Longevity Meme Newsletter, October 19 2009

October 19 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.



- Falsely Expecting a Gentle Upward Slope
- Russian Metabolic Manipulation Research
- Alternate Day Fasting Continues to Look Promising
- Is Epigenetic Disarray a Cause of Aging?
- Discussion
- Latest Healthy Life Extension Headlines


Radical change lies ahead and radical change lies in our immediate past, yet most people expect the future to look like a gentle slope of upward progress. This is strange:


"People generally expect the future to be much like the present, but with shinier toys. They expect their lives to look like the lives of their parents, albeit with those shinier toys, and are deeply skeptical of predictions of radical change. At one and the same time, these folk take for granted the radical change that has taken place across their lives to date, and that was neither foreseen nor expected by their parents.

"While going through old SF magazines, I found mention of Atlantic Richfield's ad campaign requesting vision statements from Americans of what life might be like in the Tricentennial [in 2076]. ARCO received some 60,000 responses and in 1977 published an 80-page booklet summarizing those visions. The SF reviewer stated that most of the visions listed therein would have seemed old-hat to SF fans in the 70s. As in 20 to 30 years out of date. ... In short, [people predicted that] life would be like 1976 in 2076, only more so. No hint of the telecommunications revolution that was already well underway in 1976. No hint of the things young men named Gates and Jobs were up to. Nor any discussion about what that then newfangled computer network, the Arpanet, might grow into."

Biotechnology is just getting started. Today these life science technologies are at an early stage, just like computing and telecommunications in the 1970s. What lies ahead is enormous potential for progress in medicine and biomedical engineering - and thus also for extending healthy life. The 2040s will be as profoundly different to today as today is from the 1970s.


The Russian community of longevity researchers bears strong similarities to the English-language community of longevity researchers. Both communities have ties to transhumanist advocacy groups and cryonics organizations, for example, and both largely focus on manipulating metabolic processes to slow down aging. These days - days in which a great deal of investment is flowing into metabolic manipulation research and development in the US - I am seeing more English language publications from the Russian longevity science community:


"A number of small peptides have been isolated from different organs and tissues and their analogues (di-, tri-, tetrapeptides) were synthesized from the amino acids. It was shown that long-term treatment with some peptide preparations increased mean life span by 20-40%, slow down the age-related changes in the biomarkers of aging and suppressed development of spontaneous and induced by chemical or radiation carcinogens tumorigenesis in rodents."


With all the interest in calorie restriction, forms of intermittent fasting are now being examined more closely. As for calorie restriction, researchers are trying to understand the biochemical basis for the resulting health and longevity benefits:


"Intermittent fasting isn't as well researched as calorie restriction - by which I mean to say the evidence for health benefits is 'only' very good rather than overwhelming, as in the case of calorie restriction. It's worth noting that there exist intriguing hints that the underlying biological mechanisms by which these benefits are conferred are different for these two strategies, despite the basic similarity: eating less while still obtaining all the necessary nutrients. "


Epigenetics adds a whole new level to the existing debate over whether accumulated mutational damage to nuclear DNA over a lifetime is or isn't an important contributor to the aging process:


"Your DNA is a blueprint for the protein components of the machinery of your metabolism and structure as a living organism. Gene expression is the process by which a part of the DNA blueprint is interpreted into instructions to build a protein, and epigenetics is the study of ways in which things other than changes in DNA can cause changes in gene expression. The blueprint may be the blueprint, but the execution of that blueprint is a shifting and very complicated process.

"Epigenetics, it has to be said, is an unfolding and early-stage field. It's poorly understood. People are still arguing over whether accumulated nuclear DNA damage is significant in human aging, so of course it should be taken as read that there are also debates over whether epigenetic changes are significant in aging. Yes, the blueprint is getting smudged, and yes, the interpretation of that blueprint looks like it's changing - but is that actually important in comparison to the other known forms of age-related biochemical damage?"


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




Another example of progress in tissue engineering from the Boston Globe: "researchers have created a strip of pulsing heart muscle from mouse embryonic stem cells, a step toward the eventual goal of growing replacement parts for hearts damaged by cardiovascular disease. ... I think over the last five years or so, we've made great progress in being able to guide stem cells into whatever cell type we want, in this case the heart ... For years, scientists have been able to turn embryonic stem cells into a variety of heart cells, producing dramatic videos of cells beating in a dish. In the new work, [biologists] first isolated a progenitor cell that would only give rise to ventricular muscle cells - the working muscle that drives blood around the body, and the tissue that is damaged during a heart attack. Then, collaborating with biomedical engineers, they seeded those cells on a thin film that had been engineered in such a way that it encouraged them to begin to form cardiac muscle." This doesn't seem quite as far along as some other groups, and it's still far behind what can be done with decellularization and a donor organ - but progess is underway.

If you look at research into the fundamental biological mechanisms of healing, you'll quickly see that we mammals are not optimally evolved. There are all sorts of changes and tweaks that may allow far greater regeneration in specific circumstances, such as nerve injury. Here is one example: "Scars can serve as double-edged swords in spinal cord injuries ... The scar forms a wall around the wound, preventing the injury from spreading, but [releases] molecules that keep severed nerve fibers from passing the damaged tissue, so they cannot connect with their original targets to restore motor and sensory function. ... [researchers have] identified where these potent molecules - called chondroitin sulfate proteoglycans (CSPGs) - bind to the surface of neurons, exposing a novel therapeutic target. ... This discovery suggests that we might be able to treat central nervous system injuries with a pill in the future ... It's hard to overcome CSPGs in the human body, but receptors may offer an easier target ... follow-up experiments in culture dishes on neurons missing the receptor - called PTP sigma - and studies in mice confirmed the connection. ... [researchers] observed unprecedented levels of growth in the neurons of injured mice missing the PTP sigma receptor. In fact, motor neurons sent extensions all the way through the scar and well beyond the wound."

A fairly cautious article here on current work to stimulate the production of dopamine in Parkinson's patients: "Macaque monkeys that received gene therapy for symptoms of Parkinson's disease saw a significant improvement in their motor function without the side effects associated with current standard therapy ... For the past 40 or so years, the treatment of choice for Parkinson's has been so-called dopamine replacement therapy, which uses drugs to increase dopamine levels in the brain. The approach helps, but because the infusion of dopamine takes place in fits and bursts, not continuously, people often develop involuntary movements. Scientists have thus been focused on finding ways to deliver dopamine to the brain more continuously. Simultaneous insertion of three genes allowed certain cells in the brain to take over production of the neurotransmitter dopamine. ... But even if this gene therapy approach were to someday produce good results in humans, it still would not solve many of the myriad other problems associated with Parkinson's. ... the gene therapy would be considered a treatment rather than a cure because it 'corrects only dopamine-related symptoms.' ... an early-phase clinical trial in humans is in progress. ... So far, six Parkinson's disease patients have been treated - no serious adverse events, encouraging results so far. [But] the study is not ended, so still no final results."

Via EurekAlert!: researchers have made "the unexpected finding that when the brain's immune cells (microglia) are activated by the interleukin-6 protein (IL-6), they actually remove plaques instead of causing them or making them worse. The research was performed in a model of Alzheimer's disease established in mice. ... [Researchers] initially set out to prove that the activation of microgila trigger inflammation, making the disease worse. Their hypothesis was that microglia would attempt to remove the plaques, but would be unable to do so, and in the process cause excessive inflammation. To the surprise of the researchers, when microglia were activated by IL-6, they cleared the plaques from the brains. ... researchers then set out to determine exactly how IL-6 worked to clear the plaques and discovered that the inflammation induced by IL-6 directed the microglia to express proteins that removed the plaques. This research suggests that manipulating the brain's own immune cells through inflammatory mediators could lead to new therapeutic approaches for the treatment of neurodegenerative diseases, particularly Alzheimer's disease."

Many diseases, such as cancer, are curable - or at least treatable - using today's technology if they can be detected in their very earliest stages. Therein lies the challenge, of course. Here, a glance at one initiative emblematic of present research and development efforts in this direction: Leroy Hood of the Institute for Systems Biology "has secured $30 million in venture capital for a startup that aims to detect cancer and neurodegenerative diseases like Alzheimer's in their earliest and most treatable stages. ... It will make it possible for doctors to diagnose diseases much earlier; it will open the door to more individually tailored therapies that will have much greater odds of success; and it will allow doctors to follow up with patients to see if treatments they prescribe are really working at the molecular level ... My view is that P4 medicine - predictive, preventive, personalized, and participatory - will emerge over the next five to 20 years, and this is the first step. This is going to be the platform in the initial days ... We are optimistic that systems biology will become a critical tool in the development of personalized medicine." You might recall that Hood has said he thinks an additional decade or two of healthy life is possible through use of this sort of technology platform.

As immune therapies are developed further, researchers will be increasingly incentivized to find ways to repair and restore age-damaged immune systems to youthful effectiveness. Most work on immune therapy is aimed at cancer and other diseases of the old, after all: "Elderly cancer patients need a combination of treatments tailor-made to their specific needs to successfully combat the disease. The challenge is to boost their immune response to cancer vaccines, because like the rest of our organs, our immune system ages and gradually becomes less efficient as we get older. ... Aging of the immune system coincides with higher rates of cancer in the elderly. There is a wealth of research on the effects of harnessing the power of the body's own immune defences to recognize and destroy tumors (immunotherapy), yet very little of this work takes into account the effects of aging on the immune system. Older individuals do not respond to vaccine therapy as well as younger adults. ... The immune system of the elderly is very different from the young and it is difficult to extrapolate results obtained in the young, for use in the old. Our job in the next few years is to figure out how to robust the old immune system by understanding, at a molecular level, its intrinsic defects to properly stimulate antitumor responses. Only then can we successfully customize tumor vaccines to be effective for the treatment of tumors in the old."

2009 HUMANITY+ SUMMIT IN DECEMBER (October 13 2009)
The humanity+ transhumanist advocacy group - the new face of the old World Transhumanist Association - will be holding their yearly meeting in December: "Humanity will be radically changed by technology in the (possibly quite near) future. We foresee the feasibility of redesigning the human condition, including such parameters as the inevitability of aging, limitations on human and artificial intellects, unchosen psychology, suffering, and our confinement to the planet earth. The possibilities are tremendously broad and exciting - and the H+ Summit will provide a venue to discuss them with like-minded individuals, and hear exciting, presentations by the leaders of the ongoing H+ r/evolution." There are many of the same speakers and topics on the program as for the recent Singularity Summit, so coverage of that event should give you a good idea as to what to expect. I see that open source medicine makes an appearance - the more of that the better. It's an important concept for the future of medical research; as the cost of biotechnology plummets, the field of those who can contribute meaningfully broadens, and if we're luckly we will see a research culture that looks a lot like - and is as productive as - today's vibrant open source software community.

Manipulating the insulin/IGF-1 signaling system is known to promote longevity in lower animals, and here is a demonstration of specific benefits to heart tissue: researchers "studied elderly mice genetically engineered to suppress the activity of one form of the PI3K gene, which is a part of the insulin/IGF-1signaling system that helps regulate the lifespan of cells. A variation of PI3K, known as the p110alpha isoform, plays an important role in tissue aging. Suppressing the isoform's activity in the roundworm C. elegans extends its life. And in fruit flies, suppression prevents the age-dependent decline of heart function. ... researchers compared aged mice with a functional p110alpha to aged mice with suppressed p110alpha and found that mice with the suppressed gene had: improved cardiac function; less fibrosis (fibrosis causes the heart to lose flexibility); fewer biological markers of aging; and a pattern of cardiac gene expression like that of younger mice. ... This study showed that aging of the heart can be prevented by modifying the function of insulin and paves the way to preventing age-associated susceptibility to heart failure."

Most people who sign up with a cryonics provider fund the cost of their future suspension using a life insurance policy. Rudi Hoffman is a long-standing member of the cryonics community and one of the few insurance agents to specialize in this type of policy: "The general feeling of the uninformed populace is that 'Cryonics is only for rich guys.' It is my passion, as well as my profession, to dispel this pernicious and potentially deadly lie. Cryonics is AFFORDABLE for most people who are in good health living in a developed country. This is because of the magical leverage of life insurance, in which a few dollars a day can create a fund of literally hundreds of thousands of dollars exactly when these funds are needed. ... Cryonics trusts exist to enable your funds to grow at a rate somewhat higher than taxes and inflation, and compound and grow. These funds are earmarked to both enable the cryonics resuscitation process, and enable you to have funds to provide you with enhanced options in the astounding future that you may be revived in. ... The bad news is that legitimate cryonics estate planning is not cheap. The better news is that some groundwork has been laid out by pioneers of this idea to make it more affordable than it used to be. And the actual funding of the cryonics trust can come from the leverage of life insurance."

From the BBC: "Scientists have created part of the jaw joint in the lab using human adult stem cells. They say it is the first time a complex, anatomically-sized bone has been accurately created in this way. It is hoped the technique could be used not only to treat disorders of the specific joint, but more widely to correct problems with other bones too. ... The joint has a complex structure which makes it difficult to repair by using grafts from bones elsewhere in the body. The latest study used human stem cells taken from bone marrow. These were seeded into a tissue scaffold, formed into the precise shape of the human jaw bone by using digital images from a patient. The cells were then cultured using a specially-designed bioreactor which was able to infuse the growing tissue with exactly the level of nutrients found during natural bone development. ... he availability of personalised bone grafts engineered from the patient's own stem cells would revolutionise the way we currently treat these defects. ... he new technique could also be applied to other bones in the head and neck, including skull bones and cheek bones, which are similarly difficult to graft."



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