Tubular lysosome induction couples animal starvation to healthy aging

Abstract Dietary restriction promotes longevity via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Using the nematode Caenorhabditis elegans , we show that induction of autophagic tubular lysosomes, which occurs upon dietary restriction or mTOR inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces tubular lysosomes not only in affected individuals but also in well-fed descendants, and the presence of gut tubular lysosomes in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila SVIP, a tubular-lysosome activator in flies, artificially induces tubular lysosomes in well-fed worms and improves C. elegans health in old age. These findings identify tubular lysosomes as a new class of lysosomes that couples starvation to healthy aging. One-Sentence Summary Tubular lysosome induction promotes healthy aging.