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Science 310 (5756): 1954-1957

Copyright © 2005 by the American Association for the Advancement of Science

A Developmental Timing MicroRNA and Its Target Regulate Life Span in C. elegans

Michelle Boehm, and Frank Slack*

Abstract: The microRNA lin-4 and its target, the putative transcription factor lin-14, control the timing of larval development in Caenorhabditis elegans. Here, we report that lin-4 and lin-14 also regulate life span in the adult. Reducing the activity of lin-4 shortened life span and accelerated tissue aging, whereas overexpressing lin-4 or reducing the activity of lin-14 extended life span. Lifespan extension conferred by a reduction in lin-14 was dependent on the DAF-16 and HSF-1 transcription factors, suggesting that the lin-4–lin-14 pair affects life span through the insulin/insulin-like growth factor–1 pathway. This work reveals a role for microRNAs and developmental timing genes in life-span regulation.

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.

* To whom correspondence should be addressed. E-mail: frank.slack{at}yale.edu

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