Affiliation:
1. Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
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.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
398 articles.
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