An example of ongoing work to make targeted cell-killing technologies economically practical: "For more than a decade, researchers have been trying to develop nanoparticles that would deliver drugs more effectively and safely. The idea is that a nanoparticle containing a drug compound could selectively target tumor cells or otherwise diseased cells, and avoid healthy ones. Antibodies or other molecules can be attached to the nanoparticle and used to precisely identify target cells. ... [Researchers] devised a method by which the building blocks of the nanoparticle and the drug self-assemble into a final product. Two types of polymer combine to form the tangled mesh of [a] drug-laden spherical nanoparticle. One of these polymers has two chemically and structurally distinct regions, or 'blocks': a water-insoluble block that forms part of the mesh that encapsulates the drug, and a water-soluble block that gives the final product a stealthy corona to evade the immune system. The other type of polymer has three blocks: the same two as the first, as well as a third region that contains a targeting molecule - the signal that will ensure the final particles attach to the desired cell types. The drug-carrying nanoparticles are formed by simply mixing these polymers together with the drug in the appropriate conditions. The self-assembling polymers can be produced in a repeatable and scalable fashion. But the method has an additional benefit ... The method by which the nanoparticles are built - from individual preparations of the two-block and three-block polymers - would also let researchers use high-throughput screening approaches, akin to how medicinal chemists design and test new drug compounds. Each block could be tweaked - extend one block, change the charge on another - and the relative amounts of each polymer could be varied. With so many parameters for tinkering, [scientists] can screen many combinations."

Link: http://www.technologyreview.com/biomedicine/40347/

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

Here is another study showing that rapamycin can extend life in mammals: "The nutrient-sensing TOR (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TOR, extends lifespan in yeast, fruit flies and genetically heterogeneous mice. Here, we demonstrate that lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of [two years]. Importantly, rapamycin was administrated intermittently (2 weeks per month) starting from the age of [two months]. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group. Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin. This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22107964

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

The field of stem cell research is busy indeed, as is the application of new knowledge in regenerative medicine. More and more news that would have been noteworthy five years ago just slips past with a brief mention now - so you might imagine what will be buried in the academic press releases by 2016. By that time, examples of unarguably, demonstrably successful human autologous stem cell therapies will be yesterday's news, offered to hundreds or thousands of patients in many clinics outside the US, and you'll have to do better than repair the ravages of disease or injury in a mouse to gain the attention of the press. But for now, the following items are examples of comparatively buried news - the everyday advances in the field that are no longer written up in glowing editorials. Progress is measured by the increasing degree to which your work has faded into the background hum of science under way.

Newly discovered heart stem cells make muscle and bone:

Researchers have identified a new and relatively abundant pool of stem cells in the heart. ... these heart cells have the capacity for long-term expansion and can form a variety of cell types, including muscle, bone, neural and heart cells. ... While cell-based therapies do have potential for repairing damaged heart tissue, [researchers] ultimately favors the notion of regenerative therapies designed to tap into the natural ability of the heart and other organs to repair themselves. And there is more work to do to understand exactly what role these stem cells play in that repair process. [The] team is now exploring some of the factors that bring those cardiac stem cells out of their dormant state in response to injury and protect their "stemness."

Repairing spinal cord injury with dental pulp stem cells:

Hope that a stem cell population, specifically dental pulp stem cells, might be of benefit to individuals with severe spinal cord injury has now been provided by the work of Akihito Yamamoto and colleagues, at Nagoya University Graduate School of Medicine, Japan, in a rat model of this devastating condition. In the study, when rats with severe spinal cord injury were transplanted with human dental pulp stem cells they showed marked recovery of hind limb function. Detailed analysis revealed that the human dental pulp stem cells mediated their effects in three ways: they inhibited the death of nerve cells and their support cells; they promoted the regeneration of severed nerves; and they replaced lost support cells by generating new ones.

UCLA researchers identify new method for generating stem cell-like cells from human skin:

Researchers from the UCLA School of Dentistry investigating how stem cells can be used to regenerate dental tissue have discovered a way to produce cells with stem cell-like characteristics from the most common type of human skin cell in the epidermis. These skin cells, called keratinocytes, form the outermost layer of skin and can be cultured from discarded skin tissues or biopsy specimens. ... Since [these stem cells] may be obtained by taking a small punch-biopsy of skin tissues from patients, these cells are an easily accessible, patient-specific source of stem cells, which can be used for regenerative purposes.

Adult stem cells use special pathways to repair damaged muscle:

When a muscle is damaged, dormant adult stem cells called satellite cells are signaled to "wake up" and contribute to repairing the muscle. University of Missouri researchers recently found how even distant satellite cells could help with the repair, and are now learning how the stem cells travel within the tissue. This knowledge could ultimately help doctors more effectively treat muscle disorders such as muscular dystrophy, in which the muscle is easily damaged and the patient's satellite cells have lost the ability to repair.

And that was just a random selection of stem cell news grabbed from the top of today's pile. It's a busy time for the life sciences, and we will all benefit from the results ten or twenty or thirty years from now.

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

Teaching the immune system to kill cancer is an ongoing concern in laboratories around the world, and the state of the art is pretty effective these days - though in the overregulated world of medicine, a decade or more can separate working methods in the laboratory from working therapies in the clinic, and most of that delay entirely unnecessary. Here is a good example of what is presently possible:

Researchers from UCLA's cancer and stem cell centers have demonstrated for the first time that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma. ... Researchers used a T-cell receptor from a cancer patient cloned by other scientists that seeks out an antigen expressed by this type of melanoma. They then genetically engineered the human blood stem cells by importing genes for the T-cell receptor into the stem cell nucleus using a viral vehicle. The genes integrate with the cell DNA and are permanently incorporated into the blood stem cells, theoretically enabling them to produce melanoma-fighting cells indefinitely and when needed.

...

In the study, the engineered blood stem cells were placed into human thymus tissue that had been implanted in the mice, allowing Zack and his team to study the human immune system reaction to melanoma in a living organism. Over time, about six weeks, the engineered blood stem cells developed into a large population of mature, melanoma-specific T-cells that were able to target the right cancer cells. ... The study included nine mice. In four animals, the antigen-expressing melanomas were completely eliminated. In the other five mice, the antigen-expressing melanomas decreased in size.

I'm not overly worried about the cancers that my body is likely to start generating in two or three decades; they will be a risk, but a small risk, more of a financial inconvenience than a genuinely threatening medical condition. By the 2040s this sort of guided approach to eliminating cancer will have long been a mainstream staple in clinics, a mature technology that will benefit from years of refinement, experience, and incremental improvements - and bear in mind that this is just one of a number of different branches of next generation cancer therapy presently under development and achieving similar results.

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

As a follow up to an earlier post on why DNA sequencing is of interest to those of us who follow longevity science, here is a look at the present state of the sequencing industry: "BGI, based in China, is the world's largest genomics research institute, with 167 DNA sequencers producing the equivalent of 2,000 human genomes a day. BGI churns out so much data that it often cannot transmit its results to clients or collaborators over the Internet or other communications lines because that would take weeks. Instead, it sends computer disks containing the data, via FedEx. ... the ability to determine DNA sequences is starting to outrun the ability of researchers to store, transmit and especially to analyze the data. ... Data handling is now the bottleneck. It costs more to analyze a genome than to sequence a genome. ... That could delay the day when DNA sequencing is routinely used in medicine. In only a year or two, the cost of determining a person's complete DNA blueprint is expected to fall below $1,000. But that long-awaited threshold excludes the cost of making sense of that data, which is becoming a bigger part of the total cost as sequencing costs themselves decline. ... We believe the field of bioinformatics for genetic analysis will be one of the biggest areas of disruptive innovation in life science tools over the next few years."

Link: http://www.nytimes.com/2011/12/01/business/dna-sequencing-caught-in-deluge-of-data.html

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

Mitochondria are the power plants of the cell, the evolved remnants of what were originally symbiotic bacteria, and which still possess their own fragile DNA distinct from that in the cell nucleus. They churn away producing the adenosine_triphosphate (ATP) used as an energy source in cellular processes, and are clearly of great importance in determining longevity. Scientists have for some years been carefully pulling apart the core mitochondrial machinery to better understand why this is the case, and here is an example of this ongoing research: "A decrease in mitochondrial electron transport chain (ETC) activity results in an extended lifespan in Caenorhabditis elegans. This longevity has only been reported when complexes I, III and IV genes are silenced, but not genes of complex II. We now have suppressed each complex II subunit in turn and have confirmed that in no case is lifespan extended. Animals with impaired complex II function exhibit similar metabolic changes to those observed following suppression of complexes I, III and IV genes, but the magnitude of the changes is smaller. Furthermore, an inverse correlation exists between mitochondrial membrane potential and ATP levels, which strongly suggests that dynamic allocation of energy resources is maintained. In contrast, suppression of genes from complexes I, III and IV, results in a metabolic crisis with an associated stress response and loss of metabolic flexibility. Thus, the maintenance of a normal metabolism at a moderately decreased level does not alter normal lifespan, whereas metabolic crisis and induction of a stress response is linked to lifespan extension."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22122855

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

Spurring regeneration of muscle is of interest as as a part of any future rejuvenation biotechnology package because humans and other mammals progressively lose muscle mass and strength with age - aside from the sedentary lifestyle that most older people adopt, there are underlying processes that sap muscle strength even in athletes. Stepping on the gas and telling the body to build new muscle - when it ordinarily would not do so - isn't as good an approach as preventing muscle loss from happening in the first place, or at least attenuating some of the mechanisms involved, but it certainly closer to realization at this point in time.

As a demonstration of that fact, here are researchers building new muscle in mice using one of the many specialist techniques for delivering stem cells that are presently evolving in the laboratory:

Researchers removed a portion of the tibialis anterior leg muscle in several mice (the muscle was chosen because injury to it affects the foot's range of motion but doesn't prevent the mice from walking). In some mice, the injuries were left to heal on their own. In others, the wound was filled with bundles of microthreads seeded with reprogrammed human muscle cells. The untreated mice developed significant scarring at the injury site, with no restoration of muscle function. In sharp contrast, the mice that received the reprogrammed cells grew new muscle fibers and developed very little scarring.

Tests done 10 weeks after implantation showed that the regenerated tibialis anterior muscle functioned with nearly as much strength as an uninjured muscle. The scientists expected that most of the regenerated muscle would be composed of human cells, since the implanted cells were from human muscle. Surprisingly, most of the new muscle fibers were made of mouse cells. The team theorized that the fibrin microthreads, which in their composition and shape are similar to muscle fibers, may encourage resident mouse progenitor cells to migrate into the wound and begin restoring the tissue (they may also forestall the natural inflammatory response that leads to scarring after a major injury).

This surprise finding suggests that fibrin microthreads alone could be used to treat major muscle trauma while research on enhancing regeneration with reprogrammed human cells continues.

Yet another line of research to keep an eye on: the ultimate destination of regenerative medicine is to move away from introducing new cells and towards using signals to tell existing cells to get to work. A lot of these potential signals are being discovered through accident and guided guesswork at the present time, but this will become a more purposeful process of discovery as understanding of the deepest and most complex levels of our biological processes increases.

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

Via EurekAlert!: "One of the earliest known impairments caused by Alzheimer's disease - loss of sense of smell - can be restored by removing a plaque-forming protein in a mouse model of the disease. The study confirms that the protein, called amyloid beta, causes the loss. ... The evidence indicates we can use the sense of smell to determine if someone may get Alzheimer's disease, and use changes in sense of smell to begin treatments, instead of waiting until someone has issues learning and remembering. We can also use smell to see if therapies are working. ... just a tiny amount of amyloid beta - too little to be seen on today's brain scans - causes smell loss in mouse models. Amyloid beta plaque accumulated first in parts of the brain associated with smell, well before accumulating in areas associated with cognition and coordination. Early on, the olfactory bulb, where odor information from the nose is processed, became hyperactive. Over time, however, the level of amyloid beta increased in the olfactory bulb and the bulb became hypoactive. Despite spending more time sniffing, the mice failed to remember smells and became incapable of telling the difference between odors. The same pattern is seen in people with the disease. They become unresponsive to smells as they age. ... The team then sought to reverse the effects. Mice were given a synthetic liver x-receptor agonist, a drug that clears amyloid beta from the brain. After two weeks on the drug, the mice could process smells normally. After withdrawal of the drug for one week, impairments returned."

Link: http://www.eurekalert.org/pub_releases/2011-11/cwru-eso113011.php

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

The use of 3D printers is spreading in medical research and development: "researchers have used a 3D printer to create a bone-like material and structure that can be used in orthopedic procedures, dental work, and to deliver medicine for treating osteoporosis. Paired with actual bone, it acts as a scaffold for new bone to grow on and ultimately dissolves with no apparent ill effects. The authors [say] they're already seeing promising results with in vivo tests on rats and rabbits. It's possible that doctors will be able to custom order replacement bone tissue in a few years ... If a doctor has a CT scan of a defect, we can convert it to a CAD file and make the scaffold according to the defect ... The material grows out of a four-year interdisciplinary effort involving chemistry, materials science, biology and manufacturing. A main finding of the paper is that the addition of silicon and zinc more than doubled the strength of the main material, calcium phosphate. The researchers also spent a year optimizing a commercially available ProMetal 3D printer designed to make metal objects. The printer works by having an inkjet spray a plastic binder over a bed of powder in layers of 20 microns, about half the width of a human hair. Following a computer's directions, it creates a channeled cylinder the size of a pencil eraser. After just a week in a medium with immature human bone cells, the scaffold was supporting a network of new bone cells."

Link: http://medicalxpress.com/news/2011-11-3d-printer-bone-like-material.html

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

Because veterinary medicine is less (oppressively) regulated than human medicine, animals are benefiting from stem cell therapies that are safe enough for human use but nonetheless still illegal to commercially develop in the US: "In a very unusual breakthrough, a stem cell treatment for racehorses is ready to be tried ... on you. British scientists pioneered a technique in horses where an individuals' own stem cells are grown outside the body, then injected into the damaged tendon. There will be a clinical trial in the UK in which 24 human patients will undergo this radical new stem cell treatment for similar tendon injuries. We'll tell you about the proven benefits in racehorses so you'll understand the possible benefits in people. The test subjects who join the clinical trial will be in the unique position of enjoying a medical procedure that is years behind the veterinary equivalent. If human beings have the same barely believable 80% recovery rate, this will be a leap forward for sports medicine. ... The reason animals can get commercial drugs and treatments faster than people in the US and other Western countries is simple: there is enormous oversight in human medical research. Veterinary research is comparably simple. According to the FDA, bringing a new drug to market for humans requires pre-clinical laboratory tests, animal tests, and human clinical trials. Each one of those steps costs money, lots and lots of it. Approval for veterinary drugs is simpler, requiring a single study that proves the drug is safe and effective. Because of regulatory difference, progress on animal medical research can move very quickly compared to human research."

Link: http://singularityhub.com/2011/03/10/uk-stem-cell-company-cures-race-horse-tendons-humans-next/

The present generation of therapies for rheumatoid arthritis are based on TNF inhibition - a fairly crude manipulation of the immune system when considered in the grand scheme of what is possible, but one that is getting better. From Technology Review: "A new protein engineered to inhibit molecules that cause inflammation not only reduces symptoms of rheumatoid arthritis in mice but also may have potential to reverse the disease's course. Researchers hope the findings will point toward a new therapy for this crippling and difficult-to-treat disease, which occurs when the immune system attacks the body's own joints. Even medications that are most successful in halting joint inflammation are effective in only about half of the patients who try them. ... The new synthetic protein [appears] to target TNF in a far more specific fashion and could be produced at a small fraction of the cost [of present TNF inhibitors]. ... a protein called progranulin binds to TNF receptors and that administering the protein to mice with rheumatoid arthritis reduced or even eliminated their symptoms. Then they determined which fragments of progranulin were responsible for binding to TNF and combined those fragments to engineer a protein that works even better to suppress disease. Mice with mild arthritis appeared to be disease-free after several weeks of regular injections of the modified progranulin."

Link: http://technologyreview.com/biomedicine/35091/

To go along with a recent post on cell therapies for nerve regeneration, here researchers investigate a different set of mechanisms: "A protein required to regrow injured peripheral nerves has been identified by researchers. ... The finding, in mice, has implications for improving recovery after nerve injury in the extremities. It also opens new avenues of investigation toward triggering nerve regeneration in the central nervous system, notorious for its inability to heal. ... scientists show that a protein called dual leucine zipper kinase (DLK) regulates signals that tell the nerve cell it has been injured - often communicating over distances of several feet. The protein governs whether the neuron turns on its regeneration program. ... How does an injured nerve know that it is injured? How does it take that information and turn on a regenerative program and regrow connections? And why does only the peripheral nervous system respond this way, while the central nervous system does not? We think DLK is part of the answer. ... If an axon is severed somewhere between the cell body in the spinal cord and the muscle, the piece of axon that is no longer connected to the cell body begins to disintegrate. Earlier work showed that DLK helps regulate this axonal degeneration. And in worms and flies, DLK also is known to govern the formation of an axon's growth cone, the structure responsible for extending the tip of a growing axon whether after injury or during development. The formation of the growth cone is an important part of the early, local response of a nerve to injury. But a later response, traveling over greater distances, proves vital for relaying the signals that activate genes promoting regeneration. This late response can happen hours or even days after injury. But in mice, unlike worms and flies, [DLK] is not involved in an axon's early response to injury. Even without DLK, the growth cone forms. But a lack of DLK means the nerve cell body, nestled in the spinal cord far from the injury, doesn't get the message that it's injured. Without the signals relaying the injury message, the cell body doesn't turn on its regeneration program and the growth cone's progress in extending the axon stalls. ... A neuron that has seen a previous injury now has a different regenerative program than one that has never been damaged. We hope to be able to identify what is different between these two neurons - specifically what factors lead to the improved regeneration after a second injury. We have found that activated DLK is one such factor. We would like to activate DLK in a newly injured neuron to see if it has improved regeneration."

Link: http://www.sciencedaily.com/releases/2012/06/120620132926.htm

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

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."

View the Article Under Discussion: http://www.acceleratingfuture.com/michael/blog/2010/05/alcors-93rd-and-94th-patients-cryopreserved-back-to-back/

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An excellent article from CNBC looks at some of the few figures in the investment community who support progress towards extended healthy lifespans: "what if 'getting old' wasn't really 'getting old?' What if aging - at least the physical deteriorations that accompany it - was something that could be prevented? It's a lofty idea, but it's one that a new breed of biotech start-ups, scientists, and prominent investors are beginning to tackle. Peter Thiel is one of those investors. ... Back in 2006, Thiel gave Cambridge anti-aging researcher Aubrey de Grey $3.5 million under the auspices of the Methusaleh Foundation, a non-profit headquartered in Springfield, Virgina, that awards scientists who are working on life-extension therapies. 'Probably the most extreme form of inequality is between people who are alive and people who are dead,' Thiel told The New Yorker. In 2010, Thiel and his partners at Founders Fund, a Bay Area venture capital firm, invested $500,000 in Halcyon Molecular, a biotech start-up whose 28-year-old founder has a 'dream to create a world free from cancer and aging.' To understand the fund's investment, you have to appreciate what Founders Fund is - or, more specifically, what it is not. 'These are not guys who care about an extra million dollars,' says Brian Singerman, a partner at Founders Fund along with Thiel. 'These are guys who wanted to do something amazing for the world.' Singerman, an early employee at Google, [came] to Founders Fund after having what he describes as an 'epic six hour epic dinner with Sean Parker.' Equal parts brilliant and idealistic, Singerman is adamant that aging is a problem that can be solved. The fund's portfolio has invested in about 14 health and biotech companies all interested in solving life's ultimate problem: death. ... We have a company that's charged with curing all viral disease, we have a company that's charged with curing several types of cancer. These are not things that are incremental approaches. It's all fine and good to have a drug that extends life by a certain amount of months or makes living with a disease easier. That's not what we're looking for. We are not looking for incremental change. We are looking for absolute cures in anything we do."

Link: http://www.cnbc.com/id/46342312

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

As an idle line of thought, what could you have done to yourself today in the field of cutting edge medicine and biotechnology at a moderate to high cost, setting aside the oppressive prohibition of medical regulation? Absent entities like the FDA - and a million other government employee busybodies who itch to regiment and enforce every aspect of our lives - it would be perfectly possible to get out there and solicit deals with researchers and clinics to try new things. To take your own estimate of risk and benefit, rather than being forced to wait for years or decades longer for medical technologies that might in the end be blocked entirely thanks to regulatory costs.

But what could you do today in world that was more free, and with enough money to pay for a major medical procedure? Here are a few examples with varying risk-reward profiles, pulled from the air:

• Have your aging immune system wiped out with chemotherapy and replaced from your stem cells. Your wager here would be that undergoing chemotherapy (not a wonderful experience under the best of circumstances) will cause you less harm in the long term than keeping your original, increasingly misconfigured immune system. Alternately, you could wait a decade for targeted cell-killer therapies demonstrated in mice to become a practical concern in humans.
• Undergo any one of a number of potential enhancing gene therapies. For example, why not pay your way into possessing a myostatin mutation? That boosts muscle mass, increases resistance to a range of age-related conditions, and otherwise seems to be beneficial all-round in mammals.
• Purchase stem cell infusions of the sort that seem to be at least modestly helpful for any number of degenerative conditions - a better option than traditional pharmaceutical medicines. But of course you can't do that in the US, just like you can't benefit from near all of the most recent advances, locked away in trials for years yet. You'd have to head overseas as a medical tourist to become a customer of the more reliable clinics in Asia or the Middle East.
• Decide in your healthy old age that the possible benefits outweigh the risks for infusion-based biphosphonate therapy. Of course you can't obtain that legally as a healthy person - those regulators again, deciding that they know better and anyone who disagrees with them will ultimately wind up in jail.
• Choose to end your own long-lived life in a safe and painless way at the time of your choosing, while attended by cryonics professionals who can provide an immediate and expert preservation - offering absolutely the best chance of later restoration with minimal damage, while keeping the cost to a sensible minimum thanks to scheduling.

I could go on - that just scratches the surface. But of course any group that gathered in the US to try these things, or offer services, or make the process as safe and transparent as possible would quickly find themselves prosecuted and jailed. The land of the free long ago ceased to have much to do with liberty or personal freedom. Freedom is the freedom to take your own risks and pay the costs if you pull a bad card from the deck - and that freedom is exactly what drives progress. Take it away and what results is the regulatory stagnation you see in medicine today.

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

Here is another paper suggesting that resveratrol isn't necessarily a great place to be spending hundreds of millions of dollars on research and development, given the poor results in studies that evaluate its effects. In an ideal world this money that would go towards improving biotechnology rather than the old-school approach of mining the natural world for compounds that maybe do more good than harm: "Resveratrol has shown evidence of decreasing cancer incidence, heart disease, metabolic syndrome and neural degeneration in animal studies. However, the effects on longevity are mixed. We aimed to quantify the current knowledge of life extension from resveratrol. We used meta-analytic techniques to assess the effect resveratrol has on survival, using data from 19 published papers, including six species: yeast, nematodes, mice, fruitflies, Mexican fruitflies and turquoise killifish. Overall, our results indicate that resveratrol acts as a life-extending agent. The effect is most potent in yeast and nematodes, with diminished reliability in most higher-order species. Turquoise killifish were especially sensitive to life-extending effects of resveratrol but showed much variation. Much of the considerable heterogeneity in our analysis was owing to unexplained variation between studies. In summary, we can report that few species conclusively show life extension in response to resveratrol. As such, we question the practice of the substance being marketed as a life-extending health supplement for humans."

Link: http://dx.doi.org/10.1098/rsbl.2012.0316

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

Via EurekAlert!: "Reproductive and somatic aging use different molecular mechanisms that show little overlap between the types of genes required to keep oocytes healthy and the genes that generally extend life span. ... The different genetic pathways help explain why a woman's fertility begins to decline after she is 35 years old, while her other cells do not show significant signs of aging until decades later ... To compare the molecular mechanisms that are switched on or off with the aging of oocytes and somatic cells, Murphy's lab turned to the model organism, Caenorhabditis elegans (C. elegans), the worm-like nematode that set off the whole field of longevity research with the discovery in the 1990s that gene mutations affecting insulin regulation doubled the worm's life span.Using DNA microarrays to measure the expression levels of genes, Dr. Murphy and her colleagues noted a distinctive DNA signature for aging oocytes. They also found that the oocytes of aging insulin and transforming growth factor-beta (TGF-beta) mutant mice had the same DNA profile that characterized young females. The researchers then compared the oocyte gene expression patterns with microarray transcription data on worms carrying the famous long-life mutations. Murphy and her colleagues found that even though somatic and reproductive aging in C. elegans both involve the insulin regulation pathway, the molecular mechanisms to maintain youthful oocyte function and to combat body aging are very different. ... It seems that maintaining protein and cell quality is the most important component of somatic longevity in worms, while chromosomal/DNA integrity and cell cycle control are the most critical factors for oocyte health."

Link: http://www.eurekalert.org/pub_releases/2011-12/asfc-ahb112211.php

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

There is a great deal of denial floating around when it comes to the excess weight carried by a majority of the people fortunate enough to live in wealthier parts of the world - even more denial than there is for lack of exercise, and there's plenty of that. Wealth is ever a double-edge sword, and brings the opportunity to become overweight and sedentary along with its many benefits - we mammals have evolved to find it hard to turn down large amounts of food that is both cheap and good, and we've succeeded ourselves into a challenging position on that front. Unfortunately indulgence has meaningful costs: a deterioration in health and life expectancy, and the more we overeat the worse that cost becomes. This has always been the folk wisdom of past decades and centuries, but in recent years the life science and medical research communities have brought more rigorous measurement and greater understanding to the costs of excess fat tissue and lack of exercise. Denial is becoming harder - which is a good thing, as the cost of food will continue to head towards zero as technology advances.

Here's an article written by someone who would love to remain upon the boat of denial by the sound of some of the later paragraphs, but it's hard to argue against facts established through good science:

When it comes to lowering our overall risk of death and dying from heart disease, fitness may be just as important, if not more so, than weight. That's what researchers concluded after studying fitness, weight and mortality among 14,345 middle-aged men in an 11-year study. Most studies that have previously linked weight gain, overweight and obesity to higher mortality risk have focused only on BMI, or body mass index, a ratio of height and weight. That's because weight can indirectly affect a number of different metabolic processes that contribute to mortality, such as how we burn calories or process sugars, and how high our blood pressure is. But weight may also be masking the effect of another factor that could protect or propel us to an early death: how efficiently our hearts and lungs are working, or, in other words, how fit we are.

Regular readers here will already know that both exercise and level of body fat go a fair way towards determining the future trajectory of health and life expectancy. Certainly there is no medicine or therapy that a healthy person can obtain at this time that comes even close to the benefits gained by (a) regular exercise, and (b) maintaining an optimal level of body fat. A handful of posts from the archives, for example:

• Exercise, Longevity, and Long Term Medical Costs
• On Aging and Exercise
• Exercise Slows Many of the Consequences of Aging
• There Are Old People and Fat People, But Few Old Fat People
• Don't Get Fat, and Don't Stay Fat
• More Evidence for the Costs of Visceral Fat

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

What is the Vegas Group initiative setting out to achieve, in a nutshell? I'm still working on that short explanation, but here is one attempt at it. Thanks to the present regulatory situation in the US - where aging is not recognized as a disease, and therefore no therapy for aging can be legally developed - there are any number of potentially useful biotechnologies presently languishing without further development. These are methods and techniques shown to extend life in mice or repair and reverse specific biochemical aspects of aging, but for which there is no further funding for clinical development. Nothing may be happening for these technologies in the US, but there are active biotechnology and medical development communities in other parts of the world who are not so encumbered by local regulation: many of the developed Asia-Pacific countries, for example. What the Vegas Group initiative ultimately aims to do is build a bridge between these undeveloped technologies and the developers who could bring them into the clinic for human use.

How will that bridge be built? I believe that the growing garage biotechnology and DIYbio communities will play a pivotal role in the US - validating, documenting, and lowering the cost for overseas ventures to pick up and further develop longevity therapies. From my perspective then, the very earliest actions for the first Vegas Group volunteers involve building the foundations for a repository of how-to documentation: guides that clearly explain how the garage biotechnology community could validate and further develop the best and latest techniques in longevity science.

At the outset this is less a matter of writing documents and more a matter of figuring out a sustainable process and organizational structure - the business of freelance writing is much akin to herding cats even when money is involved.

So I can envisage a guiding council of advisors putting together a plan for the hierarchy of topics they would like to see in the Vegas Group codex, from basic methods in biotechnology through to best attempt reverse engineering of things we know to be possible and that have been published: such as Cuervo's work on restoring youthful levels of autophagy, or protofection to replace mitochondrial DNA. The end result of that process might look something like a distillation of Fight Aging! mixed with the very elegant materials produced by the Science for Life Extension Foundation.

Codex project volunteers would then run an ongoing process of hiring post-graduates and interested researchers to write, and passing the results to starving authors who improve the output to a quality suitable for the open biotechnology community. There would of course be some back and forth between the post-graduates and the starving authors in order to reduce the inevitable translation errors, but I see this as a viable way to produce a body of knowledge that is sufficiently good to begin with - not perfect, not even necessarily very good, but sufficient.

I mentioned rejuvenation of autophagy above as one of the possible projects for documentation, and at present, the Vegas Group discussion list is focused on mitochondrial protofection - and we could certainly use another life science volunteer or two to help lay out the skeleton for full documentation, or work on one of the other potential projects. If you're interested, come on over and join in.

Some of the other possible projects that have been mentioned or came to mind include the following:

1) LysoSENS

LysoSENS isn't an established methodology, but it is an ongoing research program that aims to find bacterial enzymes capable of breaking down harmful aggregates that build up with age. This is a matter of synthesizing the chemicals to be broken down, digging up some dirt from likely locations, culturing bacteria, and matching them up against your unwanted chemicals to see if you have a hit. This seems like an excellent project for DIYbio enthusiasts - someone is going to find an existing bacterial strain containing enzymes that can be adapted to safely destroy lipofuscin in human cells, and there's no reason that person has to be working in an institutional establishment.

2) Manufacturing Targeted Mitochondrial Antioxidants

A number of research groups have been publishing in recent years on ingested targeted mitochondrial antioxidants that appear to slow aging in mice. It seems a viable sophisticated garage or shared lab-space chemistry experiment to replicate their published work, and then a biotech experiment to validate your synthesized antioxidants in cell cultures.

3) Upregulation of PEPK-C

This is a manipulation of gene expression show to increase longevity in mice. As gene engineering goes, this is about as straightforward as it is going to get - which is to say still a fair hurdle for the garage biotech community to work towards - a single gene altered, and an impressive result. Managing to document the process sufficiently well to recreate this intervention in cell cultures would be, I think, a real showpiece for a laboratory cooperative.

Now all of these items, when carried out as projects, can be expected to sit atop a pyramid of supporting techniques and documentation, some of which will be common to many different projects. Producing that material sufficiently well will, I think, help in the growth of the garage biotechnology and DIYbio communities. Documentation is key for newcomers and recruitment, and you can never have too much of it.