Abstract: Excessive accumulation of reactive oxygen species (ROS) and Chronic activation of mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) result associated pathologies.Sestrin is a versatile anti-aging protein.Sestrin as a Prx Reductase or as a Peroxidase,which reduce ROS.Sestrin can upregulate autophagy and upregulate Nrf2 and its antioxidant targets,which inhibit ROS. Sestrin bind to GATOR2, On the one hand liberating GATOR1, and thereby promote the RagA/B-inhibiting activity.On the another hand activating AMPK which promote phosphorylation of TSC2,and thereby inhibit Rheb.Sestrin inhibit mTORC1 through its inhibition of RagA/B and Rheb.Concentration of leucine can change conformation of Sestrin,and thereby change its regulation of mTORC1.

Key words: Sestrin, ROS, mTORC1, leucine