Longevity Meme Newsletter, May 04 2009

May 04 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.



- Belaboring the Point on Exercise and Fat
- Update on the Science Against Aging Initiative
- Is "Life Extension" a Dead Term?
- Discussion
- Latest Healthy Life Extension Headlines


The value of avoiding excess fat and undertaking regular exercise can never be extolled often enough - though I suspect that everyone inclined to listen has already listened:


"We compared insulin sensitivity in seven younger endurance-trained athletes (YA), 12 older athletes (OA), 11 younger normal weight (YN), 10 older normal weight (ON), 15 younger obese (YO) and 15 older obese (OO) subjects using a glucose clamp. The non-athletes were sedentary.

"Insulin sensitivity was not different in YA vs. OA, in YN vs. ON or in YO vs. OO. Regardless of age, athletes were more insulin sensitive than normal weight sedentary subjects, who in turn were more insulin sensitive than obese subjects. Conclusions: Insulin resistance may not be characteristic of aging, but rather associated with obesity and physical inactivity."

For all that degenerative aging will remain inevitable until we develop repair biotechnologies like those envisioned in the Strategies for Engineered Negligible Senescence, many common age-related conditions are avoidable. Whether or not you will suffer them is - for most people - entirely a matter of the choices you make and the lifestyle you adopt.


The Russian group behind the Science Against Aging initiative has launched a new website and announced their scientific advisory board. It's Russian language only at the moment, but fortunately automated translation systems such as Google Translate are getting better:


The advisory board includes some familiar faces, such as Aubrey de Grey of the SENS Foundation, the Gavrilovs behind the reliability theory of aging and longevity, and Vladimir Skulachev, whose demonstrations of mitochondrially targeted antioxidants that extend life in mice I've discussed in the past:



It looks like the opportunists and less reputable traders have pretty much trampled "life extension" underfoot. As a term, it is coming to be associated only with those wretches clamoring to sell you potions, dreams, and nostrums:


"The term has solidly come to mean Revlon, skin cream, potions and the art of patching over the cracks so as to look younger, while doing absolutely nothing about the damage of aging. The forgery of the mirror and makeup, the magic show in which we expect to be entertained while understanding that none of it is real. ... This is the natural state of the world, in which the noble human aspects of profit motive and the burning desire for silver bullets and rapid answers to questions somehow combine to form twisted and generally worthless progeny. We humans excel at making a mess of noble beginnings, just as we excel in somehow pulling golden progress out of the dross that we forge.

"I don't believe that advocacy or research and development efforts for longevity science are in any way different from other human endeavors. Every new form of venture is fated to be beset by short-termists and gleeful miseducators as soon as it generates any niche that can be used to produce profit. You rise above them and achieve goals by demonstrating their labors to be pointless scratchings in the mud in the grand scheme of things - who should care an iota about antioxidant pills when we are within striking distance of completely replacing or repairing age-damaged mitochondria?"


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!




More Than You Ever Wanted to Know About DAF Gene Pathways (May 01 2009)
Daf-2 was one of the original longevity genes uncovered in nematode worms. Here, Ouroboros looks at the knowledge spiraling out from that discovery: "The insulin-like growth factor (IGF) pathway is one of the longest-known and well-studied regulators of longevity. Extracellular signals (insulin-like peptides) activate insulin-receptor homologs (in worm, DAF-2) which in turn recruit and activate phosphoinositol 3-kinases (AGE-1). PI3Ks convert PIP2 into PIP3, which tethers and recruits other kinases such as AKT-1. Eventually, activation of these upstream kinases results in phosphorylation and inactivation of the longevity assurance gene DAF-16, which encodes a transcription factor that activates (among many other things) stress resistance genes. ... And what does DAF-16 do? It heads to the nucleus and transcriptionally silences the genes encoding the upstream kinases DAF-2, AGE-1 and others - in other words, DAF-16 turns off the genes that could turn off DAF-16. It's a feedback loop! ... The authors argue that this arrangement represents a biological switch between a short-lived 'reproductive state' and a non-reproducing 'longevity state', characterized by DAF-16 activation of stress-resistance and other types of longevity assurance genes."

Working to Build Replacement Tissue (May 01 2009)
A look at what's going on the tissue engineering labs these days from ScienceDaily: "Cartilage, bones and the internal walls of blood vessels can be created by using common connective tissue cells from human skin. Researchers [have] successfully manipulated these tissue cells to take on different shapes depending on the medium they have been cultivated in. ... This means that it will be much easier to produce autologous tissue, which is tissue created from the patient's own body ... Different strategies have been attempted to instead grow autologous tissue from stem cells, for example those present in bone marrow. These cells, however, can be difficult to harvest, cultivate and store. Compared to these cells connective tissue cells from human skin has great advantages. A small biopsy is often enough to collect a sufficient amount of cells. ... They are the 'weed' cells of the body, very easy to collect and cultivate into the cell type required. They are also very suitable to use to create a personal cell bank. ... The dream is to be able to manipulate connective tissue cells in the human body to develop into specific cell types, for example to create bone cells for broken bones."

Revisiting Wine Consumption (April 30 2009)
A research group believes they have teased out the effects of wine consumption on life expectancy from all the confounding and related effects of diet and lifestyle. It'll take a few more such studies to convince me that this isn't just another artifact relating to inadvertent low-level calorie restriction, however. "Drinking up to half a glass of wine a day may boost life expectancy by five years ... The Dutch authors base their findings on a total of 1,373 randomly selected men whose cardiovascular health and life expectancy at age 50 were repeatedly monitored between 1960 and 2000. ... The researchers found that light long term alcohol consumption of all types - up to 20g a day - extended life by around two extra years compared with no alcohol at all. Extended life expectancy was slightly less for those who drank more than 20g. And men who drank only wine, and less than half a glass of it a day, lived around 2.5 years longer than those who drank beer and spirits, and almost five years longer than those who drank no alcohol at all. Drinking wine was strongly associated with a lower risk of dying from coronary heart disease, cerebrovascular disease, and death from all causes. These results held true, irrespective of socioeconomic status, dietary and other lifestyle habits, factors long thought to influence the association between wine drinking and better health."

Direct Cellular Reprogramming (April 30 2009)
Via EurekAlert!: "researchers describe how they are able to reprogram human adult skin cells into other cell types in order to decipher the elusive mechanisms underlying reprogramming. To demonstrate their point, they transformed human skin cells into mouse muscle cells and vice versa. This research shows that by understanding the regulation of cell specialization it may be possible to convert one cell type into another, eventually bypassing stem cells. ... Regenerative medicine provides hope of novel and powerful treatments for many diseases, but depends on the availability of cells with specific characteristics to replace those that are lost or dysfunctional. We show here that mature cells can be directly reprogrammed to generate those necessary cells, providing another way besides embryonic stem cells or induced pluripotent stem cells of overcoming this important bottleneck to restoring tissue function. ... Reprogramming mature cells will likely complement the use of embryonic stem cells in regenerating tissues. By elucidating the regulators of reprogramming [it] may be possible to generate replacement cells in cases where stem cells are not present or not appropriate."

A Better View of Parkinson's Disease (April 29 2009)
EurekAlert! notes a synthesis of previous Parkinson's disease research into a complete understanding of what is taking place: "In a study that reveals the clearest picture to date of neuron death in Parkinson's disease, researchers [have] found that a trio of culprits acting in concert is responsible for killing the brain cells ... symptoms of Parkinson's - including uncontrollable tremors and difficulty in moving arms and legs - are blamed on the loss of neurons from the substantia nigra region of the brain. Researchers had previously suspected dopamine, alpha-synuclein and calcium channels were involved in killing the neurons, but could not pin the deaths on any single molecule. The new paper, along with previous studies, [shows] that it is the combination of all three factors that kills the neurons. The studies found that neurons die because calcium channels lead to an increase of dopamine inside the cell; excess dopamine then reacts with alpha-synuclein to form inactive complexes; and then the complexes gum up the cell's ability to dispose of toxic waste that builds up in the cell over time. The waste eventually kills the cell. ... It may be possible to save neurons and stop Parkinson's disease by interfering with just one of the three factors."

Reverse Engineering the Brain (PDF) (April 29 2009)
From the latest issue of Biomedical Computation Review, a very readable article on the state of research into how our brains work. From the longer term perspective of longevity, this is important: we'd like to be able to replace our neurons with something more durable further down the line. "For a century, neuroscientists have dissected, traced, eavesdropped on, and are now compiling a seemingly endless cast of players in the nervous system. As we keep gathering more and more molecular details, how do we know when we know enough? ... Some have decided it's time to just go ahead and create a brain in silico. And to a surprising extent, they've done it: Labs around the world are populated with autonomously functioning [so far non-human, proof of concept] brains based on what we know so far. These simulations match what happens at the cellular level in the brain when the nerve cells, or neurons, that make up the brain pump ions and produce electrochemical activity that propagates across the synapse from one neuron to another. ... We can simulate the neuronal dynamics beautifully so that you can't tell the difference between the model and real neurons."

A Snapshot of Cell Reprogramming Research (April 28 2009)
From the Technology Review: "Treating embryonic cells from mice with a cocktail of proteins triggers production of new heart-muscle cells ... Working with mouse embryos about a week old, [researchers] discovered that a trio of proteins - including a pair of transcription factors and a protein that helps loosen tightly wound DNA - could direct certain embryonic cells to form cardiac-muscle cells, called cardiomyocytes. These cells not only produced proteins characteristic of early heart cells, but they eventually started to beat. ... Human trials of cell therapies for heart disease, which have mostly used stem cells derived from a patient's own blood, have yielded mixed results. It may be that transplanting cardiac myocytes rather than undifferentiated cells will prove more effective. ... we'd like to be able to make cardiac myocytes from any cell type. That would be the ideal therapy - to be able to turn those scar-tissue cells into cardiac myocytes and restore the function that's been lost ... The dream is to be able to take a skin cell or a cardiac fibroblast, any kind of cell a person has a lot to spare, and turn those into myocytes."

A Growing Interest in Heat Shock Proteins (April 28 2009)
A review paper from the community interested in metabolic manipulation to slow aging: "Heat-shock proteins (Hsps) are increasingly being implicated in aging phenotypes and control of life span across species. They are targets of the conserved heat-shock factor and insulin/IGF1-like signaling pathways that affect life span and aging phenotypes. Hsps are expressed in tissue-specific and disease-specific patterns during aging, and their level of expression and induction by stress correlates with and, in some instances, predicts life span. In model organisms, Hsps have been shown to increase life span and ameliorate aging-associated proteotoxicity. Finally, Hsps have emerged as key components in regulating aging-related cellular phenotypes, including cell senescence, apoptosis and cancer. The Hsps, therefore, provide a metric of individual stress and aging and are potential targets for interventions in aging and aging-related diseases." You might recall tha tthe cancer research community is also looking at how heat-shock proteins can be used to train the immune system to attack cancer cells.

A General Interest Calorie Restriction Article (April 27 2009)
From the Star-Telegram: "At 140 pounds and 6 feet tall, Fagg is bone thin. But his body mass index of 20 puts him within the optimal range for health. He might appear frail, but he is strong enough to do yoga and cardio workouts. If anyone doubts his fitness level, the 60-year-old Fagg is quick to challenge them to a hike from his home in Hurst to downtown Fort Worth. In 2007, he hiked down the north rim of the Grand Canyon and up the south rim, for a total of 65 miles, 13 of them straight up. 'My goal is to hike it again at 75,' Fagg said. He sees no reason why he won't be able to make it. Like many followers of the calorie restriction, or CR, lifestyle, Fagg hopes to live to be 100. But life extension is not the reason he eats so little. For Fagg and others, it's the health benefits that matter. ... Since the 1930s, researchers have documented the health benefits of calorie-restriction in animals, including a reduction in certain cancers. Although not a lot of research has been done on humans, two studies found that the probability of someone who practices CR coming down with diabetes was virtually nil."

More Reasons to Exercise (April 27 2009)
Via ScienceDaily: "moderate amounts of exercise alone can reduce the inflammation in visceral fat ... benefits of exercise were apparent, even without a change in diet. We saw improvements in insulin sensitivity, less fat in the liver, and less inflammation in belly fat ... Scientists now know that obesity is associated with a low-grade systemic inflammation. Obese people have higher levels of circulating inflammatory markers, such as C-reactive protein (CRP), which are produced and secreted by fat tissue. This inflammation then triggers the systemic diseases linked with metabolic syndrome, such as Type 2 diabetes and heart disease ... mice were assigned to either a sedentary group, an exercise group, a low-fat diet group, or a group that combined a low-fat diet with exercise ... The surprise was that the combination of diet and exercise didn't yield dramatically different and better results than diet or exercise alone." This suggests that the level of visceral fat is more important than other factors and whatever strategy you choose to get rid of it is going to provide some benefit. Which is not an excuse not to exercise or to overeat - a partial benefit is only a partial benefit.



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