Armed with newer, cheaper, and better biotechnologies, researchers can measure ever more of the detailed effects of good health practices such as regular exercise, calorie restriction, and the like. It is possible now to examine the workings of metabolism in any specific part of the body in very great detail, all the way down to the molecular machinery in our cells, see how it changes with age, and see how those changes differ with different lifestyle choices. Or at least this can be done in mice - in humans, more statistical work is required to use today's technology to pull apart the differences between young and old, exercising and sedentary. The option to wait around for sizable portions of a human life span isn't there, after all; science moves faster than that.

Here is an open access paper that measures a little more of the effects of exercise, and along the way provides yet another compelling argument to be someone who exercises rather than someone who sits around growing ever more unfit with each passing year:

Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age [also] counters several well-established glial markers of brain aging. Similarly, we show that age-related changes in neurovascular morphology and function were reduced with exercise.

...

Thus, our results show that exercise can potentially mitigate progressive age-related changes in several key non-neuronal elements of the brain. Further, we show that these brain processes are still highly responsive to exercise in the midlife age range, consistent with studies showing that cognitive function can benefit from exercise even if initiated at later ages.

It's never to late to start on exercise. In the future, there will be rejuvenation biotechnologies capable of restoring the old to youthful health and vigor by repairing the low-level biological damage that causes aging. This will happen, I assure you - and it will be one of the least of the amazing new things to arrive in the years ahead. But human rejuvenation will almost certainly arrive later that either you or I desire, and until such time as it does become widely available the best things you can do for your own personal future of health and longevity are pretty primitive - lifestyle choices and supporting research and development.

All told, the better you do with the cards you have now, the more likely you are to live to benefit from the future of longevity-enhancing medicine. So do better.

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

Via EurekAlert!: researchers "created super strong, marathon mice and nematodes by reducing the function of a natural inhibitor, suggesting treatments for age-related or genetically caused muscle degeneration are within reach. It turns out that a tiny inhibitor may be responsible for how strong and powerful our muscles can be. ... By acting on a receptor (NCoR1), [researchers] were able to modulate the transcription of certain genes, creating a strain of mighty mice whose muscles were twice a strong as those of normal mice. ... By genetically manipulating the offspring of [mice and nematodes], the researchers were able to suppress the NCoR1 corepressor, which normally acts to inhibit the buildup of muscle tissues. ... In the absence of the inhibitor, the muscle tissue developed much more effectively. The mice with the mutation became true marathoners, capable of running faster and longer before showing any signs of fatigue. In fact, they were able to cover almost twice the distance run by mice that hadn't received the treatment. They also exhibited better cold tolerance. Unlike previous experiments with so-called super mice, this study addresses the way energy is burned in the muscle and the way the muscle is built. Examination under a microscope confirmed that the muscle fibers of the modified mice are denser, the muscles are more massive, and the cells in the tissue contain higher numbers of mitochondria - cellular organelles that deliver energy to the muscles. Similar results were also observed in nematode worms, allowing the scientists to conclude that their results could be applicable to a large range of living creatures."

Link: http://www.eurekalert.org/pub_releases/2011-11/epfd-tag110711.php

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

Michael Rae is the co-author of Ending Aging, a research assistant at the SENS Foundation, and a long-standing figure of note in the calorie restriction community: "I would say that one exciting recent development is that, with an increase in our research budget this year (based on performance last year and a more optimistic financial outlook from many of our donors), we've recently approved funding for several quite important and exciting research projects. One is a project whose ultimate aim is to tissue engineer a new thymus. The thymus is a gland located near the breast bone, where T-cells (an important immune cell) mature. The thymus shrinks with age, and the tissues on the outer layer of the organ where T-cells mature lose their architectural integrity, leading to a progressive failure to produce new T-cells to fight novel infections. The thymus engineering project, which is underway with SENS Foundation support at the Wake Forest University Institute for Regenerative Medicine by Dr. John Jackson and colleagues, is to use a trick that you may have heard of having been used to make a new rat heart using the tissue scaffolding of another's. ... The fifth SENS Conference was, indeed, quite amazing! Unlike the previous conference, this time much more of the work being presented had already been published; it was none the less remarkable to see just how much had been accomplished in the last year, from restoring cognitive function in a mouse model of Alzheimer's disease using a drug that boosted up the ability of their brains' lysosomes ('garbage disposal systems' as it were) to break down the sticky beta-amyloid protein [to] a just-begun study on a very bold and ambitious way [to] restore the loss of cells and degraded circuitry of the aging neocortex (the area of the brain where, arguably, our highest, most 'human' cognitive activity occurs)."

Link: http://www.digitaljournal.com/article/314216

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

Naked mole rats are of interest to researchers because they can live nine times as long as comparable rodent species: this implies that they are a good place to look for determinants of longevity and important mechanisms of aging. You can go far in biology by comparing similar species that nonetheless exhibit sharply defined differences in your area of interest. The naked mole rat genome was sequenced and published this year, but research into the genetics of aging in the species that predates the availability of the full genome is still arriving at the presses. For example, there is this open access paper:

RNA Sequencing Reveals Differential Expression of Mitochondrial and Oxidation Reduction Genes in the Long-Lived Naked Mole-Rat When Compared to Mice

The naked mole-rat is not only the longest-lived rodent, but has a much longer lifespan than expected for its relatively small body size and has been shown to be extremely resistant to neoplasia. Furthermore, since a number of other rodents including mice, rats and guinea pigs already have had their genome sequenced, the naked mole-rat is a prime candidate for comparative genomics studies. ... Using a combination of 2nd-generation sequencing platforms, [we] were able to compare gene expression between wild-derived mice and naked mole-rats without using a naked mole-rat reference genome.

Gene expression is the process by which proteins are produced from the DNA blueprint. How much of any given protein is produced at any given time, and how that changes over time and in response to circumstances, is at least as important as what the protein is. Examining different levels of protein production between neighboring species is a good way to narrow down the biological mechanisms that explain their differences. In this case:

Within over-expressed genes in the naked mole-rat, genes associated with oxidoreduction were strongly overrepresented as well as genes associated with mitochondria and more specifically mitochondrial matrix. Consistent with the free radical theory of ageing, the over-expression of genes related to oxidoreduction could protect the naked mole-rat from reactive oxygen species. [With caveats, and] in view of the hypothesis that mitochondria play a major role in mammalian ageing, these results point towards a putative role for oxidoreduction and mitochondrial alterations in the long lifespan of the naked mole-rat.

You might compare this view with the membrane pacemaker hypothesis, that has naked mole rat longevity stemming from the fact that vulnerable cell components such as mitochondria are have a composition that renders them resistant to damage caused by free radicals, the reactive byproducts of cellular-fuel-generation taking place within mitochondria. The mitochondria themselves are the first target for those free radicals, and if you look back in the Fight Aging! archives, you'll find an explanation as to how damage to mitochondria can spiral into damage throughout the body - and hence aging.

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

A good demonstration of the state of the art of tissue engineering: "Last spring, a research team at Japan's RIKEN Center for Developmental Biology created retina-like structures from cultured mouse embryonic stem cells. This week, the same group reports that it's achieved an even more complicated feat - synthesizing a stem-cell-derived pituitary gland. The pituitary gland is a small organ at the base of the brain that produces many important hormones and is a key part of the body's endocrine system. It's especially crucial during early development, so the ability to simulate its formation in the lab could help researchers better understand how these developmental processes work. ... The experiment wouldn't have been possible without a three-dimensional cell culture. The pituitary gland is an independent organ, but it can't develop without chemical signals from the hypothalamus, the brain region that sits just above it. With a three-dimensional culture, the researchers could grow both types of tissue together, allowing the stem cells to self-assemble into a mouse pituitary. ... Using this method, we could mimic the early mouse development more smoothly, since the embryo develops in 3-D in vivo. ... Fluorescence staining showed that the cultured pituitary tissue expressed the appropriate biomarkers and secreted the right hormones. The researchers went a step further and tested the functionality of their synthesized organs by transplanting them into mice with pituitary deficits. The transplants were a success, restoring levels of glucocorticoid hormones in the blood and reversing behavioral symptoms, such as lethargy."

Link: http://www.technologyreview.com/biomedicine/39108/

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

Tengion is one of the research groups attempting to tissue engineer replacement sections of intestine: "Tengion has demonstrated that smooth muscle cells seeded on its biological scaffolding and then implanted in rodents exhibit functional regeneration of both the inner lining of epithelial cells and the surrounding layers of small intestine smooth muscle cells in as little as eight weeks post-implantation. ... The regeneration of small intestine from smooth muscle cells using our technology platform represents an important step forward in the development of functional, regenerated organs. Our goal is to translate preclinical data and proof of concept findings into clinical programs that could represent a broad range of medical treatment possibilities for patients in need of new bladders, kidneys and other organs. ... In this preclinical study, patch and tubular constructs were implanted in rodent small intestines and histologically evaluated for evidence of regeneration of the neo-mucosa and muscle layers. In as little as eight weeks post-implantation, laminarly organized neo-mucosa and muscle layer bundles were demonstrated, supporting the approach of using autologous smooth muscle cells and biomaterial combination products to spur regeneration of the small intestine. Patients with short bowel syndrome have typically undergone extensive small intestine resectioning and may become dependent on parenteral nutrition, a costly treatment associated with multiple complications, and could potentially benefit from a regenerative medicine approach."

Link: http://www.marketwatch.com/story/tengion-organ-regeneration-platform-technology-demonstrates-ability-to-regenerate-small-intestine-in-preclinical-models-data-published-in-regenerative-medicine-2011-11-07

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

The best communities involved in advocacy and outreach are balanced somewhere between eagerness ("It's all so obvious, look what we could achieve!") and frustration ("But it's all so obvious - why don't they get it?"). Advocacy is hard despite its simplicity and time-worn, well-understood nature: it is hard because it is slow and incremental toil at the best of times, the human relations equivalent of banging two rocks together to make fire. You talk to people, you persuade people to your way of looking at things over and over and over again, making tiny little gains each time. For longevity science, the people willing to do this work are generally the bright sparks, the early adopters and foresightful folk who see the opportunity to defeat aging, see how plausible it is, and are full of enthusiasm for this goal. They are then run into the meatgrinder of tiny, incremental progress in persuading the world one person at a time.

Occasionally this isn't pretty, and hence the frustration. None of us are getting any younger, and while the science is so very obviously heading the right direction to produce working rejuvenation biotechnology, it is doing so very, very slowly. Only a minuscule fraction of the scientific community are working on relevant projects, there is next to no funding, and only a minuscule fraction of the public at large care one way or another. That needs to change, and changing it is slow going.

Here's some frustration from the Russian side of the community, translated, and further smoothed out by my edits:

It's aging that kills people. Also it's stupidity and greed that kill people. It exactly the stupidity and greed that prevents people from doing much to survive. The society spends an abysmally small amount of effort on life extension. Minimal interest and microscopic funding goes to studying of fundamental mechanisms of aging. Resources are being spent on any any old thing, but not on longevity. Years go by, and people become dung and rot in their graves. Because of their own stupidity and imbecility of others.

Almost everyone who comes to somebody's funeral should keep saying: "We are the sick people, we killed you by our passivity. Moreover, we keep on bringing death further on. The thought to identify the underlying reasons of death and to try to eliminate them doesn't even sneak into our empty minds. It's actually only money and pleasure that matter to us, and in indulging that we seek our own death."

I would have written "ignorance" in place of "stupidity," but Russian has a somewhat different set of overlapping meanings for words involving lack of knowledge, poor application of knowledge, and lack of intelligence. "Foolishness" or "unreasonableness" is as good a translation as "stupidity" from the original, I think. To my eyes people are rarely forthrightly stupid, but the small slice of attention that a person gives to matters outside his focus looks stupid from a distance - and most people give next to no attention to longevity science. That is foolish in this day and age, as it amounts to remaining blind to a tremendous opportunity just because you didn't take a small amount of time and effort to check on it.

There is a brass ring to be grasped: as someone who has spent a fair amount of time following the science and biotechnology, I can say with some conviction that it is clearly possible for us to engineer our way to agelessness in stages within a few decades from where we stand today. To do that, however, will require radical success in advocacy, fundraising, and growing the longevity science community over the next ten years.

Thus frustration stems from the size of the opportunity, the sheer obviousness of the imperative to defeat aging once you grasp it, and the feeling that the opportunity to achieve this goal in our lifetimes might be slipping from our grasp despite our progress to date. That's what things look like in the early stages of an exponential growth curve; it seems as though you'll never get there in time, but it takes off late in the game. Unfortunately it's also what things look like in the early stages of linear growth that will remain small - see the cryonics community, for example. We can't tell how the future will turn out, but we have to keep coming back to work at building it: the way to ensure the next few decades go badly for longevity science is to fail to try to do better.

You can't blame the rest of the world for not listening if you're not talking to them in the right way.

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

A good example of the next generation of targeted cancer therapies is outlined at the Technology Review: "scientists at the National Cancer Institute have developed a possible solution that involves pairing cancer-specific antibodies with a heat-sensitive fluorescent dye. The dye is nontoxic on its own, but when it comes into contact with near-infrared light, it heats up and essentially burns a small hole in the cell membrane it has attached to, killing the cell. To target the tumor cells, the researchers used antibodies that bind to proteins that are overexpressed in cancer cells. ... Normal cells may have a hundred copies of these antibodies, but cancer cells have millions of copies. That's a big difference. ... The result is that only cancer cells are vulnerable to the light-activated cascade. ... The researchers tested the new treatment in mice and found that it reduced tumor growth and prolonged survival. There are a few kinks to work out before the system can be adapted for humans, though. For instance, the researchers couldn't test the treatment's effect on large tumors, since killing off too many cells at once caused cardiovascular problems in the mice. Finding the right cancer-cell markers to pair with the dye may also prove difficult. For example, HER-2, one of the proteins targeted in the study, is only expressed in 40 percent of breast-cancer cells in humans. Still, the lack of toxicity associated with the treatment is a huge advantage,"

Link: http://www.technologyreview.com/biomedicine/39082/

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

A human interest piece on research into the genetics and biochemistry of centenarians amongst the Ashkenazi Jewish population: "Irving Kahn is about to celebrate his 106th birthday. He still goes to work every day. Scientists are studying him and several hundred other Ashkenazim to find out what keeps them going. And going. And going. ... The world's oldest stockbroker, he first went to work on Wall Street in 1928. ... Still, a man who at 105 - he'll be 106 on December 19 - has never had a life-threatening disease, who takes no cholesterol or blood-pressure medications and can give himself a clean shave each morning (not to mention a 'serious sponge bath with vigorous rubbing all around'), invites certain questions. Is there something about his habits that predisposed a long and healthy life? (He smoked for years.) Is there something about his attitude? (He thinks maybe.) Is there something about his genes? (He thinks not.) And here he cuts me off. He's not interested in his longevity. But scientists are. ... Pharmaceutical companies and the National Institutes of Health are throwing money into longevity research. Major medical centers have built programs to satisfy the demand for data and, eventually, drugs. Irving himself agreed to have his blood taken and answer questions for the granddaddy of these studies, the Longevity Genes Project at Albert Einstein College of Medicine in the Bronx, which seeks to determine whether people who live healthily into their tenth or eleventh decade have something in common - and if so, whether it can be made available to everyone else."

Link: http://nymag.com/print/?/news/features/ashkenazi-jews-2011-11/

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

The future of your health is a matter of chance and likelihood: you have the power to shape that statistical landscape through good lifestyle choices and strategies such as helping to fund research into rejuvenation biotechnology and signing up with a cryonics provider - but nothing is a certainty. You can shift your chances, shift your life expectancy (itself a statistical measure), but you can't entirely remove happenstance and sheer bad luck. You are far better off by making and following good plans, but bad end results are still possible.

For example, even someone who signs up to be cryopreserved and does a good job of managing the organization of his own cryosuspension at the end of life can still be cut short by bad luck:

Alcor member A-1088, Dennis Ross, was pronounced legally dead on Sunday October 30, 2011. A neurocryopreservation, Mr. Ross became Alcor's 108th patient. Alcor received emergency notification that a member in the St. Petersburg, Florida area had been rushed to the hospital on Friday, October 28th and was diagnosed with a massive intracerebral hemorrhagic stroke due to a ruptured brain aneurysm.

Suspended Animation (SA) went to the hospital and began to prepare for a probable cryonics case. Through medical imaging on October 30, physicians determined the individual's brain damage was so extensive they declared him brain-dead. After the family decided to withdraw life support, SA performed field stabilization and attempted washout; however their success was limited due to the compromised blood flow of the brain. SA completed a neuroseparation before shipping the anatomical donation on dry ice to Alcor.

It's important to recognize that, despite best reasonable efforts, the possibility remains that we are going to be betrayed by our own biology in the end. The quote above is an unfortunate example of the type, in which the patient suffered a brain-damaging end of life incident that will greatly reduce the possibility of a good cryopreservation - and that despite high quality support from medical staff and everyone else involved in organizing the response. You'll recall that the point of cryonics is to preserve the fine structure of the brain, within which is the data that makes up the mind - keep that and none of the other damage matters in the long term. But the more neural damage that occurs prior to cooling, the worse the end result will be.

So the best preparation in the world can be sabotaged by the body breaking down in exactly the wrong way at the end of life. All we can do is strive to minimize the risks. In the case of cryonics, many of these late stage risks exist because Western legal systems make it impossible for people and services to collaborate in order to arrange the time and manner of death. Self-determination in end of life choices, and the ability to help people enact those choices, would make cryopreservation of the old and frail far less expensive and far less subject to risk of neural damage. This is just one of countless injustices and losses of freedom inherent in modern governance and law.

But back to the original point: the best we can do is to work to minimize risk. Risk cannot be removed entirely, and we all live in fragile bodies.

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