Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans

We have identified a role of the C. elegans miR-83 in regulating lifespan. mir-83 mutants exhibit an extended lifespan, and its overexpression is sufficient to decrease the prolonged lifespan of the mutants. We observed an upregulation in the expression of sets of miR-83 targets in young mir-83 mutant adults. However, in older mir-83 mutant adults, a different set of genes are upregulated. In vivo assays show that miR-83 regulates expression of a number of targets, including din-1, spp-9 and col-178. We show that daf-16 and din-1 are required for the lifespan extension of mir-83 mutants. The regulation of din-1 by miR-83 during aging results in the differential expression of din-1 targets, such as gst-4 and gst-10. In daf-2 mutants, the expression levels of miR-83 are significantly reduced, as compared to wildtype animals. Our results identify a role of miR-83 in modulating lifespan in C. elegans, and provide molecular insights into its functional mechanism. Worms were cultured on FuDR-containing NGM plates until adult day 4 and day 12. Total RNA was extracted and then sequenced.