is required for lifespan extension during caloric deprivation in through inhibition of mTORC1 and activation of autophagy.

Sestrins, evolutionarily conserved stress-responsive proteins, are increasingly recognized for their potential role in lifespan regulation. This study aimed to elucidate the influence of the gene on lifespan modulation during caloric deprivation (CD) in the model organism . Our findings reveal that mediates lifespan extension under CD, primarily through the repression of mTORC1 kinase and activation of autophagy. Moreover, we identified an essential role for in enhancing stress resilience in nematodes, particularly in the context of nutrient sensing. Further investigations demonstrated 's interaction with the GATOR2 protein complex, its role in maintaining muscle integrity and a potential synergy between and the FOXO pathway. Overall, our research underscores the profound implications of Sestrins in aging and stress resistance, shedding light on possible therapeutic avenues for prevention and treatment of age-associated disorders.