mTORC2

Here's TOR.

It's actually in two complexes, TORC1, TORC2.

They do slightly different things.

OK, it's complicated.

So mTOR1 is like the brain of our cells.

mTOR2 controls our cell survival.

When mTOR gets overactive, we lose muscle and it accelerates our aging.

Too much mTOR can also fuel proliferation of cancer cells.

Rapamycin hits mTOR1, which is the arm tied to growth and cell repair, which is where the longevity benefits seem to come from.

But at higher doses or long-term lower doses, it splits over into mTORC2, which handles insulin signaling and other metabolic housekeeping, and you don't want to mess with those.

So even at transplant-level doses, the side effects of rapamycin are a problem.

Oh, mouth ulcers, impaired wound healing, elevated lipids in your blood, insulin resistance, changes in your immune system.

Yeah.

So the reason it works is because it's also an mTOR inhibitor, mTORC1 and mTORC2.

So that's why you're seeing the benefit in mutant and wild types as well.

And whether to use CAPI versus using get a tolicib, I think, again, you're having an oral drug versus an IV agent.