dissociation; as a result, researchers are forced to rely on laborious mechanical microdissection, or on narrowly-control enzymatic dissociation that ensures that hESC remain above a minimum cluster size. These requirements make their expansion extremely tedious and inefficient. The reasons for the intolerance of hESC to full dissociation - and the development of means to ameliorate it - are therefore of considerable biomedical as well as scientific interest. This month, researchers [report] that they have at once apparently provided the detailed molecular basis for this frustrating anomaly, and its abrogation using either modified culture protocols or either of two small molecules. ... Injected into an area that already enjoys a high level of government and industry investment, these tools bring us closer to realizing the promise of cell therapies and tissue engineering for the treatment of a range of age-related and traumatic diseases and disorders, as well as for the rejuvenation of aging tissues."

Link: http://www.sens.org/node/763

Accelerating Future notes an example of Alcor's work in cryonics provision. We only tend to hear about the times when unusual obstructions crop up, and so it's worth a reminder that Alcor's staff and volunteers regularly make the difficult organization of a cryosuspension look routine: "This past month, Alcor was faced with three members who were admitted to hospice with end-stage conditions. On back-to-back days, two of our members were cryopreserved while the third member's condition has temporarily improved. Through careful planning, we were able to have two members admitted into the same Hospice of the Valley facility, literally across the hall from each other. This allowed Alcor's Arizona team to carefully monitor both members' conditions simultaneously, 24 hours a day. Having three team members and Alcor's Rescue Vehicle on site, we were able to provide immediate stabilization and cool down procedures and exceptionally quick transfer from time of pronouncement to Alcor's surgery suite in 40 minutes and 32 minutes, respectively. These cases were very important as they tested numerous benchmarks of Alcor's abilities ... The real benefit of all of our preparations, training and planning is to our members, who reportedly received excellent perfusions."

Link: http://www.acceleratingfuture.com/michael/blog/2010/05/alcors-93rd-and-94th-patients-cryopreserved-back-to-back/

The Immortality Institute volunteers are making a go of becoming an organization that regularly raises a modest level of funding for scientific research into engineered longevity. You might recall that the first project funded this way was an investigation into the use of pulsed lasers to destroy lipofuscin. This chemical gunk builds up in long-lived cell populations and contributes to age-related damage and dysfunction by harming the garbage collection functions of the lysosomes in our cells. Safely destroying this lipofuscin in one way or another will assist in restoring these garbage collection functions to a youthful level in the cells of elderly, and so is an important facet of any scientific path to actual rejuvenation.

The Institute is presently soliciting project outlines from interested researchers:

Alongside other initiatives, ImmInst aims to fund one or more research projects this year. Such a project should aim to make an original contribution to the field of life extension science or technology.

Ideal projects will:

• have the capacity to deliver advances to the state of the art, or to establish a proof of concept in a promising area in life extension science or technology
• be basic or applied research but basic research should have potential for applied development
• present short updates for Members with interim data, photos from the facility etc at agreed intervals
• be led or overseen by a person with a postgraduate qualification in the relevant field or by a person with demonstrable equivalent experience
• have clearly defined interim milestones
• have a flexible project structure that can be adjusted according to the amount of money raised
• be small in scale - one or two key workers
• be short in duration - 6 months maximum
• not be confidential. ImmInst will expect open and public presentation and discussion of research results but confidentiality will be accepted where a manuscript is prepared for publication.

ImmInst will be able to support a project with a minimum of $2000 and up to $8000, subject to matching by other donors. ImmInst will launch a call for matching donations and every donation generated in that call will go towards the project budget. A total budget of ~$10,000 is an achievable target, more for projects that capture the imagination of the life extension community.

This is a good step forward for the Institute, I think, and creating a funding organization for longevity science is a worthy goal for any of the present generation of advocates and supporters.

From the SENS Foundation: "To date, the dominant therapeutic strategy for both specific age-related diseases and (to the extent that it has been contemplated) the degenerative biological aging process itself, has been based on altering metabolic pathways. Biomedical research has centered on the detailed understanding of pathways seen to be contributing to disease etiology or pathogenesis, and the identification of putatively dysfunctional components hormones, receptors, enzymes, cytokines, etc), which are then targeted for manipulation by small molecules or other means in hopes of normalizing function and thereby alleviating symptoms or slowing progression of pathology. ... there is a critical flaw in the unconsciously-drawn analogy between its use in the development of therapies to manage specific diseases, and its potential for the treatment of the degenerative aging process. Unlike most non-communicative diseases, degenerative aging is not the result of the dysfunction of metabolic pathways, but of the the undesirable long-term side-effects of their normative biochemistry. Put another way: biological aging is the pathological result of perfectly-functioning, [healthy] metabolic processes. ... Thus, transposing the conventional drug-development pathway onto the aging process necessarily entails interfering with the normal metabolism - and doing on an indefinite basis, from the day that a 'patient' first begins therapy until his or her death. But of course, those same pathways evolved to ensure survival and fitness, and their existence and the normal mode of regulation are the very basis of ordinary health and function. We interfere with the intrinsic operation of such pathways at our peril."

Link: http://www.sens.org/node/747

A detailed examination of recent progress from the SENS Foundation: "Recent years have seen both substantial progress, and significant frustration, in the preferred regenerative engineering approach to the treatment and prevention of Alzheimer's disease (AD), and the eventual regeneration of genuinely youthful cognitive function: immunotherapeutic clearance of beta-amyloid (AmyloSENS). ... results appear to many to commend an earlier window of opportunity for intervention, before concomitant [damage] and neuronal losses have made the removal of beta-amyloid alone insufficient for cognitive rescue. Early intervention might also maximize the therapeutic window for vaccination, preventing the burden of beta-amyloid neuropathology from ever reaching levels so high as to interact with other forms of aging damage in already frail and immunosenescent people." Present work on immune therapies for clearing unwanted biochemical junk from the body looks promising - there is every sign that today's advances will broaden into a general technology platform for this purpose. Researchers will be able to develop therapies that can be applied incrementally throughout life to remove the age-related gunk like beta-amyloid before it rises to dangerous levels.

Link: http://www.sens.org/node/757