Evidence that mTORC2 inhibition is detrimental, by Dudley Lamming

Rapamycin, when taking at high doses on a continual basis, is known to eventually start to inhibit mTORC2. One of the results of ongoing mTORC2 inhibition is immune system suppression (while this is considered a feature, not a bug, in organ transplant patients, in anti-aging its definitely a “bug” (negative). Research also suggests that mTORC2 inhibition shortens healthspan and lifespan in animals.

These are the reasons why, for rapamycin in anti-aging, we typically take rapamycin on a pulsed dosing schedule (e.g. once per week or once every two weeks).

Here is a twitter thread where one of the leading researchers on rapamycin and mTOR outlines the evidence on mTORC2 inhibition:

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He also seems to say the jury is still out on whether all mTORC2 inhibition is detrimental, and there is plenty more to learn about the many downsides.

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And today:

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Lamming has developed new rapalogs that ONLY target mTORC1.

“DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced or no side effects on lipid metabolism and the immune system”

But they are a long way from FDA approval…