Endogenous siRNAs promote proteostasis and longevity in germline-less Caenorhabditis elegans

How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in C.CaenorhabditisC. elegans elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity. glp-1(e2144) and dcr-1(mg375) glp-1(e2144) C. elegans were raised at 25 degrees until day 1 of adulthood. Low molecular RNA fraction was extracted using miRVana miRNA isolation kit (Ambion). Library preparation was done using QsRNA-seq protocol that mainly captures secondary siRNAs.