# Sesn-1 is required for lifespan extension during caloric deprivation in C. elegans through inhibition of mTORC1 and activation of autophagy

## TL;DR

The study shows that the sesn-1 gene helps extend lifespan in C. elegans during caloric restriction by controlling mTORC1 and boosting autophagy.

## Contribution

The novel contribution is identifying sesn-1's role in lifespan extension through mTORC1 inhibition and autophagy activation during caloric deprivation.

## Key findings

- Sesn-1 mediates lifespan extension under caloric deprivation via repression of mTORC1 and activation of autophagy.
- Sesn-1 enhances stress resilience in C. elegans, particularly in nutrient sensing contexts.
- Sesn-1 interacts with GATOR2, maintains muscle integrity, and synergizes with the FOXO pathway.

## 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.