title: A C. elegans Thermosensory Circuit Regulates Longevity through crh-1/CREB-Dependent flp-6 Neuropeptide Signaling.
abstract: Sensory perception, including thermosensation, shapes longevity in diverse organisms, but longevity-modulating signals from the sensory neurons are largely obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD thermosensory neuron is a key mechanism that maintains lifespan at warm temperatures in C. elegans. In response to temperature rise and crh-1 activation, the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1 and FLP-6 are necessary and sufficient for longevity at warm temperatures. Our data suggest that FLP-6 targets the AIY interneurons and engages DAF-9 sterol hormone signaling. Moreover, we show that FLP-6 signaling downregulates ins-7/insulin-like peptide and several insulin pathway genes, whose activity compromises lifespan. Our work illustrates how temperature experience is integrated by the thermosensory circuit to generate neuropeptide signals that remodel insulin and sterol hormone signaling and reveals a neuronal-endocrine circuit driven by thermosensation to promote temperature-specific longevity.
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
authors.forename: Yen-Chih
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
authors.forename: Hung-Jhen
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
authors.forename: Wei-Chin
authors.initials: WC
authors.lastname: Tseng
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
authors.forename: Jiun-Min
authors.initials: JM
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
authors.forename: Tzu-Ting
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan. Electronic address: chunliangpan@gmail.com.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Pan
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D017238:Genes, Helminth; D018869:Heat-Shock Response / Q000235:genetics; D006358:Hot Temperature; D007395:Interneurons / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D036361:Peptide Hormones / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C556191:CRH-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C525653:Ins-7 protein, C elegans; D009479:Neuropeptides; D036361:Peptide Hormones; D014157:Transcription Factors