Longevity Meme Newsletter, May 10 2010

May 10 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.



- Aubrey de Grey at the Lift10 Conference
- SENS Foundation is Looking for an Academic Coordinator
- Grow Fat and Suffer the Consequences
- A Conservative View of Exercise and Alzheimer's
- Discussion
- Latest Healthy Life Extension Headlines


Biomedical gerontologist and engineered longevity advocate Aubrey de Grey spoke at the Lift10 conference in Geneva this past weekend:


"The questions people invariably ask de Gray focus on such mundane matters as where all these extra people will live, how pension plans will pay for them and what they'll do with their time, but he says the questions are not the right ones. We should balance out these against the problems caused right now by '100,000 people a day getting very sick and staying that way a long time and then dying.'"


Amongst its other projects, the SENS Foundation runs an academic outreach initiative which allows life science students to work on projects important to the repair of aging, such as isolating bacterial enzymes capable of breaking down damaging aggregates that build up in the body with aging. The most recent program coordinator has moved on to work at a cancer immunotherapy startup, and so the Foundation is looking for a new hire:



Excess fat tissue and the lifestyle required to obtain it have long-term and significant consequences in terms of your health and life expectancy:


"Increasing urbanization, aging populations, obesity, and falling levels of physical activity are all contributing to the rise of type 2 diabetes worldwide. The main cause is the growing prevalence of obesity, in Europe and in Latin America. In North America obesity is considered to be responsible for 90% of type 2 diabetes in females. Male obesity is associated with type 2 diabetes slightly less, at 70-80% in the European Union and in the US. ... Thin, healthy people aren't thin and healthy because they have magic genes. They're thin and healthy because they are eating less and exercising more than the fat folk. This isn't rocket science, and it does have an impact on the bottom line of your life expectancy."


Regular exercise makes everything better:


"The benefits [of exercise] tend to be on the order of a 20 to 30 percent reduction in being diagnosed with Alzheimer's disease and other such diseases. And again, this isn't universal but this is found in an increasing number of studies. ... There are improvements in the chemistry of the brain in terms of the molecules that protect the brain, increases in the number of connections between neurons, which allows us to encode new learning and memory, and even the birth of new neurons in one region of the brain that supports memory."

Bear in mind that Alzheimer's has many similarities with type 2 diabetes, in terms of its risk factors and even aspects of its biochemistry:



The highlights and headlines from the past week follow below.

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A number of past studies have shown improvement in Parkinson's disease with stem cell transplants. Here is another: "Endometrial stem cells injected into the brains of mice with a laboratory-induced form of Parkinson's disease appeared to take over the functioning of brain cells eradicated by the disease. The finding raises the possibility that women with Parkinson's disease could serve as their own stem cell donors. Similarly, because endometrial stem cells are readily available and easy to collect, banks of endometrial stem cells could be stored for men and women with Parkinson's disease. ... In the current study, the researchers generated stem cells using endometrial tissue obtained from nine women who did not have Parkinson's disease and verified that, in laboratory cultures, the unspecialized endometrial stem cells could be transformed into dopamine-producing nerve cells like those in the brain. The researchers also demonstrated that, when injected directly into the brains of mice with a Parkinson's-like condition, endometrial stem cells would develop into dopamine-producing cells. ... stem cells derived from endometrial tissue appear to be less likely to be rejected than are stem cells from other sources."

From the New Scientist: "when young mice are learning, a molecular fragment known as an acetyl group binds to a particular point on the histone protein that DNA wraps itself around - with the result that the cluster of learning and memory genes on the surrounding DNA ends up close to the acetyl group. ... This acetyl "cap" was missing in the older mice that had been set the same tasks. From this, the team concludes that the cap acts as an "on" switch for the cluster of learning and memory genes: removing the cap switches off the genes. Next, by injecting an enzyme known to encourage caps to bind to any kind of histone molecule, [researchers] artificially flipped the switch to the on position in old mice. The acetyl group returned to the histone molecule and the mice's learning and memory performance became similar to that of 3-month-old mice. ... it is still not clear why the switch flips off as we get older. One possibility is that it might help us cope with other cellular assaults that come with ageing, such as oxidative stress, [which] would mean that switching it on might have damaging side effects."

An interesting example of how immune therapies can eliminate or reduce some of the ways in which the aging body damages itself: "Cholesterol is transported in the blood in LDL particles, which are a kind of fat drops that can accumulate in the walls of blood vessels. LDL activates the immune defence and triggers an inflammation in the blood vessels that leads to atherosclerosis (also known as arteriosclerosis). When the atherosclerotic plaque finally ruptures, a blood clot is formed that in turn can cause a heart attack or stroke. It was previously thought that the inflammation in the blood vessels arises when the T cells react to oxidised LDL particles located in the atherosclerotic plaque. Now, however, [researchers have found] that the opposite is true, namely that the T cells react to components in the normal LDL particles, and that they no longer recognise LDL once it has been oxidised. ... Since reactions to LDL can be dangerous, T cells are normally held in check by inhibitory signals. The body's own control works well as long as the LDL keeps to the blood, liver and lymph glands. But when it accumulates in the artery wall, this inhibition is no longer enough, the T cells are activated and an inflammation arises. ... Vaccination against the receptor that the T cells use to recognise LDL can block the immune reaction and reduce the disease by between 60 and 70 per cent."

Viruses can be used as a form of targeted anti-cancer therapy, and human trials are soon set to start: "Particular parvoviruses normally infect rodents, but they are also infectious for human cells. However, they do not cause any disease symptoms in humans. Most importantly, these viruses have an astonishing property: They kill infected tumors cells without causing any damage to healthy tissue. ... Many different viruses have been tested before in cancer therapy, particularly for treating those types of cancer for which there are no effective established treatment methods. The [researchers] realized early on that parvovirus H-1 has important advantages over other viruses. Now they have been the first to prove that malignant glioblastomas regress completely as a result of treatment with these viruses. ... Parvoviruses pass the blood brain barrier so that they can be administered via the blood stream. In addition, they reproduce in cancer cells, which is particularly important for successful treatment of glioblastoma with its diffuse growth. Thus, the second generation viruses reach and eliminate even those cancer cells that have already settled at some distance from the primary tumor. ... researchers [expect] to be able to admit the first patients to the trial by the end of the year."

From EurekAlert!: "The muscles of elderly people and of people with type 2 diabetes contain lower concentrations of a protein known as PARL (short for 'presenilin-associated rhomboid-like'). PARL plays an important role within cells in remodeling power-generating mitochondria. It's PARL's job to oversee mitochondria's quality control, specifically by maintaining their integrity as the cellular components undergo normal processes of fission and fusion. The findings provide yet another link between insulin resistance and the function of mitochondria. ... When mitochondria aren't functioning properly, food doesn't get metabolized to the level that it should ... Instead of getting burned, fats accumulate in cells where they impair insulin's action. As mitochondria fail to work efficiently, they also produce more damaging free radicals. ... Relative to younger people, older people showed signs of insulin resistance. They also had fewer numbers of mitochondria and lower expression of the PARL gene. ... We hypothesize that impaired PARL function is an important risk factor for the development of insulin resistance in skeletal muscle by decreasing mitochondrial mass and energetics and increasing oxidative stress, thus contributing to impaired glucose metabolism. As insulin resistance continues to develop, mitochondrial function, oxidative damage, and PARL activity may decline further, leading to a vicious cycle that eventually contributes to the development of [diabetes] or other age-associated diseases, including sarcopenia."

The Seattle Times notes recent research: "A new study finds that calorie restriction may bolster the immune system in adults. Researchers [randomly] placed 46 overweight, but not obese, men and women age 20 to 40 on one of two diets for six months: one in which calories were reduced 10 percent, and another in which they were reduced 30 percent. All food was supplied to the test subjects. The participants were tested to see what effect calorie restriction had on their immune system. They were given a delayed-type hypersensitivity test, which can detect allergens, among other things, and is considered a way to check whole-body immune response. Researchers also checked T-cells, a kind of white blood cell, and another immune system marker. At the end of the six months, [delayed type hypersensitivity] response went up in both the 10 percent and the 30 percent calorie-restricted groups compared with the beginning of the study. Both groups also showed improvement in T-cell function."

From the SENS Foundation: "Progress toward the goal of tissue rejuvenation via stem cells and tissue engineering ("RepleniSENS") is badly hampered by the surprising fragility of human embryonic stem cells (hESC) relative to mouse ESC (mESC). Unlike their murine counterparts, hESC undergo extensive cell death following enzymatic single-cell dissociation; as a result, researchers are forced to rely on laborious mechanical microdissection, or on narrowly-control enzymatic dissociation that ensures that hESC remain above a minimum cluster size. These requirements make their expansion extremely tedious and inefficient. The reasons for the intolerance of hESC to full dissociation - and the development of means to ameliorate it - are therefore of considerable biomedical as well as scientific interest. This month, researchers [report] that they have at once apparently provided the detailed molecular basis for this frustrating anomaly, and its abrogation using either modified culture protocols or either of two small molecules. ... Injected into an area that already enjoys a high level of government and industry investment, these tools bring us closer to realizing the promise of cell therapies and tissue engineering for the treatment of a range of age-related and traumatic diseases and disorders, as well as for the rejuvenation of aging tissues."

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."

From the SENS Foundation: "To date, the dominant therapeutic strategy for both specific age-related diseases and (to the extent that it has been contemplated) the degenerative biological aging process itself, has been based on altering metabolic pathways. Biomedical research has centered on the detailed understanding of pathways seen to be contributing to disease etiology or pathogenesis, and the identification of putatively dysfunctional components hormones, receptors, enzymes, cytokines, etc), which are then targeted for manipulation by small molecules or other means in hopes of normalizing function and thereby alleviating symptoms or slowing progression of pathology. ... there is a critical flaw in the unconsciously-drawn analogy between its use in the development of therapies to manage specific diseases, and its potential for the treatment of the degenerative aging process. Unlike most non-communicative diseases, degenerative aging is not the result of the dysfunction of metabolic pathways, but of the the undesirable long-term side-effects of their normative biochemistry. Put another way: biological aging is the pathological result of perfectly-functioning, [healthy] metabolic processes. ... Thus, transposing the conventional drug-development pathway onto the aging process necessarily entails interfering with the normal metabolism - and doing on an indefinite basis, from the day that a 'patient' first begins therapy until his or her death. But of course, those same pathways evolved to ensure survival and fitness, and their existence and the normal mode of regulation are the very basis of ordinary health and function. We interfere with the intrinsic operation of such pathways at our peril."

A detailed examination of recent progress from the SENS Foundation: "Recent years have seen both substantial progress, and significant frustration, in the preferred regenerative engineering approach to the treatment and prevention of Alzheimer's disease (AD), and the eventual regeneration of genuinely youthful cognitive function: immunotherapeutic clearance of beta-amyloid (AmyloSENS). ... results appear to many to commend an earlier window of opportunity for intervention, before concomitant [damage] and neuronal losses have made the removal of beta-amyloid alone insufficient for cognitive rescue. Early intervention might also maximize the therapeutic window for vaccination, preventing the burden of beta-amyloid neuropathology from ever reaching levels so high as to interact with other forms of aging damage in already frail and immunosenescent people." Present work on immune therapies for clearing unwanted biochemical junk from the body looks promising - there is every sign that today's advances will broaden into a general technology platform for this purpose. Researchers will be able to develop therapies that can be applied incrementally throughout life to remove the age-related gunk like beta-amyloid before it rises to dangerous levels.



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