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dc.contributor.authorThapa, Dibesh
dc.contributor.authorValente, Joäo de Sousa
dc.contributor.authorBarrett, Brentton
dc.contributor.authorSmith, Matthew John
dc.contributor.authorArgunhan, Fulye
dc.contributor.authorLee, Sheng Y
dc.contributor.authorNikitochkina, Sofya
dc.contributor.authorKodji, Xenia
dc.contributor.authorBrain, Susan D
dc.date.accessioned2022-01-06T12:55:14Z
dc.date.available2022-01-06T12:55:14Z
dc.date.issued2021-11-02
dc.identifier.issn2050-084X
dc.identifier.otherPMC8592571
dc.identifier.other34726597
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332204
dc.description.abstractAgeing 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.
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2050-084X
dc.sourcenlmid: 101579614
dc.subjectBiochemistry
dc.subjectMouse
dc.subjectAgeing
dc.subjectThermoregulation
dc.subjectTrpm8
dc.subjectTrpa1
dc.subjectChemical Biology
dc.subjectCold Response
dc.subjectVascular Response
dc.titleDysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.
dc.typeArticle
dc.date.updated2022-01-06T12:55:13Z
prism.publicationNameElife
prism.volume10
dc.identifier.doi10.17863/CAM.79650
dcterms.dateAccepted2021-11-02
rioxxterms.versionofrecord10.7554/eLife.70153
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidThapa, Dibesh [0000-0002-7435-5483]
dc.contributor.orcidBrain, Susan D [0000-0002-9684-8342]
dc.identifier.eissn2050-084X
pubs.funder-project-idVersus Arthritis (ARUK21524)
pubs.funder-project-idBritish Heart Foundation (PG/12/34/29557, FS/19/42/34527)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P005616/1)
cam.issuedOnline2021-11-02


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International