mTOR Science- Muscle Growth vs. Longevity

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Mammalian target of rapamycin (mTOR) was named because a drug called rapamycin inhibited a protein that was then named, target of rapamycin (TOR). The “m” is because it’s in mammals (zebra fish TOR is, similarly, zTOR).

mTOR is central to the opposing biological processes of growth and longevity. mTOR is thought to promote growth and decrease longevity.

Basically, any process you can think of relating to muscular growth and longevity probably has some relationship to mTOR. Here are some examples:

Exercise activates mTOR signaling in skeletal muscles (growth)
mTOR inhibits autophagy (longevity)
Insulin activates mTOR (growth)
Sirtuin proteins inhibit mTOR (longevity)
BCAAs activate mTOR (growth)
Fasting inhibits mTOR (anti-growth and longevity)
And, as precited by its pathetic name, rapamycin increases (longevity), at least in mice

How exactly does mTOR impact all these processes? Well, it’s kind complicated [show image below] and there are actually two different mTOR complexes (mTOR1 and mTOR2) that have slightly different functions. So, for the sake of simplicity let’s just say this: mTOR is a kinase. This means that mTOR acts to regulate the activities of other proteins by adding a phosphate group from ATP to them. Depending on what protein it adds the phosphate to, and where on that protein it does so, is can either activate of inhibit its target and pathways downstream.

The message, in its simplest form, is that mTOR activity makes you live hot (and strong) but die young. But since when is science ever simple? What annoys me is that people tend to be scared of anything that activates mTOR because they are afraid it’s going to kill them. This is problematic thinking for two reasons:

(1) Biology is all about balanced cycles. You need periods of growth (anabolism) and breakdown (catabolism). If you’re all anabolism (like a body builder) you will die young. However, if you’re all catabolism, you’ll die even younger. In fact, one of the leading risk factors for death in the elderly is low muscle mass. You need a functional level of muscular power to live and thrive. No mTOR and you’d wither away. In short, you do want to activate mTOR on occasion. Just don’t overdo it. “Extremes are easy, the challenge is balance.” “

(2) The inside of your body is NOT a homogenous blob! Why do people always forget that fact? Just because you activate mTOR in once place doesn’t mean you activate it everywhere. For example, when you work out you activate mTOR in your skeletal muscle but might actually decrease mTOR activity in your brain. Thus, it’s possible, and I would argue probable (such studies can’t be done in humans without cutting into their brains), that exercise activates muscular mTOR but inhibits brain mTOR, giving you the exact organ-specific balance of activity that you want!

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Nicholas Norwitz - Oxford PhD Researcher and Harvard Med Student:
https://www.dpag.ox.ac.uk/team/nichol...