TY - JOUR
T1 - TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling
AU - Riera, Céline E.
AU - Huising, Mark O.
AU - Follett, Patricia
AU - Leblanc, Mathias
AU - Halloran, Jonathan
AU - Van Andel, Roger
AU - De Magalhaes Filho, Carlos Daniel
AU - Merkwirth, Carsten
AU - Dillin, Andrew
PY - 2014/5/22
Y1 - 2014/5/22
N2 - The sensation of pain is associated with increased mortality, but it is unknown whether pain perception can directly affect aging. We find that mice lacking TRPV1 pain receptors are long-lived, displaying a youthful metabolic profile at old age. Loss of TRPV1 inactivates a calcium-signaling cascade that ends in the nuclear exclusion of the CREB-regulated transcriptional coactivator CRTC1 within pain sensory neurons originating from the spinal cord. In long-lived TRPV1 knockout mice, CRTC1 nuclear exclusion decreases production of the neuropeptide CGRP from sensory endings innervating the pancreatic islets, subsequently promoting insulin secretion and metabolic health. In contrast, CGRP homeostasis is disrupted with age in wild-type mice, resulting in metabolic decline. We show that pharmacologic inactivation of CGRP receptors in old wild-type animals can restore metabolic health. These data suggest that ablation of select pain sensory receptors or the inhibition of CGRP are associated with increased metabolic health and control longevity.
AB - The sensation of pain is associated with increased mortality, but it is unknown whether pain perception can directly affect aging. We find that mice lacking TRPV1 pain receptors are long-lived, displaying a youthful metabolic profile at old age. Loss of TRPV1 inactivates a calcium-signaling cascade that ends in the nuclear exclusion of the CREB-regulated transcriptional coactivator CRTC1 within pain sensory neurons originating from the spinal cord. In long-lived TRPV1 knockout mice, CRTC1 nuclear exclusion decreases production of the neuropeptide CGRP from sensory endings innervating the pancreatic islets, subsequently promoting insulin secretion and metabolic health. In contrast, CGRP homeostasis is disrupted with age in wild-type mice, resulting in metabolic decline. We show that pharmacologic inactivation of CGRP receptors in old wild-type animals can restore metabolic health. These data suggest that ablation of select pain sensory receptors or the inhibition of CGRP are associated with increased metabolic health and control longevity.
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U2 - 10.1016/j.cell.2014.03.051
DO - 10.1016/j.cell.2014.03.051
M3 - Article
C2 - 24855942
AN - SCOPUS:84901291766
VL - 157
SP - 1023
EP - 1036
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -