Longevity Meme Newsletter, May 03 2010

May 03 2010

The Longevity Meme Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to the Longevity Meme.



- Colorful Brochures From the Methuselah Foundation
- An Impressive Targeted Cancer Therapy
- Thoughts on Animal Studies
- Discussion
- Latest Healthy Life Extension Headlines


The Methuselah Foundation volunteers have put out a great pair of PDF format brochures, just the thing to print out for conferences and to give to your friends:


"Aging is inevitable. Or is it? Alzheimer's, cancer, stroke and heart attack are among the familiar and dreaded results of aging. Knowing - but not wanting to accept - that fate we looked deeper to explore how and why our bodies age. We found that some of our questions had no answers even though scientists believe there is great untapped potential for understanding, reversing and solving the ravages of age. While we dreamed about the possibility of long, healthy lives for ourselves and our children, we realized something had to be done to fully explore the prospects for extending healthy human life.

"Methuselah Foundation was founded to do just that. We exist because we believe everyone should enjoy a vibrant and productive life, not just in the early years, but into their 70s, 80s and 90s. Our exploration showed that scientists are interested and eager to understand aging, find solutions and share them. What was lacking were the funds and incentive to make it possible. That is why Methuselah Foundation invests in great scientific research and awards performance based prizes."


Some of the work on targeting specific cell characteristics in the cancer research community is producing very impressive technology demonstrations. These and other evidence of progress are why I am less worried about the prospects of cancer in my future than I might be. Even advanced cancers can be destroying by sufficiently good targeting to the characteristic differences of a particular type of cancer cell:


"Scottish scientists have made cancer tumours vanish within 10 days by sending DNA to seek and destroy the cells. The system, developed at Strathclyde and Glasgow universities, is being hailed as a breakthrough because it appears to eradicate tumours without causing harmful side-effects. ... the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100% of the animals (90% complete response, 10% partial response).The treatment was well tolerated by the animals, with no apparent signs of toxicity."


We live in a world that is far from ideal. Yet by all measures we have greatly improved our surroundings, and the only way for this trend to continue is through further progress in technology:


"Animal experimentation is horrible and terrible. Even in the most ethical of studies suffering is inflicted upon animals that otherwise would not have happened; entire genotypes of animals doomed to additional suffering have been bred in some cases. But the alternative is far worse: to not perform these animal studies, or rather for some privileged group to use force to prevent others from performing such studies. For without animal studies there would be no meaningful progress in medical science. It is a harsh and unpleasant aspect of the human condition that forcing suffering upon animals in the course of scientific studies is necessary to advance both human and veterinary medicine. A few suffer for the benefit of many - an equation that should make any sane and compassionate person uncomfortable.

"Animal studies are even required to refine the science needed to move beyond animal studies. Ethics and morality aside, studies employing animals are expensive and time-consuming. Given the choice, scientists would much rather experiment on cells in a dish, or on slabs of unfeeling cultured tissue, or upon simulations of animals, if these methods would generate results of the same quality.

"In comparison to what might be and what is possible, we live in a barbaric age of suffering, war, death, and sundry other horrors that we like to keep behind the curtains and out of the mind's eye. But barbaric as it is, this age is far better than the past by all such measures. We no longer absolutely, definitely need to slaughter animals for food to sustain the populace, for example, and rates of violence between humans are far lower than in the pre-modern era of tribes and universal poverty. The option stands open today for a society of vegetarians: it is practical from a technological and economic standpoint. That we have not moved rapidly in that direction is our shame, and our descendants will look back on us as savages for this and many other reasons.

"Those people who criticize and take action against the use of animals in medical research should first look to their diets, and then to the practice of farming animals. Vast and expansive animal suffering is caused in the name of putting meat into the marketplace - greater many times over each month than in all the animal experiments in modern history. Persuade the omnivores of the human race to relinquish their participation in the meat market before savaging the medical science that will benefit both man and beast."


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!




An attendee at the Humanity+ UK 2010 conference offers thoughts on transhumanist goals: "The convergence of current technologies such as nanotechnology, biotechnology, information technology and cognitive science (NBIC) and future technologies such as artificial intelligence, mind uploading, cryonics, and simulated reality, is truly inspirational. ... I think we all have a vested interest in Aubrey de Grey's idea that aging is simply a disease, and a curable one at that. His plan is to identify all the components that cause human tissue to age, and design remedies for each of them through his approach called SENS (Strategies for Engineered Negligible Senescence). Once we can extend human life spans by thirty years, we're well on our way to immortality. Aubrey de Grey claims that the first human being to live a thousand years has probably already been born. From the way he talks, the biggest challenge in the race against mortality is funding! So I highly encourage those of you with means and an interest to donate to the SENS Foundation. ... Another fascinating speaker was David Pearce, advocating the abolition of suffering throughout the living world. ... He argues that as we develop these technologies, it is both our moral and hedonistic imperative to rid all sentient beings of pain."

Sequencing our own DNA and cross-referencing the results against the best of present scientific knowledge will soon be cheap and routine. This is an example of the sort of incremental progress in medical technology that is increasing human life expectancy year after year: a little more prevention here, a little better insight into how to cure there. From ScienceDaily: "For the first time, researchers have used a healthy person's complete genome sequence to predict his risk for dozens of diseases and how he will respond to several common medications. The risk analysis [also] incorporates more-traditional information such as a patient's age and gender and other clinical measurements. The resulting, easy-to-use, cumulative risk report will likely catapult the use of such data out of the lab and into the waiting room of average physicians within the next decade, say the scientists. ... The $1,000 genome is coming fast. The challenge lies in knowing what to do with all that information. We've focused on establishing priorities that will be most helpful when a patient and a physician are sitting together looking at the computer screen. ... Information like this will enable doctors to deliver personalized health care like never before. Patients at risk for certain diseases will be able to receive closer monitoring and more frequent testing, while those who are at lower risk will be spared unnecessary tests. This will have important economic benefits as well, because it improves the efficiency of medicine."

This EurekAlert! release looks at some of the challenges facing the increasing number of research groups who are attempting to destroy cancer stem cells: "Many of the colon cancer cells that form tumors can be killed by genetically short-circuiting the cells' ability to absorb a key nutrient, a new study has found. While the findings are encouraging, the test tube study using human colon cancer cells also illustrates the difficulty of defeating these cells, known as cancer stem cells (CSCs). ... It is becoming more evident that only a small number of cells in the tumor are capable of forming the tumor, namely the cancer stem cell. So the new strategy is to eliminate the cancer stem cells and thus lower the recurrence of cancer. ... Because CSCs have properties similar to normal stem cells, we have to find a way to attack them while keeping the adult stem cells alive. ... To do that, the research team inactivated a receptor that is found in increased amounts in colon cancer cells: the insulin-like growth factor receptor (IGF-1R). The colon cancer CSCs seem to need a fair amount of IGF to live, more than other cells, and they can't function without the IGF receptor. ... Working with human colon cancer cells, the researchers manipulated the cellular genetics using small interfering RNA (siRNA) to prevent the synthesis of IGF-1R. In this way, they reduced the number of IGF receptors by half, and reduced the number of CSCs by 35%."

From TechNewsWorld: "During his homily this Easter, Pope Benedict argued that medical science, in trying to defeat death, is leading humanity toward likely condemnation. It's a position at odds with the value of life, one that the Church will likely revise years from now, replaying the institution's embarrassment over censoring Galileo. ... If scientists are successful in finding techniques to rebuild cartilage, repair organs, and cure cancer, people will indeed be living longer - but they will also be healthier, more energetic and youthful. Health-extension, when it happens, will allow people to live longer, better. Consider that 60-year-olds today are not in the same shape as their counterparts were in the 1800s or 1900s. As humans discovered how to take better care of themselves, through improved nutrition, the use of antibiotics and other techniques, 'chronological age' became less synonymous with 'biological age.' That is, many of today's 60-year-olds act and feel much younger than one might expect. The average human life expectancy today is close to 80 years but in 1850, it was 43 years, and in 1900 it was 48 years. One can imagine someone in 1850 arguing that doubling life expectancy would be terrible, because innovation might be at risk and there would be more old people around. But would anyone today say they are sorry that science made it possible to live longer and healthier lives?"

An interesting article: "In what turned out to be his final official engagement as CEO of Sirtris Pharmaceuticals, Christoph Westphal offered some key lessons in how to build a successful biotech company ... It's pretty amazing ... in the last 20 years, we've gone from zero understanding of the genes that play a role in aging to a pretty clear understanding that IGF1 plays a role, MTOR, the Sirtuins play a role, there's 10-15 genes play a role. Many of those are going to be druggable targets. Will Sirtris be successful? I don't know. It's still going to be very risky. But I'll be shocked if there are not drugs in the next 10-15 years that target genes that control aging. ... Westphal did not shirk from addressing the ongoing controversy surrounding the physiological activity of some Sirtris compounds. ... There's a debate in the academic world. We don't know the specific molecular mechanism of why you need a specific substrate on the in vitro screen to find Sirt1 activators. ... It's a numbers game and it's gotten harder with the FDA ... People are spending less on pharma R&D and more on consumer health care and trying to diversify into developing countries and away from Europe and the United States. Fewer drugs are getting approved, revenues are going down, margins are going to go down."

Scientists proceed in their work by discovering a correlation and then picking apart the underlying mechanisms to find out why the correlation exists. In the field of aging research a great many as yet unexplained correlations exist, any one of which may point the way to important new knowledge. Take this for example: "Biological rhythms that oscillate with periods close to 24 h (circadian cycles) are pervasive features of mammalian physiology, facilitating entrainment to the 24 h cycle generated by the rotation of the Earth. In the absence of environmental time cues, circadian rhythms default to their endogenous period called tau, or the free-running period. This sustained circadian rhythmicity in constant conditions has been reported across the animal kingdom, a ubiquity that could imply that innate rhythmicity confers an adaptive advantage. In this study, we found that the deviation of tau from 24 h was inversely related to the lifespan in laboratory mouse strains, and in other rodent and primate species. These findings support the hypothesis that misalignment of endogenous rhythms and 24 h environmental cycles may be associated with a physiological cost that has an effect on longevity."

Via EurekAlert!: "Adoptive immunotherapy is targeted to situations when the immune system fails to detect a disease [such as cancer]. The adoptive immunotherapy strategy is to harvest T cells from the patient, engineer them to spot the disease and then send them back in, like police detectives with a reliable tip. A major drawback, however, has been that the T cells still need to call for back-up forces from a variety of other cell types in the body, but they can't. They die out quickly without doing enough good. The new approach is to further engineer the T cells to be able to support themselves rather than relying on other immune cells [and] to insert the ability to switch that self-support on or off, to ensure that they don't grow out of control. That way, the T cells can persist in fighting the disease without becoming a cancer themselves. ... This is an integration of a cell-based therapy application with new synthetic biology tools that have come up from foundational research. ... Generally, the results showed that their engineering produced healthier, faster-growing populations of the T cells, until the drugs were withdrawn and growth shut down. In the human cell cultures, for example, the technology led to a 24 percent increase in the live T-cell population compared to controls and 50 percent fewer cells dying off."

From MSNBC: "Four common bad habits combined - smoking, drinking too much, inactivity and poor diet - can age you by 12 years, sobering new research suggests. The findings are from a study that tracked nearly 5,000 British adults for 20 years, and they highlight yet another reason to adopt a healthier lifestyle. Overall, 314 people studied had all four unhealthy behaviors. Among them, 91 died during the study, or 29 percent. Among the 387 healthiest people with none of the four habits, only 32 died, or about 8 percent. ... The risky behaviors were: smoking tobacco; downing more than three alcoholic drinks per day for men and more than two daily for women; getting less than two hours of physical activity per week; and eating fruits and vegetables fewer than three times daily. These habits combined substantially increased the risk of death and made people who engaged in them seem 12 years older than people in the healthiest group ... The findings don't mean that everyone who maintains a healthy lifestyle will live longer than those who don't, but it will increase the odds." This study joins many others in putting a number on the harm we do to ourselves by failing to keep up with the health basics.

This paper outlines the overlap between the ways in which both processes of aging and eating too much lead to the loss of muscle mass and strength: "Sarcopenia, which is defined by the loss of skeletal muscle mass, predisposes skeletal muscle to metabolic dysfunction which can precipitate metabolic disease. Similarly, overnutrition, which is a major health problem in modern society, also causes metabolic dysfunction in skeletal muscle and predisposition to metabolic disease. It is now the prevailing view that both aging and overnutrition negatively impact skeletal muscle metabolic homeostasis through deleterious effects on the mitochondria. Accordingly, interplay between the molecular pathways implicated in aging and overnutrition that induce mitochondrial dysfunction are apparent. Recent work from our laboratory has uncovered the stress-responsive mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) as a new player in the regulation of metabolic homeostasis in skeletal muscle and mitochondrial dysfunction caused by overnutrition. These observations raise the intriguing possibility that MKP-1 may function as a common target in the convergence between sarcopenia and overnutrition in a pathophysiological pathway that leads to a loss of skeletal muscle mitochondrial function." Going the other way, you might recall that calorie restriction helps to maintain muscle mass with age.

Nature looks at the chaotic state of bringing cancer vaccines to trial: "Many first-generation cancer vaccines such as PANVAC, a pancreatic cancer vaccine, were deemed safe but failed to demonstrate that they significantly slowed the progression of cancer. Because cancer-associated antigens - such as those used in Provenge - are also found at low levels in healthy tissue, their ability to trigger a powerful immune response may be blunted. A second generation of vaccines, designed to provoke a stronger immune response, is under development, with some scientists now focusing on antigens that are found only on tumour cells. ... Over the past decade, researchers have reached a deeper understanding of how tumours actively suppress immune responses in their immediate environment, which can dampen responses to cancer vaccines. To overcome this, some therapies currently in development combine the vaccine with chemotherapies that are designed to counteract this immune suppression. ... For some in the field, the struggle to create effective cancer vaccines conjures up memories of the long battle to develop antibody-based therapies, which are now a mainstay of the biotechnology industry. There, too, a series of clinical-trial failures initially soured the field's reputation ... We realized you just have to test a lot of drugs to find one that works, and it's the same for a cancer vaccine."



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