A Few Interesting Recent Research Publications

Via the science watchers who post to sci.life-extension, I noticed a couple of interesting recent papers.

An anti-aging drug today: from senescence-promoting genes to anti-aging pill

Numerous mutations increase lifespan in diverse organisms from worms to mammals. Most genes that affect longevity encode components of the target of rapamycin (TOR) pathway, thus revealing potential targets for pharmacological intervention. I propose that one target, TOR itself, stands out, simply because its inhibitor (rapamycin) is a non-toxic, well-tolerated drug that is suitable for everyday oral administration. Preclinical and clinical data indicate that rapamycin is a promising drug for age-related diseases and seems to have anti-tumor, bone-sparing and calorie-restriction-mimicking 'side-effects'. I also discuss other potential anti-aging agents (calorie restriction, metformin, resveratrol and sirtuins) and their targets, interference with the TOR pathway and combination with antioxidants.

Calorie restriction mimetics are attracting a great deal of funding these days, which of course means that researchers are picking back through the existing drug library in search of items that might be useful (or, cynically, made fundable) in this context. Chris Patil of Ouroboros is skeptical in this case:

I’m a little surprised that the author is proposing that rapamycin itself be used as an anti-aging drug: it’s an immune suppressant used to prevent transplant rejection, after all, and long-term immune suppression is usually considered one of the downsides of receiving a transplant. Furthermore, there are concerns that rapamycin can impair wound healing - another trait I wouldn’t look for in a chronically administered pharmaceutical.

He suggests that the paper is much more interesting for its discussion of the TOR pathway; how researchers presently think it fits in with the beneficial effects of calorie restriction on healthy longevity. It's a good reminder that sirtuins are not the end of the path insofar as the biochemistry of calorie restriction goes. There is much more yet to come.

Epigenetic control of hematopoietic stem cell aging, the case of Ezh2

During aging the integrity and functioning of a wide variety of tissues is gradually deteriorating, ultimately resulting in a spectrum of diseases, including cancer. We propose that somatic stem cells, which can be found in most adult tissues, play a crucial role in the aging process. We recently described that enforced overexpression of the chromatin modifying Polycomb group gene Ezh2 results in prevention of stem cell exhaustion. This provides a novel insight into the molecular pathways regulating this process, and we hypothesize that chromatin modifications play a key role in maintaining a stem cell-specific transcriptome. It is likely that the identification and functional characterization of genes that affect chromatin modifications in stem cells will provide important information on the molecular mechanisms that regulate cellular aging.

You might recall that recent study on Polycomb genes; I noted at the time that, if we're lucky, the root of all cancer may just look something like this - a matter of stem cell regulation at the epigenetic level, and cancers resulting from nothing more than aging stem cells run amok. But any insight into stem cell regulation across a lifetime also helps us to understand the mechanisms behind the decline in stem cell activity with age; it seems obvious that this decline is an anti-cancer adaptation, but how does it work? If we don't know how it works, it'll be hard to do something about the problem.

It seems too much to hope for that the understanding needed to maintain the regenerative capacity of stem cells with age will be the very same understanding needed to prevent most cancers - but you never know.

Let's finish up with more scientific support for common sense health practices:

Unhealthy lifestyles during the life course: association with physical decline in late life

These data suggest that overweight in old age, and chronic exposure to physical inactivity or overweight throughout life, increases the risk of physical decline in old age. Therefore, physical activity and prevention of excessive weight at all ages should be stimulated, to prevent physical decline in old age.

It's not rocket science; listening what your doctor tells you to do in terms of health basics will make a great deal of difference over a lifetime. Calorie restriction makes even more of a difference on top of that. A golden future of greatly extended longevity, cures for all disease and wonderous technology lies a bare handful of decades ahead. A revolution of accelerating growth in the enabling technologies of medicine is in full swing. Do you really want to throw away the very decades of your life that will enable you to live into the era to come? Take care of the health basics - care today will pay great rewards in the long run.

Technorati tags: aging, health, life extension, medical research

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