Bacterial RNA promotes proteostasis through inter-tissue communication in C. elegans

Life expectancy has been increasing over the last decades, which is not matched by an increase in healthspan. Besides genetic composition, environmental and nutritional factors influence both health- and lifespan. Diet is thought to be a major factor for healthy ageing. Here, we show that dietary RNA species extend healthspan inC. elegans. Inherent bacterial-derived double stranded RNA reduces protein aggregation in aC. elegansmuscle proteostasis model. This beneficial effect depends on low levels of systemic selective autophagy, the RNAi machinery in the germline, even when the RNA is delivered through ingestion in the intestine and the integrity of muscle cells. Our data suggest a requirement of inter-organ communication between the intestine, the germline and muscles. Our results demonstrate that bacterial-derived RNAs elicit a systemic response inC. elegans, which protects the animal from protein aggregation during ageing. We provide evidence that low stress levels are beneficial for healthspan. Overall design: To investigate whether any or a specific bacterial-derived RNA would protectC. elegansfrom protein aggregate accumulation and promote proteostasis, we performed total RNA seq and smRNA seq on the three bacterial strains (OP50, OP50(xu363) and HT115)using both total RNA and a library enriched for small RNA molecules.