A developmental timing microRNA and its target regulate life span in C. elegans.
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.
Boehm
Michelle
M
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Slack
Frank
F
D000375:Aging / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental; D018869:Heat-Shock Response; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008062:Lipofuscin / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D018510:RNA, Helminth / Q000502:physiology*; D011972:Receptor, Insulin / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; C102669:LIN-14 protein, C elegans; D008062:Lipofuscin; D035683:MicroRNAs; D009687:Nuclear Proteins; D018510:RNA, Helminth; D012097:Repressor Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C452194:lin-4 microRNA, C elegans; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin