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

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the post-transcriptional regulation of protein-coding genes. miRNAs modulate lifespan and the aging process in a variety of organisms. In this study, we identified a role of miR-83 in regulating lifespan of Caenorhabditis elegans. mir-83 mutants exhibited extended lifespan, and the overexpression of miR-83 was sufficient to decrease the prolonged lifespan of the mutants. We observed upregulation of the expression levels of a set of miR-83 target genes in young mir-83 mutant adults; while different sets of genes were upregulated in older mir-83 mutant adults. In vivo assays showed that miR-83 regulated expression of target genes including din-1, spp-9 and col-178, and we demonstrated that daf-16 and din-1 were required for the extension of lifespan in the mir-83 mutants. The regulation of din-1 by miR-83 during aging resulted in the differential expression of din-1 targets such as gst-4 and gst-10. In daf-2 mutants, the expression level of miR-83 was significantly reduced compared to wild-type animals. We identified a role for miR-83 in modulating lifespan in C. elegans and provided molecular insights into its functional mechanism. Copyright (C) 2018, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.