Sestrins as modulators of aging processes and diseases related to age

Abstract

Sestrins are highly conserved proteins that regulate cell growth, metabolism, survival and proliferation under oxidative stress, genotoxic stress, hypoxia or endoplasmic reticulum stress. Sestrins affect cell signaling by inhibiting the production of reactive oxygen species, activating the AMP-activated protein kinase (AMPK), inhibiting the mTOR pathway and acting as a positive regulator of autophagy. Therefore, their protective role against cancer, metabolic disorders, cardiovascular diseases and neurodegeneration is increasingly being postulated. The article describes the mechanisms of action of sestrins and their meaning in aging and age-related diseases. The latest studies indicating their physiological significance and role in key signaling pathways controlling the cell metabolism and survival under stress conditions were also discussed.