Thursday, January 5, 2012

AGEING. mTOR, rapamycine and calorie restriction.

i just read an article in Scientific American on ageing and developments in creating an antiageing drug and thought id share my thoughts on it. i have an aversion and a great suspicion about concentrating scientific exploration around "curing" everything with drugs plus i have been interested in antiageing info for a while and have been following up on it as often as newer info pops up. i think its already common knowledge, at least in circles imbued in nutrition sciences, that calorie restriction is sofar the only and best way to extend human life. why it is so has been clearing up during the past ten years. the most interesting research has been concentrating on evolutionary theories (my favourite) about the so-called "two-faced" genes that express for cell proliferation and growth and are useful in childhood through to reproduction but after that their purpose kinda swiches - and they age you instead. the thing is, evolutionarily speaking, nature doesnt care how long we live, or what the "quality" of those later years are (our healthspan). evolution just needs us to reproduce. some years ago, due to a cancer in the family, i started to read up on cancer genetics (causes of cell proliferation) and stumbled upon Mikhail Blagosklonny`s research. strangely his article also popped up in the Scientific American article i just read. he talks about a protein mTOR and its effects on the growth of human cells and ageing. mTOR is a protein that is a product of a "two-faced" gene. its production increases when there's plenty of food around in the human system and through pathways that also trigger insulin and IGF (insulin like growth-factor), it prompts cell-proliferation and inhibits autophagy (recycling of dead and damaged cell-components and proteins). that is positive when you are still a growing organism. not so for an adult. too much mTOR can induce insulin resistance, cause unwanted cell growth and promote cellsenesence (a cell grows to abnormal proportions and becomes toxic to its neighbours). when food is scarce the scenario is reversed - mTOR is inhibited, cell growth slows, autophagy is vamped up - ageing slows as a result.

the article i read dismissed calorie restriction for humans as something that is hard to achieve for most mortals and concentrated on rapamycin - a promising new antiaging drug (a fungal inhibitor that has been used in cancer treatments due to its function in inhibiting growth of tumor cells) that works by inhibiting mTOR. the drug added a phenomenal 38 5 to female labmice life-expectancy (and 28% to the males`). the problem is its side effects - it is an immunosuppressant and therefore its longtime use could lead to toxicity. towards the end of the article the author suggests metformin ( a widely used diabetes drug) as a possible candidate for a miricle antiageing agent - as it also inhibits the mTOR pathway in humans.

it is all fine and dandy and definitely intriguing as hell. and just as annoying for me as a hard-boiled IF proponent. to just discard the one and proven way to slow the ageing process as unattainable for us mortals because of what.... we dont have enough willpower to stop gorging ourselves so we need a pill to fix everything. its the same with diabetes treatment - eat anything you want, just inject enough insulin. anybody thats suggests otherwise (as in dich the carbs) and dares to write about it might just get sued in this country (Finland). ofcourse the possibility of intermittent fasting to achieve the necessary 30% cut in calories to achieve the desired mTOR inhibiting effect has never been discussed. i doubt it has ever passed a scientists mind - or atleast the publication-bravery threshold. and different  macronutrients effect on mTOR wasn't even mentioned in the article. for example, we know that a high protein diet has its activating effects on mTOR because the aminoacid leucine promotes the activation mTOR and therefore allows for increased protein synthesis in skeletal muscle (greatly desired by bodibuilders). leucine also promotes gluconeogenesis and aids in the retention of lean mass in a fasted state  (is that such a bad thing)?

what would happen to mTOR regulation and human ageing if a lowcarb diet (i advocate moderate protein) and IF would be combined? on one hand promoting mTOR to keep lean muscle mass and on the other ramping up autophagy during the fasting periods and adding to healthy longevity?? anybody here got funds to study that id greatly appreciate it.

1 comment:

  1. Ketogenic diets inhibit mTOR. We don't have to starve, just cut the carbs. :)


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