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

• DOI: 10.7554/elife.50896
• Publication Date: 2020-03-26T13:00:16Z
• Authors: Moran Cohen-Berkman; Reut Dudkevich; Shani Ben-Hamo; Alla Fishman; Yehuda Salzberg; Hiba Waldman Ben-...; Ayelet T Lamm; Sivan Henis-Koren...
• Keywords: 0301 basic medicine; QH301-705.5; Science; endogenous siRNAs; Longevity; HSF1; germline; developmental biology; 03 medical and health sciences; longevity; cell biology; Animals; Biology (General); RNA, Small Interfering; Caenorhabditis elegans; Caenorhabditis elegans Proteins; proteostasis; Q; aging; R; Cell Biology; Germ Cells; C. elegans; Proteostasis; Medicine; Protein Tyrosine Phosphatases; Heat-Shock Response; Transcription Factors

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 Caenorhabditis 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.