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

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Science  23 Dec 2005:
Vol. 310, Issue 5756, pp. 1954-1957
DOI: 10.1126/science.1115596

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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-4lin-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.

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