Nothing is More Interesting than Rapamycin

March 14, 2016

Nothing is More Interesting than Rapamycin 

 Reference: AntiOxid and Redox Signal 2015, Chris Kresser Podcast, Nature 

 Published:  March 14, 2016 

 Rapamycin? Sounds like an antibiotic. It is! And it might be the most interesting antibiotic ever.   What makes it interesting is that it impacts the mTOR pathway, which is the most primitive pathway of metabolism of all, applying to virtually every living creature. (mTOR means “mechanistic target of rapamycin”)   

Rapamycin is the only known chemical that modulates aging in all four model species: yeast, worm, flies and mammals. Rapamycin is so named because it was found on the island Rapa Nui, which is what natives call Easter Island. The strain of Streptomyces (an actinomycetes) in which it was found was unique to Easter Island. A research group from McGill University went there looking for new strains of actinos from which to extract antibiotics.   Suren Sehgal was the researcher working for Ayerst Labs who isolated it and found it to be an amazing cure for athlete’s foot. But Ayerst Lab went belly up so Sehgal saved the rapamycin and hid it in his freezer until Wyeth Labs bought out the rights of the company. 

 But it was not until the early 90s that a PhD student named David Sabitini doing research on stroke reperfusion used rapamycin as a control drug. He refused to do the easy study that his supervisor wanted him to work on, and instead went off on a tangent. Sabitini wanted to figure out just how rapamycin worked, and ended up discovering the mTOR protein complex.   

MTOR turns out to be a master regulator of protein translation, cell growth, and proliferation.   And for a whole host of reasons, these actions end up being smack dab in the middle of understanding how cancer gets out of sync, and how aging wears us down. So, just how does rapamycin work?   

How does mTOR work? Rapamycin works by flipping a switch in cells that sense nutrients in the environment. The cells think they are starving. Crisis! Hunker down and go into slow mode. Sabatini also found RAPTOR, (rapamycin associated protein) that regulates cell size in response to the level of environmental food supply. And then there is GβL that regulates how Raptor and mTOR interact. There is mTORC1 and mTORC2 which are in different tissues in different concentrations, but all on the same theme.   We now have a chemical that induces resistance to aging through the same pathway as calorie restriction. Calorie restriction only works well if started at birth. 

Rapamycin adds its benefit when ever it’s started. Just what could Rapamycin do for us? Right now, we aren’t really sure except that it is an amazing research tool that is helping unpack the complexities of human biology. In mice we know that intermittent dosing of rapamycin prolongs life substantially, mimicking calorie restriction. We do know that nutrient manipulation in cancer is incredibly powerful, and this approach may lead us to a path that confirms exactly how that works. 

 WWW. What will work for me? The clear message is that calorie restriction slows down aging. We know that autophagy (cleaning out old, used up cells) is enhanced by calorie restriction, and it’s effect is accelerated by rapamycin. That is something everyone should be interested in because lousy autophagy is central to Alzheimer’s. And green tea (EGCG) inhibits mTOR. That’s part of its effect on cancer. So, I’m paying attention to mTOR. I’ve almost switched all my tea to green. Thought you should too. Eventually, we may all be taking it as our morning mTOR stimulation.   

 Pop Quiz

  1. Rapamycin was named after a fungus found on Easter Island? T or F              Answer: That’s it, Rapa Nui
  1. Rapamycin is a powerful anti-fungal antibiotic that appears to block your body’s sensor of calories? T or F                  Answer: Perfect.                                                                                                                   
  1. MTOR is the protein complex that inhibits rapamycin. T or F                  Answer:  False. mTor is one of several proteins that rapamycin inhibits. That’s vice versa.
  1. Rapamycin induces longer life in every model of animal it’s been studied, from yeast to mammals. T or F                  Answer:  True
  1. Calorie restriction can prolong life? T or F                  Asnwer:  True, but probably more effectively starting earlier than later.
  1. Rapamycin may have beneficial effects on aging, cancer, Alzheimer’s, diabetes? T or F             Answer:  True.