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Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Valente, Joäo de Sousa 
Barrett, Brentton 
Smith, Matthew John 
Argunhan, Fulye 

Abstract

Ageing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α2c adrenoceptor expression in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.

Description

Keywords

TRPA1, TRPM8, ageing, biochemistry, chemical biology, cold response, mouse, thermoregulation, vascular response, Aging, Animals, Blood Circulation, Cold Temperature, Female, Mice, Nociception, Signal Transduction, Skin, TRPA1 Cation Channel, TRPM Cation Channels

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

10

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Versus Arthritis (ARUK21524)
British Heart Foundation (PG/12/34/29557, FS/19/42/34527)
Biotechnology and Biological Sciences Research Council (BB/P005616/1)