TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Riera, CE; Huising, MO; Follett, P; Leblanc, M; Halloran, J; Van Andel, R; de Magalhaes Filho, CD; Merkwirth, C; Dillin, A

Published Date

  • May 2014

Published In

Volume / Issue

  • 157 / 5

Start / End Page

  • 1023 - 1036

PubMed ID

  • 24855942

Pubmed Central ID

  • 24855942

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.03.051

Language

  • eng