Journal Article Ppublish
PubMed: 40728520 DOI: 10.18632/aging.206290
Sesn-1 is required for lifespan extension during caloric deprivation in C. elegans through inhibition of mTORC1 and activation of autophagy.
Aging (Albany NY) 17(7):1834-1851
Authors: Andrei O Zheltukhin, Peter M Chumakov, Andrei V Budanov
Affiliations
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Abstract
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 sesn-1 gene on lifespan modulation during caloric deprivation (CD) in the model organism C. elegans. Our findings reveal that sesn-1 mediates lifespan extension under CD, primarily through the repression of mTORC1 kinase and activation of autophagy. Moreover, we identified an essential role for sesn-1 in enhancing stress resilience in nematodes, particularly in the context of nutrient sensing. Further investigations demonstrated sesn-1's interaction with the GATOR2 protein complex, its role in maintaining muscle integrity and a potential synergy between sesn-1 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.
MeSH
Autophagy, Aging, Stress, Physiological, Therapeutics, Mechanistic Target Of Rapamycin Complex 1