Authors: Boehm, Michelle; Slack, Frank
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.
Keywords: Aging/genetics/physiology; Amino Acid Sequence; Animals; Caenorhabditis elegans/genetics/*physiology; Caenorhabditis elegans Proteins/genetics/metabolism/*physiology; Gene Expression Regulation, Developmental; Genes, Developmental; Heat-Shock Response; Insulin/metabolism; Insulin-Like Growth Factor I/metabolism; Lipofuscin/metabolism; Longevity/genetics/*physiology; MicroRNAs/*physiology; Molecular Sequence Data; Mutation; Nuclear Proteins/genetics/*physiology; RNA, Helminth/*physiology; Receptor, Insulin/metabolism; Repressor Proteins/*physiology; Signal Transduction; Transcription Factors/physiology|
Journal: Science Volume: 310 Issue: 5756 Pages: 1954-7 Date: Dec. 24, 2005 PMID: 16373574 |
Boehm, Michelle, Slack, Frank (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310: 1954-7.
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