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
|
Resource |
C.elegans |
tm2869
tm1996
tm2001
tm2984
tm2001 |