mTOR activation, ATG13 inactivation and suppression of autophagy

That diagram from the video shows the rationale for the use of the Sim501 compound, in their attempt to make a drug induced model of PEM, which is the thing I wasn't sure about from my first listen.

When mTOR is inactivated, ATG13 participates in processes leading to autophagy.
When mTOR is activated, ATG13 is phosphorylated and inactivated, leading to disturbances in autophagy.
SIM50 is reported to activate mTOR. So the mouse model involves activating mTOR via this drug.

With the effect of the drug wearing off in the mice after a month, the question then becomes 'what is activating mTOR, and why does it remain activated?'.

I agree @belbyr, I'm happy that these researchers are working on this.

I don't think it is said, but I think SIM501 might be simvastin, a statin.

[deleted a bit that is an unnecessary diversion]
Does anyone here know for sure what SIM501 is?

 

Ah yes, that makes sense, I got tangled up in finding a statin referred to as SIM10 and making leaps from there. There's this paper https://pubmed.ncbi.nlm.nih.gov/23817226/
where the statin inhibits mTOR and increases autophagy. As you say, the opposite result from what these researchers did in trying to create a mouse model of PEM.

Some of our members will be on statins, I wonder if they have noticed any benefits.

 

Yes, we have a few threads on rapamycin e.g.
Rapamune / Rapamycin/ mTOR
Results reported by members are variable but don't seem to be of the 'this cured me' type. And there's quite a lot of downside - an immune-suppressor in a pandemic...