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

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 alpha(2c) 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.

Automated summary

Ageing is associated with increased vulnerability to environmental cold exposure, leading to impaired behavioural and vascular responses to skin local environmental cooling in aged mice. The decline in TRPM8 gene/protein expression in ageing mice suggests a reliance on remaining TRP receptor activity for cold-induced vascular response. Sympathetic-induced vasoconstriction is also reduced with aging, indicating a decline in the cold-induced vascular response necessary for maintaining body heat and health.