Endo-siRNA Induced Inactivation of a Neddylation Suppressor Promotes Longevity and Proteostasis in Germline-Less Animals

One way to slow aging in C. elegans is removing its germline. However, it is not clear how local changes in the reproductive system translate into physiological changes throughout the organism that increase lifespan. Small RNA molecules are putative signaling molecules that can spread and affect gene expression throughout the animal. In this study, we demonstrate for the first time the contribution of endogenous siRNA to longevity determination. Specifically, we find that mutations that disrupt the processing of endogenous siRNA molecules abrogate the lifespan extension and heat shock resistance of germlineless animals compared to animals with an intact reproductive system; implicating endogenous siRNA signaling in the reproductive longevity pathway. Insights into the underlying mechanism of this regulation will be discussed. Altogether, our data suggest that a novel siRNA signal can regulate proteostasis and aging throughout the animal; coupling them to the reproductive state of the animal.