Autophagy gene atg-18 regulates C. elegans lifespan cell nonautonomously by neuropeptide signaling

In the round worm C. elegans, it has recently been shown that autophagy, a highly
conserved lysosomal degradation pathway that is present in all eukaryotic cells, is
required for maintaining healthspan and for increasing the adult lifespan of worms fed
under dietary restriction conditions or with reduced IGF signaling. It is currently
unknown how extracellular signals regulate autophagy activity within different tissues
during these processes and whether autophagy functions cell-autonomously or nonautonomously.
We have data that for the first time shows autophagy activity in the
neurons and intestinal cells plays a major role in regulating adult lifespan and the
longevity conferred by altered IGF signaling and dietary restriction, suggesting
autophagy can control these phenotypes cell non-autonomously. We hypothesize that
autophagy in the neurons and intestinal cells is an essential cellular process regulated by
different signaling pathways to control wild type adult lifespan, IGF mediated longevity and dietary restriction induced longevity. Excitingly we also have found that in animals
with reduced IGF signaling autophagy can control longevity in only a small subset of
neurons alone. Autophagy in either specific individual chemosensory neurons or a small
group of them is completely sufficient to control IGF mediated longevity. This work
provides novel insight to the function and regulation of autophagy which will help shed
light on understanding this essential process in higher organisms, including mammals.