Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila.

ABSTRACT: Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5. We next directly induced autophagy by over-expressing the major autophagy kinase Atg1 and found that a mild increase in autophagy extended lifespan. Interestingly, strong Atg1 up-regulation was detrimental to lifespan. Transcriptomic and metabolomic approaches identified specific signatures mediated by varyi

SUBMITTER: Bjedov I 

PROVIDER: S-EPMC7738165 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature