Tissue-specific requirement of the autophagy gene atg-18 in controlling C. elegans dauer morphogenesis, fat metabolism and adult longevity

The conserved insulin growth factor IGF signaling pathway is one of the major regulators of lifespan in many species including C. elegans. In C. elegans the insulin/IGF-like receptor is encoded by the daf-2 gene, mutations in which result in lifespan extension, fat accumulation and dauer formation. The daf-2 activity in the nervous system controls these phenotypes cell non-autonomously. Interestingly, the longevity phenotype of daf-2 mutant worms is dependent on macroautophagy hereafter autophagy. Autophagy is a highly conserved lysosomal degradation pathway involved in the removal of long-lived proteins and cytoplasmic organelles. During autophagy, cellular components are sequestered into the double-membrane autophagosomes and delivered to lysosomes for degradation. Increasing evidence has emerged that the autophagy process is a central regulator of lifespan that is required for the effects of DAF-2 signaling, dietary restriction and some mitochondrial mutations on C. elegans longevity. It is unknown however whether autophagy activity in every tissue or in a single tissue mediates the influence of these longevity signals. To address this question, we examined the tissue requirement of autophagy gene atg-18 for the lifespan of wild type animals and the daf-2 mutant. We discovered that neurons and intestinal cells are two key tissues where atg-18 mediates the effect of DAF-2 insulin-like signaling on lifespan, fat accumulation and dauer morphogenesis, suggesting autophagy acts cell non-autonomously in controlling C. elegans dauer formation, fat metabolism and adult longevity.