MicroRNAs both promote and antagonize longevity in C. elegans

Alexandre De Lencastre, Zachary Pincus, Katherine Zhou, Masaomi Kato, Siu Sylvia Lee, Frank J. Slack

Research output: Contribution to journalArticlepeer-review

243 Scopus citations


Background: Aging is under genetic control in C. elegans, but the mechanisms of life-span regulation are not completely known. MicroRNAs (miRNAs) regulate various aspects of development and metabolism, and one miRNA has been previously implicated in life span. Results: Here we show that multiple miRNAs change expression in C. elegans aging, including novel miRNAs, and that mutations in several of the most upregulated miRNAs lead to life-span defects. Some act to promote normal life span and stress resistance, whereas others inhibit these phenomena. We find that these miRNAs genetically interact with genes in the DNA damage checkpoint response pathway and in the insulin signaling pathway. Conclusions: Our findings reveal that miRNAs both positively and negatively influence life span. Because several miRNAs upregulated during aging regulate genes in conserved pathways of aging and thereby influence life span in C. elegans, we propose that miRNAs may play important roles in stress response and aging of more complex organisms.

Original languageEnglish
Pages (from-to)2159-2168
Number of pages10
JournalCurrent Biology
Issue number24
StatePublished - Dec 21 2010


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