Overexpression Extends Lifespan and Healthspan in .

Autophagy plays important but complex roles in aging, affecting health and longevity. We found that, in the general population, the levels of and decreased during aging, yet they are upregulated in centenarians, suggesting that overexpression of ATG4 members could be positive for healthspan and lifespan. We therefore analyzed the effect of overexpressing (a homolog of human ) in , and found that, indeed, overexpression increased resistance to oxidative stress, desiccation stress and fitness as measured by climbing ability. The overexpression induced since mid-life increased lifespan. Transcriptome analysis of subjected to desiccation stress revealed that overexpression increased stress response pathways. In addition, overexpression of delayed cellular senescence, and improved cell proliferation. These results suggest that have contributed to a slowdown in cellular senescence, and in , overexpression may have led to improved healthspan and lifespan by promoting a stronger stress response. Overall, our study suggests that and have the potential to become targets for health and lifespan interventions.