Longevity Meme Newsletter, November 23 2009

November 23 2009

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.



- Coverage of the Manhattan Beach Project Summit
- A Selection of Calorie Restriction Research
- Discussion
- Latest Healthy Life Extension Headlines


Ronald Bailey reported the recent Manhattan Beach Project longevity summit this past week:


"If you're under age 30, it is likely that you will be able to live as long as you want. That is, barring accidents and wars, you have centuries of healthy life ahead of you. So the participants in the Longevity Summit convened in Manhattan Beach, California, contend. Over the weekend Maximum Life Foundation president David Kekich gathered a group of scientists, entrepreneurs, and visionaries to meet for three days with the goal of developing a scientific and business strategy to make extreme human life extension a real possibility within a couple of decades. Kekich dubbed the effort the Manhattan Beach Project.

"Anti-aging research is a rich and varied territory right now. Researchers are finally beginning to get a handle on the actual causes of aging. With this increased scientific understanding, some researchers now believe they are on the way to figuring out how to stop it, and - eventually - how to reverse it."


The dominant theme at Fight Aging! this past week was research into the biochemistry of calorie restriction. It's a rich and very active field; scientists in the mainstream of aging research are mining this vein in search of genes and proteins that can be targeted to capture the health and longevity benefits of eating less food while still obtaining the optimal amount of micronutrients and vitamins.


"Studies of the biochemistry of calorie restriction (CR) in humans are being held in a number of research institutes in the US. So far, as expected, the beneficial biochemical changes caused by CR in humans look very much like the biochemical changes observed in mice, rats, and rhesus monkeys. That bodes well for a gain in human life span as a result of this practice, though at the present level of available biotechnology there is little option but to wait and see what the results will be on that count. The consensus amongst biogerontologists appears to be that CR will extend human life span by a handful of percentage points, but practitioners of calorie restriction would be expected to evade or resist all of the common age-related diseases."


"A short introduction to the gene PGC-1alpha: this is one of a number of genes of interest involved in the biochemical changes, resistance to age-related disease, and extended healthy life span brought about by calorie restriction (CR). It favorably changes the operation of mitochondria, and based on the effects of other genes and proteins involved in these mechanisms, I would expect enhanced expression of PCG-1alpha to have at least some modest beneficial effect on life span."


"One of the better research outcomes a biologist can hope for is to find that a particular mechanism, disease, or benefit has a single point of control somewhere in its web of interlinked genes and feedback loops. A single gene or protein that acts as a switch or a dial, and has no or few entanglements with other biological systems. ... Researchers engaged in picking apart the mechanisms underlying calorie restriction might still manage to uncover a simple switch somewhere in amidst the all complexity and chains of genes and proteins turning one another on and off. They've been hacking away the brush for some years now, but there's no shortage of undergrowth yet to be cleared."


"Intermittent fasting and calorie restriction are two ways of reducing your calorie intake to obtain health benefits. Intermittant fasting might be accomplished by eating every other day, for example, while calorie restriction means eating every day, but eating less. In both cases, you have to make sure your intake of micronutrients is optimal, and your physician agrees, as for any sane dietary choice. ... intermittent fasting quickly hits one of the same biochemical triggers as calorie restriction: TOR, or target of rapamycin, which in turn boosts the process of autophagy ... More autophagy is a good thing; more aggressively cleaning out damaged cellular components should extend functional life span by lowering the rate at which further damage accumulates, and there is a fair weight of scientific evidence behind that viewpoint."


The highlights and headlines from the past week follow below.

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Here's a calorie restriction (CR) article I missed from earlier this month: "If anyone is in a position to assess the risks and benefits of CR, it is Dr. Luigi Fontana, research associate professor of medicine at Washington University. He is overseeing a group of 50 patients involved in an 11-year study of calorie restriction. The study is part of CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a large clinical trial being funded by the National Institute on Aging ... Why is CR controversial in the United States? Dietitians seem opposed to this. ... First of all, probably most dietitians don't have knowledge about calorie restriction. These are pretty new data. Before they were only on mice and rats. So they say, 'OK, mice and rats, who cares about mice and rats?' And so this is a pretty new phenomenon, and any time there is a new phenomenon, there are a lot of people who say, 'No, no, no, no, no!' It's a typical reaction to something that is new. ... All the metabolic, hormonal and cellular adaptations so far we have seen in mice and rats, we know they are living longer, not only healthier but longer. We know that is also happening in monkeys and in humans."

Researchers have succeeded in tissue engineering fully functional and complete skin patches from stem cells: the scientists recreated "a whole epidermis from human embryonic stem cells. The goal is to one day be able to propose this unlimited resource of cells as an alternative treatment in particular for victims of third degree burns and patients with genetic diseases affecting the skin. ... Human embryonic stem cells (hES) have two fundamental characteristics: a capacity for unlimited proliferation and pluripotency i.e. the capacity to differentiate into all the cell types in the human body. The first objective of the team was to obtain skin stem cells (keratinocytes) similar to those naturally present in the human epidermis from hES cells. Keratinocytes, permit the constant renewal of the skin. Once this stage was achieved, the second objective of the researchers consisted in finalising strategies to isolate keratinocyte stem cells in order to test their capacity to reconstitute a functional epidermis firstly in vitro -- then in vivo. ... Twelve weeks after transplantation, the mice presented localized areas of completely normal and functional adult human epidermis containing all the skin cell types."

Advanced Cell Technology (ACT), one of the oldest companies formed specifically to develop regenerative medicine, is setting up for another round of human trials based on its work: "it has asked for approval to test human embryonic stem cells in treating a rare cause of blindness. The company said it filed an IND, an investigational new drug application, with the U.S. Food and Drug Administration to use the stem cells to treat patients with Stargardt's macular dystrophy. If approved, it would be the second U.S. approval to test human embryonic stem cells in human patients. ... ACT has previously reported it used human embryonic stem cells to make retinal cells. They have reversed blindness in rats. ... The treatment for eye disease uses stem cells to re-create a type of cell in the retina that supports the photoreceptors needed for vision. These cells, called retinal pigment epithelium (RPE), are often the first to die off in Stargardt's macular dystrophy. ... It has been over a decade since human embryonic stem cells were first discovered. The field desperately needs a big clinical success. After years of research and political debate, we're finally on the verge of showing the potential clinical value of embryonic stem cells. Our research clearly shows that stem cell-derived retinal cells can rescue visual function in animals that otherwise would have gone blind. We are hopeful that the cells will be similarly efficacious in patients."

From CNN: "This special edition of Vital Signs: The Clinic will be broadcast LIVE on CNN.com [on November 30th] and we want you to take part in the conversation. ... Vital Signs host and CNN Chief Medical Correspondent, Dr. Sanjay Gupta will be joined by best-selling author Dan Buettner who has done extensive studies on the areas in the world people live the longest, healthiest lives, known as Blue Zones, and shares their formula for a long life.
The other panelist is geneticist Dr. Aubrey de Grey, who believes regenerative medicine could, in a matter of decades, extend life expectancy to 1000 years. What would you ask the experts? Do you want to learn how to live until 100 and beyond? Or find out which diets or exercise to follow for living longer?" These are good examples of the two very opposite ends of the respectable pro-longevity community. The Blue Zones material is (to be charitable) just a branding of what is known of the relationship between good health practices in diet and exercise and human longevity. Aubrey de Grey's Strategies for Engineered Negligible Senescence, on the other hand, are a serious examination of how to greatly extend healthy human life span through near-future research and development.

From the Age Management Medicine Group, a diagram-rich article based on a presentation given by one of the folk from the Supercentenarian Research Foundation: "A Supercentenarian is anyone age 110 years or older. ... While the number of centenarians has been rising exponentially, the number of supercentenarians has remained flat. ... The most likely cause of death of Supercentenarians is called Senile Cardiac TTR-Amyloidosis ... SRF (Supercentenarian Research Foundation) has performed eight autopsies [of supercentenarians so far and six] of the eight cases have TTR-Amyloidosis as their common cause of death. This is the invisible barrier. ... Why do Supercentenarians live as long as they do? (How do they escape from chronic diseases, such as Heart Disease, Cancer, Stroke, Diabetes, and Alzheimer's Disease, which are the top diagnoses written today on Death Certificates in the US and limit the average life expectancy of older Americans?) Why don't they live longer than they do? (TTR Amyloidosis could be the Grim Reaper waiting in the wings for everyone, unless we figure out what to do about it first)."

Even comparatively crude autologous stem cell transplants provide benefits for heart disease patients: "The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells. In the 12-month Phase II, double-blind trial, subjects' own purified stem cells, called CD34+ cells, were injected into their hearts in an effort to spur the growth of small blood vessels that make up the microcirculation of the heart muscle. Researchers believe the loss of these blood vessels contributes to the pain of chronic, severe angina. ... The stem cell transplant is the first therapy to produce an improvement in severe angina subjects' ability to walk on a treadmill. Twelve months after the procedure, the transplant subjects were able to double their improvement on a treadmill compared to the placebo group."

One class of the new generation of cancer therapies presently under development uses targeted viruses to kill cancer cells. Here is an example of the type: "BioVex Inc, a company developing new generation biologics for the treatment and prevention of cancer and infectious disease, announced today that the data from its completed Phase 2 clinical study ... [the therapy] is a first-in-class oncolytic, or cancer destroying virus, that works by replicating and spreading within solid tumors (leaving healthy cells unaffected), thereby causing cancer cell death and stimulating the immune system to destroy un-injected metastatic deposits. Both modes of action have been clearly validated in the clinic, where multiple patients with metastatic disease progressing at enrollment have been declared disease free. ... Previous clinical trials have enrolled patients with breast cancer, melanoma, head and neck cancer and pancreatic cancer, with indications of clinical activity being observed in each. The Company recently commenced a Phase 3 study in metastatic melanoma." Therapies with few side effects and even low rates of success against metastatic cancer are a big deal. The success rate will only improve with time, and is already far greater than that of any presently widespread treatment option.

A piece at h+ Magazine briefly examines the efforts of members of the cryonics community to set up legal frameworks that stand a good chance of preserving wealth across decades of being considered legally dead. In the long term, you can't take it with you: any undefended resource will eventually be stolen one way or another, no matter what laws and contracts say. But in the shorter term, and for small groups of people, this legal approach is a fair strategy: "The laws are complicated, and not stacked in your favor, but if done carefully it's possible to leave a huge death benefit payoff from your life insurance policy to your cryonically-preserved self. And since life insurance can also be used to finance your cryopreservation, you need not wait until you are rich to sign up. Most in the middle class, if they seriously want it, can afford it now. So by taking the right steps, you can look forward to waking up one bright future morning from cryopreservation the proud owner of a bank account brimming with money. Don't get me wrong. Leaving money to your future self is complicated. The courts have decided that cryopreserved people are not suspended or preserved. Rather, they are irrevocably dead, and by being dead have no legal right of ownership or inheritance. These laws may change if the first cryopreserved people are resuscitated and sue for some new kind of civil rights, but that could be decades away. In the meantime, those who are not yet being preserved have spent years pondering and discussing possible methods of self-inheritance. They call it Cryonics Estate Planning and there are now at least three ways to achieve the goal."

From the Times: "Over the past decade increasing understanding of both adult and embryonic stem cells has opened a new frontier for science through regenerative medicine. As research has revealed how the body's master cells can be coaxed to form new tissue, it has raised the prospect of producing new organs to replace those that have been damaged. Growing new cells with specialised functions, however, is only the first hurdle that has to be cleared before regenerative medicine can help patients. A clump of cells is rarely, by itself, much use to anybody. They also need to be properly plumbed into blood vessels, to be protected from the body's immune system and to be structured in a shape that allows them to perform. This means that regenerative medicine is not reliant only on the cell biologists who can coax stem cells to make the right sort of tissue. It also needs engineers and immunologists. It is by its nature an interdisciplinary field. ... As fast as this technology is advancing, however, there is still a long way to go before scientists can re-create more complex organs. Professor Hollander said: 'The early successes have involved organs without moving parts or complicated biology.' The creation of new breasts, windpipes and bladders is an amazing step forward for medicine, but it remains a different challenge to grow new hearts or livers."

From the BBC: "Researchers in Australia plan to test a medical 'scaffold' designed to stimulate natural breast tissue to regrow following surgery. Doctors [will] test the technique next year in a trial involving six patients. The team say that the permanent fat found in breasts can be grown inside this contoured scaffold. They claim to have successfully tested the device in pigs. ... when the 'empty chamber' is implanted, fat tissue will naturally fill it to form a new breast. This chamber will also contain a gel made using the patients' muscle cells to 'induce fat tissue production'. ... the attractions of this approach were its simplicity and the fact that the tissue growth occurred inside the body. ... At the time of implanting the cells the surgeon redirects the vasculature of the body which keeps a good blood supply to the implant. That is in itself nothing new, but combining it with a cell implant is an interesting step. ... the technological advance was the use of a biomaterial cage used to trap the cells in the right place. In future, the team plan to make this cage biodegradable so it does not have to be removed."



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