Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.
Valente, Joäo de Sousa
Smith, Matthew John
Lee, Sheng Y
eLife Sciences Publications, Ltd
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Thapa, D., Valente, J. d. S., Barrett, B., Smith, M. J., Argunhan, F., Lee, S. Y., Nikitochkina, S., et al. (2021). Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.. Elife, 10 https://doi.org/10.7554/eLife.70153
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.
Research Article, Biochemistry and Chemical Biology, ageing, TRPM8, TRPA1, cold response, vascular response, thermoregulation, Mouse
Biotechnology and Biological Sciences Research Council (BB/P005616/1)
Versus Arthritis (ARUK21524)
British Heart Foundation (FS/19/42/34527)
British Heart Foundation (PG/12/34/29557)
External DOI: https://doi.org/10.7554/eLife.70153
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330830