Longevity Meme Newsletter, November 03 2008

November 03 2008

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.



- Appropriate Responses To Risk
- Looking Far Ahead
- An Introduction to IGF-1 and Insulin
- Discussion
- Latest Healthy Life Extension Headlines


Why is it that most people do very little to address the greatest risk they face of suffering harm to life and health?


"The rational actor looks at risks to life and health ahead and acts to minimize those risks. Since we all have limited time and resources, we have to prioritize: we make lists, in our heads if nowhere else, putting the most likely and terrible outcomes up at the top. Highly unlikely but terrible outcomes don't receive much attention: meteors, lightning strikes, that sort of thing. Likely but merely unpleasant events might just be suffered as a cost of getting on with life: catching the flu is an obnoxious happenstance, but not particularly threatening for most of us. There are more important things to worry about while buying insurance and otherwise taking care of essentials.

"So you end up with a list involving fires, car accidents, sudden implosion of the company you work for, that sort of thing. In that, most of us are not being terribly rational, as aging isn't on the list. It is absolutely going to happen, and it leads to the most terrible personal consequence possible - death - via numerous other very nasty personal consequences. Alzheimer's, heart disease, cancer, and all the rest. We all have a 100% chance of aging as things stand, and it's the worst thing that will happen to most of us. So why isn't it up near the top of that priority list?"


The 2030s will be the dawn of an era of advanced nanotechnology, building upon the results of the biotechnology revolution presently in full swing. Computers will be ten thousand times more powerful, and our knowledge of human biochemistry far greater than at present. Most importantly for the long term, significant inroads will be made into reverse engineering the brain - and thus laying the groundwork for replacing our fragile neural tissues with more durable and flexible nanomachinery. Scientists know enough now to sketch the boundaries of that research and development process:


"The Future of Humanity Institute has published a (PDF) roadmap to whole brain emulation (WBE) - a tiny step towards the visions outlined above. In intent it could be compared to SENS, or the work of Drexler, Freitas and others on the design of medical nanomachinery: a foundation of theory on which research strategies can be built. ... There do not appear to exist any obstacles to attempting to emulate an invertebrate organism today. We are still largely ignorant of the networks that make up the brains of even modestly complex organisms. Obtaining detailed anatomical information of a small brain appears entirely feasible and useful to neuroscience, and would be a critical first step towards WBE. Such a project would serve as both a proof of concept and test bed for further development."


A great deal of research is focused on the mechanisms of metabolism associated with IGF-1 and insulin, as this seems to a central link between the operation of metabolism and consequent effects on life span. Here's an introduction:


"I imagine that a decade from now researchers will fully understand how IGF-1, insulin, growth hormone, and calorie restriction all fit together into the bigger picture of the natural range of metabolic processes in response to circumstances. Your diet and exercise choices change the way your biochemistry operates: the biochemical mechanisms by which this happens have a deep evolutionary history."


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!




To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

Unregulated Prices Fall, While Quality Improves (October 31 2008)
A piece from the LEF Magazine that makes the points about modern medical research that most people don't think about: "the public today tolerates federal and state laws that enable pharmaceutical companies to conduct business as a virtual monopoly. The result is that Americans pay outlandish prices for mediocre drugs that are often laden with side effects. ... Unlike regulated prescription drugs, the cost of dietary supplements has plummeted over the past three decades. ... in a free market environment, technological breakthroughs that occurred in telecommunications will also happen in medicine. ... More frightening is the suffocating effect that regulation has on the discovery of life-saving therapies. Just imagine if advancement in clinical medicine progressed at the same rapid rate as telecommunications. If it did, we would probably have cures for most killer diseases today!" Heavily regulated markets are bloated, slow markets, in which the incentives are so set as to discourage progress. Present regulation is a very real threat to the future of your health and longevity.

Incremental Improvements in Stem Cell Therapy (October 31 2008)
Researchers continue to find ways to alter stem cells to produce better therapies: "Adult stem cells resemble couch potatoes if they hang out and divide in a dish for too long. They get fat and lose key surface proteins, which interferes with their movement and reduces their therapeutic potential. Now, via a simple chemical procedure, researchers have found a way to get these cells off the couch and over to their therapeutic target. To do this, they simply added a molecule called SLeX to the surface of the cells. The procedure took just 45 minutes and restored an important biological function. ... Delivery remains one of the biggest hurdles to stem cell therapy. The blood stream offers a natural delivery vehicle, but stem cells don't move through blood vessels normally after being expanded in culture. Our procedure promises to overcome this obstacle. ... Karp cautions that his lab's discovery must be validated in animals, before doctors can apply it in the clinic. He's collaborating with another lab to test the homing ability of the SLeX-dotted cells in mice."

A Little More on IGF-1 and Growth Hormone (October 30 2008)
Following up on a recent Fight Aging! post, more on the role of IGF-1 in longevity: "Using a mouse model relevant for humans, we showed that lifespan can be significantly extended by reducing the signaling selectively of a protein called IGF-I in the central nervous system. ... This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. ... continuously low IGF-I and low growth hormone levels favor extended lifespan and postpone age-related mortality. ... our results further challenge the view that administration of GH can prevent, or even counteract human aging. This knowledge is important since growth hormone is often prescribed to elderly people in an attempt to compensate the unwanted effects of aging."

Ouroboros On Mitochondrial Uncouplers (October 30 2008)
From Ouroboros: researchers "suggest that mitochondrial uncoupling is an effective mimic of [calorie restriction (CR)]. In mitochondria, the electron transport chain uses electrons from glucose and lipids to pump protons across a membrane. This proton gradient can be used to make energy in the form of ATP through oxidative phosphorylation. The process is kind of like generating hydropower. Uncouplers work by putting a leak in the dam, which lets water through without going to the generator. They 'uncouple' the electron transport chain from oxidative phosphorylation, thus reducing the efficiency of energy production. Although animals have uncoupling proteins (these proteins are important for thermogenesis, especially during hibernation), so far there are no known agonists. The researchers instead used low doses of the mitochondria uncoupler DNP. ... The DNP treated mice ate the same amount of food as control mice but had lower body mass [and] showed many phenotypes observed in calorie restricted mice. Like CR mice, DNP treated mice had higher rates of respiration with lower production of ROS. ... Most importantly, DNP treated mice showed an extended lifespan. This study suggests that mitochondrial uncouplers are an effective mimic of calorie restriction and might be a realistic therapeutic intervention for delaying aging and extending lifespan."

Your Internal Antioxidant Systems (October 29 2008)
While consuming antioxidants doesn't seem to do much good, the state of your internal antioxidant systems is very important to health and longevity. "In aerobic organisms, oxygen is essential for efficient energy production but paradoxically, produces chronic toxic stress in cells. Diverse protective systems must exist to enable adaptation to oxidative environments. Oxidative stress (OS) results when production of reactive oxidative species (ROS) exceeds the capacity of cellular antioxidant defenses to remove these toxic species. Epidemiological and clinical studies have linked environmental factors such as diet and lifestyle to cancer, diabetes, atherosclerosis, and neurodegenerative disorders. All of these conditions, as well as the aging process, are associated with OS due to elevation of ROS or insufficient ROS detoxification." You might recall that enhancing or replicating the effect of these internal systems has successfully extended mouse life spans.

Complexities of Immune System Decline (October 29 2008)
The decline of immune system function with age varies in degree from person to person. Here is one reason why some older folk suffer less than others. Perhaps there's something that can be done with this knowledge as researchers become more capable in cell manipulation: "the number of peripheral naive T-cells declines throughout life and they exhibit severe functional defects at advanced age. However, we have recently identified a non-regulatory CD8+CD45RO+ CD25+ T-cell subset that occurs in a subgroup of healthy elderly individuals, who still exhibit an intact humoral immune response following influenza vaccination. Here, we demonstrate that CD8+CD45RO+CD25+ T-cells share phenotypic and functional characteristics with naive CD8+CD45RA+CD28+ T-cells from young individuals, despite their expression of CD45RO. CD8+CD45RO+ CD25+ T-cells also have long telomeres and upon antigenic challenge, they efficiently expand in vitro and differentiate into functional effector cells. The expanded population also maintains a diverse T-cell receptor repertoire. In conclusion, CD8+CD45RO+CD25+ T-cells from elderly individuals compensate for the loss of functional naive T-cells and may therefore be used as a marker of immunological competence in old age."

Lipids and Alzheimer's (October 28 2008)
The brain is complex organ, and Alzheimer's is a complex disease: a wide range of strategies produce results that look promising while not addressing the root cause. Indeed, distinguishing symptoms from root causes in Alzheimer's is still an ongoing concern. Here is a potential strategy I have not seen mentioned before: "scientists working with laboratory mice have discovered that complete or partial removal of an enzyme that regulates fatty acid levels lessened the memory and learning deficits of Alzheimer's ... The most striking change we discovered in the Alzheimer mice was an increase in arachidonic acid and related metabolites in the hippocampus, a memory center that is affected early and severely by Alzheimer's disease ... an enzyme called group IVA phospholipase A2 (or PLA2) released arachidonic acid [in] the brain ... removal or even partial reduction of PLA2 prevented memory and learning deficits and other behavioural abnormalities in the Alzheimer mice." It is worth noting that PLA2 is upstream in biochemical signaling processes that lead to inflammation - I suspect this has more to do with inflammation than fatty acids per se.

Calorie Restriction Delays Mitochondrial Damage (October 28 2008)
Another win for the practice of calorie restriction: "According to the "mitochondrial theory of aging" the lifelong accumulation of various kinds of damage to mitochondrial DNA (mtDNA) has been related to the age-dependent mitochondrial bioenergetic dysfunction. Caloric restriction (CR) diet is able to prevent or delay the onset of several age-related damages to mtDNA. The effects of aging and CR on the presence of abasic sites and single-strand breaks of the sugar-phosphate backbone in mtDNA have been analyzed [in a] region of brain mtDNA from young and old ad libitum-fed and old CR-treated rats. The region [is] is highly damaged in the old ad libitum-fed animals with respect to the young ones, whereas in the CR rats it shows a much lower extent of damage. The data confirm, at single nucleotide resolution, the protective effect of CR on the age-related mtDNA damage." Damage to mitochondrial DNA appears to provide an important contribution to degenerative aging - we would expect this process to be slowed in calorie restriction, and here is confirmation.

The Immortality Trap (October 27 2008)
Too many discussions of radical life extension veer off into the immortality trap - at which point things degenerate into hair splitting and angels dancing on the head of a pin. Talking about immortality has little relevance to the practical objective of reversing degenerative aging in humans. Over at Depressed Metabolism you'll find an example of how this tends to progress, followed by these thoughts: "Although speculation about how immortality may affect human psychology can be intriguing, our limited knowledge about the universe and lack of empirical observations of actual immortals make this a highly speculative affair, leaving much room for injecting personal feelings and wishful thinking. ... Few philosophers against immortality argue that today's lifespan is too long. Which again raises the question, how long is too long? Ultimately, such an answer can only be answered empirically by the individuals who will live a much longer lifespan than those living today." It comes back to practical concerns in the end: I, for one, am in favor of getting the job done first and pontificating later, when there is all the time in the world to do so.

Screening For Longevity Drugs (October 27 2008)
From Ouroboros: "The observation that long-lived and relatively healthy animals can be obtained by simple genetic manipulation prompts the search for chemical compounds that have similar effects. Since aging is the most important risk factor for many socially and economically important diseases, the discovery of a wide range of chemical modulators of aging in model organisms could prompt new strategies for attacking age-related disease such as diabetes, cancer and neurodegenerative disorders ... Long-lived organisms tend to be resistant to many types of stress, whereas short-lived organisms tend to be stress sensitive. This happy coincidence allows us to screen for longevity mutants by looking for stress resistance rather than long life ... it's quite impressive that so many different antioxidants of so many different types can confer thermotolerance and increased longevity [in nematode worms], and suggests that perhaps the association between antioxidants and longevity may have never had much to do with oxidation as such, but rather with some as-yet-uncovered connection between antioxidants and the activation of stress response pathways."



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