title: A steroid receptor-microRNA switch regulates life span in response to signals from the gonad.
abstract: Although the gonad primarily functions in procreation, it also affects animal life span. Here, we show that removal of the Caenorhabditis elegans germ line triggers a switch in the regulatory state of the organism to promote longevity, co-opting components involved in larval developmental timing circuits. These components include the DAF-12 steroid receptor, which is involved in the larval stage two-to-stage three (L2-L3) transition and up-regulates members of the let-7 microRNA (miRNA) family. The miRNAs target an early larval nuclear factor lin-14 and akt-1/kinase, thereby stimulating DAF-16/FOXO signaling to extend life. Our studies suggest that metazoan life span is coupled to the gonad through elements of a developmental timer.
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, D-50931 Cologne, Germany.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Shen
authors.forename: Joshua
authors.initials: J
authors.lastname: Wollam
authors.forename: Daniel
authors.initials: D
authors.lastname: Magner
authors.forename: Oezlem
authors.initials: O
authors.lastname: Karalay
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism; D006066:Gonads / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D051858:Forkhead Transcription Factors; C102669:LIN-14 protein, C elegans; D035683:MicroRNAs; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D051057:Proto-Oncogene Proteins c-akt; C494915:akt-1 protein, C elegans