Format

Send to

Choose Destination
Cell. 2014 May 22;157(5):1023-36. doi: 10.1016/j.cell.2014.03.051.

TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling.

Author information

1
Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Glenn Center for Aging Research, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
2
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
3
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Glenn Center for Aging Research, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
4
The Glenn Center for Aging Research, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
5
Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
6
Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Glenn Center for Aging Research, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: dillin@berkeley.edu.

Abstract

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.

Comment in

PMID:
24855942
DOI:
10.1016/j.cell.2014.03.051
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center