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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Aging / genetics
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Aging / physiology
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Caenorhabditis elegans Proteins / physiology*
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Forkhead Transcription Factors
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Gene Expression Regulation, Developmental
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Genes, Developmental
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Heat-Shock Response
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Insulin / metabolism
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Insulin-Like Growth Factor I / metabolism
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Lipofuscin / metabolism
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Longevity / genetics
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Longevity / physiology*
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MicroRNAs / physiology*
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Molecular Sequence Data
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Mutation
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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RNA, Helminth / physiology*
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Receptor, Insulin / metabolism
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Repressor Proteins / physiology*
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Signal Transduction
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Transcription Factors / physiology
Substances
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Caenorhabditis elegans Proteins
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Forkhead Transcription Factors
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Insulin
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LIN-14 protein, C elegans
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Lipofuscin
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MicroRNAs
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Nuclear Proteins
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RNA, Helminth
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Repressor Proteins
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Transcription Factors
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daf-16 protein, C elegans
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lin-4 microRNA, C elegans
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Insulin-Like Growth Factor I
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DAF-2 protein, C elegans
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Receptor, Insulin