LONGEVITY MEME NEWSLETTER
November 29th 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.
- Exercise and the Age-Damaged Immune System
- Is Nuclear DNA Damage a Cause of Aging?
- On Insulin Metabolism and Aging
- Latest Headlines from Fight Aging!
EXERCISE AND THE AGE-DAMAGED IMMUNE SYSTEM
Regular exercise, along with calorie restriction, is the most effective presently available tool you can use to improve your odds of living a longer, healthy life. No present medical technology can do as much - which is a situation we'd all like to change. A recent Fight Aging! post looks at one of the ways in which exercise can help:
"You might recall that one of the primary issues with our immune systems is that necessary cells become crowded out over time - the body supports only so many immune cells, and the naive T cells needed to fight new invaders become depleted in favor of memory cells uselessly devoted to persistent viruses that the body cannot clear. In essence, the adaptive immune system is evolved to hit the ground running and fight the battles of a young life - and that front-loading of its effectiveness leaves us high and dry later on, once too many battles have been fought.
"One of the strategies that medical researchers could use to solve this problem is to destroy the unwanted specialist cells, freeing up room for more useful T cells and restoring immune response to a more youthful level. The targeted cell-hunting and cell-killing technologies under development in the cancer research community would be ideal for this use.
"Now consider that even though the vast majority of people are infected with persistent viruses like cytomegalovirus, the quality of their immune systems in later life varies widely. Some people have comparatively good immunity when they are old - nowhere near as good as when young, but certainly better than their fellows. It could be argued that exercise goes some way towards establishing this difference - and in this paper, the argument is that exercise lures out decrepit T cells so that they can be destroyed by the body's maintenance systems."
IS NUCLEAR DNA DAMAGE A CAUSE OF AGING?
When most people say "DNA," they mean the DNA that resides in the nucleus of every cell. Despite an amazing array of highly efficient repair mechanisms, this nuclear DNA accumulates damage over time. Is this a process that contributes to degenerative aging?
"It is well settled that the level of nuclear DNA damage and mutation exhibited by an organism rises over time. It is also well settled that higher levels of nuclear DNA damage and mutation mean a greater cancer risk - this is one of the reasons why cancer is predominantly a disease of the old. The more cells that suffer DNA damage, the more likely it is that one or more cells experience exactly the type of damage needed to run amok as the self-replicating seeds to a cancer. But is nuclear DNA damage and mutation a cause of aging?
"That increasing instability of the genome contributes to age-related degeneration is the present working assumption for much of the aging research community, but this hypothesis is not unchallenged. The lack of a definitive proof is one problem: there is no good experiment to show that reduction in nuclear DNA damage levels - and only nuclear DNA damage levels - extends life. We can point to, for example, the fact that calorie restriction results in lower nuclear DNA damage levels, but this is only correlation. Calorie restriction slows the progression of every measure of biological aging, and produces significant changes in all of the master controls of metabolism and their subsystems, which makes it very hard to tease out any one dominant first cause."
ON INSULIN METABOLISM AND AGING
You'll find a pair of posts on the link between insulin metabolism, related controlling mechanisms in our biology, and aging at Fight Aging!:
"It is an unfortunate fact of life that some people are dealt a better hand by chance and happenstance. This includes the biology we are born with, and its contributions to our life expectancy: for example, some people have better mitochondrial DNA than others, which does seem to be correlated with inherited longevity. By way of a different example, let me point out recent research that shows a correlation between better insulin metabolism and inherited longevity. "
"As a companion to yesterday's post on insulin metabolism and human longevity, here is an open access paper that looks at stem cells, insulin signaling processes, and aging. In short, the activity of stem cells is vital to your long-term health, but this activity declines with age - and this decline is linked to other age-related changes, such as in insulin metabolism."
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!
LATEST HEADLINES FROM FIGHT AGING!
IMPLICATING CELLULAR SENESCENCE AS ONE CAUSE OF AGING
Friday, November 26, 2010
A recent open access review paper looks at the evidence for accumulated senescent cells as one of the causes of aging: "Epidemiological studies have shown that age is the chief risk factor for lifestyle-related diseases such as cardiovascular disease and diabetes, but the molecular mechanisms that underlie the increase in the risk of such diseases conferred by aging remain unclear. ... Interestingly, most of the molecules that influence the phenotypic changes of aging also regulate cellular senescence, suggesting a causative link between cellular senescence and aging. ... Cell division is essential for the survival of multicellular organisms that contain renewable tissues, but places the organism at risk of developing cancer. Thus, complex organisms have evolved at least two cellular mechanisms to prevent [cancer]: apoptosis and cellular senescence. In this regard, aging and age-associated diseases can be viewed as byproducts of the tumor suppressor mechanism known as cellular senescence. Consistent with this idea, the number of senescent fibroblasts increases exponentially in the skin of aging primates. Conversely, extension of the lifespan by calorie restriction decreases biomarkers of cellular senescence."
LONG-LIVED SPECIES AND AGING
Friday, November 26, 2010
From Maria Konovalenko: "There are many studies that involve extending the lives of laboratory animals - through gene manipulation, pharmaceutical intervention, and dietary restriction. But according to Steven Austad, a biologist at the Barshop Institute for Longevity and Aging Studies, these manipulations 'pale in comparison to the remarkable diversity of lifespan produced by evolution.' He points out that maximum life span across the animal kingdom varies 40,000-fold. For example, some adult flies live less than an hour; some shellfish for centuries. Among mammals alone, longevity varies 1,000-fold. The average fruit fly lives a little more than a month, so scientists' ability to double its lifespan is a remarkable achievement but Austad says we may be missing something by focusing so much of our longevity research on animals - flies, worms, mice - that are 'demonstrably unsuccessful at combating basic aging processes.' He suggests we put more effort into understanding molecular solutions nature has devised to help long-living creatures evade their deaths. ... Aging affects all of us. People are going to continue to live longer because of medical advances. We want them to live healthier as well as live longer. The best way to achieve longer health is to figure out ways to medically slow aging. That's a different sort of approach than figuring out how to cure cancer or heart disease. If you can cure aging, or if you can slow it, then you can really delay or prevent a whole host of disabilities and diseases."
THE FDA MUST GO
Thursday, November 25, 2010
From the Huffington Post: "There is no question that social equity issues such as poverty and access to medical treatment affect life expectancy. The same is true with our life style choices (e.g., eating, exercise). Yet the precise benefit often is elusive as is the case for alcohol where epidemiological studies find surprisingly contradictory results. So, what happens when we throw [the] FDA into the brew? We have a system of FDA approval that requires a pharmaceutical company show three things: (1) a mechanism of action (i.e., identify why a drug works), (2) safety and (3) efficacy in managing a measurable biologic end point associated with a disease. This last condition is a problem. Look at the conundrum: You're a researcher and you walk into FDA one day and say: 'I have in this bottle an elixir that if taken every day of your life will add on average 4 years to how long you can expect to live.' FDA says: 'What disease will it cure?' The researcher says: 'It won't cure disease, it will postpone or mitigate the lethality of some diseases, but as you get older you will get other diseases.' FDA then hopefully says: 'We get it. While we do not now nor have we ever thought about age as a disease metric, we accept the concept. All we need to do is test your drug on a sufficiently large population and for a long enough period of time to prove to us it works.' That is the problem." For so long as the FDA and its more similar foreign counterparts exist, progress in turning science into applied longevity-enhancing therapies will be greatly slowed.
ALCOR RECEIVES $7 MILLION BEQUEST
Thursday, November 25, 2010
Good news for the cryonics community: "Alcor has received seven million dollars following final settlement of the estate of a confidential member who was cryopreserved several years ago. The bequest will be divided equally between Alcorâ€™s Patient Care Trust and a new Endowment Fund to be created with a maximum legally allowed annual distribution of 2% per year. This will double the value of the Patient Care Trust to approximately $7 million, increasing the security of all 100 patients in Alcorâ€™s care. The Patient Care Trust is devoted solely to funding the ongoing biostasis of Alcor's patients and their eventual revival and reintegration into society when the medical technology to restore them to full health is developed. ... This is a marked departure from past Alcor practice, which has been to place windfalls into either the Alcor general or reserve fund accounts. The funds would then be gradually depleted to cover operating deficits, with the hope that an additional windfall would arrive prior to the depletion of funds. Alcor is instead now seeking to eliminate structural operating deficits so that it is no longer dependent upon these unpredictable events. Consequently, this bequest will not make a large difference in Alcorâ€™s budget next year: it will only contribute an extra $70,000. While $70,000 will help close next yearâ€™s deficit, it must be combined with other difficult measures. In the longer term, however, this financial discipline will make Alcor a healthier and more robust organization."
STEM CELLS VERSUS LIMB ISCHEMIA
Wednesday, November 24, 2010
Early efforts to simply transplant stem cells and let them do their work continue to show promise. First generation cell transplants are not a miracle cure, but they are an improvement over any other options available for some patients: "researchers are [utilizing] patients' own stem cells to regenerate heart and vascular tissue [in] a study examining stem cell transplantation as treatment for critical limb ischemia. ... Traditionally, cardiovascular medicine has focused on repairing damaged tissues with medication or surgery. For some patients, their cardiovascular disease is advanced to the point that standard treatment options are not effective. Regenerative cardiovascular medicine strives to redevelop cardiac and vascular tissue and stimulate new blood supply to areas like the heart and legs by using stem cells already present in the patient's body. ... [the] study examined the effectiveness of stem cell therapy in limb preservation for patients with critical limb ischemia (CLI). CLI develops in patients with severe obstruction of the arteries which limits blood flow to the extremities. CLI results in more than 100,000 amputations annually in the United States. The trial tested the ability of CD34+ cells to stimulate new blood vessel formation in ischemic limbs, which can improve perfusion and salvage function. ... The patients enrolled in this study were [in] the later stages of peripheral artery disease and at heightened risk for amputation. Patients in the randomized group had CD34 injected at eight locations in the ischemic limb and were followed for 12 months. ... Stem cell treatment was associated with a significant reduction in amputation rate. Treatment was associated with a 50 percent reduction in the total amputation rate compared to control."
THE 15TH ANNUAL LONGEVITY PRIZE
Wednesday, November 24, 2010
The Longevity prize offered by La Fondation IPSEN is a modest cash award and recognition given to leading researchers in the field of aging and longevity science: "The 15th annual Longevity Prize has been awarded to Judith Campisi (Buck Institute for Age Research, Novato, USA) in recognition of the work she has been carrying in the domain of Longevity, Senescence and Cancer, by an international jury ... Founded in 1996, the Longevity Prize of La Fondation Ipsen has been awarded to renowned specialists ... Judith Campisi received a PhD in Biochemistry from the State University of New York at Stony Brook, and postdoctoral training in the area of cell cycle regulation and cancer at the Dana-Farber Cancer Institute and Harvard Medical School. As an Assistant Professor at the Boston University Medical School, she became interested in the control of cellular senescence and its role in tumor suppression and aging. She left Boston to accept a Senior Scientist position at the Lawrence Berkeley National Laboratory in 1991; in 2002, established a second laboratory at the Buck Institute for Age Research, where she is a Professor. At both institutions, she established a broad program to understand various aspects of aging, with an emphasis on the interface between cancer and aging. Campisiâ€™s laboratory has made several pioneering discoveries in these areas, and her research continues to challenge and alter existing paradigms."
THE NEED FOR A PARADIGM SHIFT IN MEDICAL RESEARCH
Tuesday, November 23, 2010
Maria Konovalenko considers the present day mainstream of medical science: "Considering the success of the moon race, why isnâ€™t there a comparable race against aging and its terrible diseases? Why is there so much opposition to promising developments such as therapeutic cloning or stem cell research? Why is modern medicine, and society at large, investing so much in trying to extend the last years of life (often spent in a nursing home) instead of trying to extend the period of youthful vigor? Mainstream medicine [operates] from the mortalist paradigm: it assumes that aging is 'normal' and nothing can be done about it. Weight gain, hearing and vision loss, a rise in blood pressure, a decline in muscle mass - all these are regarded as normal manifestations of aging. Since aging is not regarded as a disease, much less the most important disease, it is acceptable to treat only the symptoms of this universal, underlying degenerative syndrome. It is OK to treat heart disease or Alzheimer's, but not OK to try to slow the aging process itself, much less aim at physiological rejuvenation - even though this would be the most cost-effective solution to the catastrophic rise in medical costs as the population ages. We think medicine badly needs a paradigm shift."
MICROTHREADS AND MUSCLES
Tuesday, November 23, 2010
From the Technology Review: "Researchers have repaired large muscle wounds in mice by growing and implanting 'microthreads' coated with human muscle cells. The microthreads - made out of the same material that triggers the formation of blood clots - seem to help the cells grow in the proper orientation, which is vital for rebuilding working muscle tissue. ... We hypothesize that cells migrate along these scaffolds, which act like a conduit. The cells grow into the space where muscle used to be, but they grow in a guided way. Currently, there's not much doctors can do when someone suffers massive injury to a muscle, such as in a car crash or an explosion. Thick bands of scar tissue can form in the wound, leaving the muscle severely and permanently impaired. Scientists are developing numerous approaches to creating replacement muscle, including growing patches of cells in a dish, injecting stem cells into damaged muscle, and implanting cell-seeded scaffolds designed to mimic native tissue. While all of these efforts show promise for certain applications, one of the major challenges has been growing enough cells in the correct structure to heal large muscle wounds. ... Muscle alignment is very important. You want the sarcomeres [the basic functional unit of muscle] to be aligned, that's how you get muscle contractions."
KILLING CANCER WITH AN IMMUNE SYSTEM REBOOT AND ALTERED T CELLS
Monday, November 22, 2010
From EurekAlert!: "A potent anti-tumor gene introduced into mice with metastatic melanoma has resulted in permanent immune reconfiguration and produced a complete remission of their cancer. ... researchers used a modified lentivirus to introduce a potent anti-melanoma T cell receptor gene into the hematopoietic stem cells of mice. Hematopoietic stem cells are the bone marrow cells that produce all blood and immune system cells. The T cell gene, which recognizes a specific protein found on the surface of melanoma, was isolated and cloned from a patient with melanoma. The gene-modified stems cells were then transplanted back into hosts and found to eradicate metastatic melanoma for the lifetime of the mice. ... We found that the transplantation of gene-modified hematopoietic stem cells results in a new host immune system and the complete elimination of tumor. To date, cancer immunotherapies have been hampered by limited and diminishing immune responses over time. We believe this type of translational model opens new doors for patients with melanoma and potentially other cancers by taking advantage of the potent regenerative capacity of hematopoietic stem cells and new advances in gene therapy."
CALORIE RESTRICTION DELAYS AGE-RELATED HEARING LOSS
Monday, November 22, 2010
The practice of calorie restriction slows almost all aspects of aging examined to date: "researchers described experiments with mice showing that a 25% reduction in calories activated a single enzyme, Sirt3, that helped preserve hearing. Although small numbers of people practice strict caloric restriction - consuming just 1,000 to 1,500 calories a day - scientists concede that such a diet is exceedingly difficult. But there may be other ways to achieve the same benefits. ... If we can find compounds that activate Sirt3, we may be able to obtain some of the benefits of caloric restriction without having to restrict our calories. ... [researchers] carried out experiments with normal mice and mice without the Sirt3 enzyme. In one experiment both groups were fed the 25% reduced calorie diet for 10 months. The diet had the same weight loss effect on both groups. Although the diet delayed hearing loss at various frequencies in the normal mice, it did not work at all in the mice lacking Sirt3. ... What seems to happen that drives caloric restriction is that the organism senses it is under stress. There are then metabolic changes that favor self-preservation. ... Under normal conditions, he said, levels of Sirt3 are low. Caloric restriction appears to boost levels of Sirt3 and the boost helps the cells' energy factories, called mitochondria. The mitochondria make not only the energy, but also atoms called free radicals, which damage cells and advance the effects of aging. When Sirt3 levels rise, however, they reduce production of the harmful free radicals. One result is less damage to cells, including the cells of the inner ear."