Fig. 2.

Rapamycin regulates lifespan primarily through the mTOR signaling pathway. mTOR exists mainly in two functionally distinct complexes termed mTORC1 and mTORC2. Rapamycin inhibits mTORC1 on an intermittent basis, while long-term administration also inhibits mTORC2 in most tissues. Inhibition of mTORC1 promotes protein and nucleotide synthesis as well as autophagy responses, while also reducing cellular stress responses. These effects of rapamycin may promote longevity. In contrast, inhibition of mTORC2 leads to metabolic dysfunction and reduced lifespan, but the exact mechanism is unclear