RRC ID 53512
Author Chen YC, Chen HJ, Tseng WC, Hsu JM, Huang TT, Chen CH, Pan CL.
Title A C. elegans Thermosensory Circuit Regulates Longevity through crh-1/CREB-Dependent flp-6 Neuropeptide Signaling.
Journal Dev Cell
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.
Volume 39(2)
Pages 209-223
Published 2016-10-24
DOI 10.1016/j.devcel.2016.08.021
PII S1534-5807(16)30596-2
PMID 27720609
MeSH Animals Body Temperature / physiology* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Genes, Helminth Heat-Shock Response / genetics Hot Temperature Interneurons / metabolism Intestinal Mucosa / metabolism Longevity / physiology* Models, Biological Mutation / genetics Neuropeptides / genetics Neuropeptides / metabolism* Peptide Hormones / metabolism Sensory Receptor Cells / metabolism Signal Transduction* / genetics Transcription Factors / metabolism* Transcription, Genetic
IF 10.092
Times Cited 19
C.elegans tm2869 tm1996 tm2001 tm2984 tm2001