Quercetin inhibits PI3K/AKT/mTOR signaling and activates AMPK — the two master regulators of autophagy. In aging cells, mTOR activity is elevated and AMPK activity is reduced, suppressing autophagy and allowing damaged protein and organelle accumulation. Quercetin partially reverses this age-related shift in autophagic activity.

Is quercetin better or worse than rapamycin for autophagy?

Rapamycin is a far more potent and specific mTOR inhibitor than quercetin (100–1,000x lower concentration required). Quercetin's modest mTOR inhibition is supplemented by AMPK activation and Beclin-1 upregulation, which rapamycin does not provide. They have complementary (not interchangeable) profiles.

Should I take quercetin while fasting for maximum autophagy?

Taking quercetin in a fasted state (or at least carbohydrate-restricted) maximizes the mTOR inhibitory effect. Food and particularly insulin signaling (from carbohydrates) activates mTOR, partially opposing quercetin's mTOR inhibition.