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Aging is associated with impaired triggering of TRPV3-mediated cutaneous vasodilation: a crucial process for local heat exposure

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Abstract

Sensing temperature is vitally important to adapt our body to environmental changes. Local warm detection is required to initiate regulation of cutaneous blood flow, which is part of the peripheral thermoregulatory mechanisms, and thus avoid damage to surrounding tissues. The mechanisms mediating cutaneous vasodilation during local heat stress are impaired with aging. However, the impact of aging on the ability of the skin to detect subtle thermal changes is unknown. Among heat-activated cation channels, transient receptor potential vanilloid 3 (TRPV3) is a thermo-sensor predominantly expressed on keratinocytes and involved in local vascular thermoregulatory mechanisms of the skin in young mice. In the present study, using a murine in vivo model of local heat exposure of the skin, we showed that heat-induced vasodilation was reduced in old mice associated with reduced expression of TRPV3 channels. We also found a decrease in expression and activity of TRPV3 channel, as well as reduced TRPV3-dependent adenosine tri-phosphate release in human primary keratinocytes from old donors. This study shows that aging alters the epidermal TRPV3 channels, which might delay the detection of changes in skin temperature, thereby limiting the mechanisms triggered for local vascular thermoregulation in the old skin.

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Acknowledgements

We acknowledge Jocelyne Vial and Geraldine Aimond for technical support and animal care facilities (AnexPeau facility, Lyon). We thank Theo Barthélemy and Emma Fraillon for their precious help for some experiments. We also thank Nicolas Lebonvallet, Ophelie Pierre, and Laurent Misery for their support and access to the calcium imaging platform of Laboratoire Interactions Epitheliums Neurones (LIEN/EA 4685/Brest). We thank Fabien Van Coppenolle (CarMeN/INSERM, U1060/Lyon) for his help in calcium imaging analysis and discussion. We thank PLATIM and especially Elodie Chatre for the microscopy. We thank Jerome Lamartine for critical reading of the manuscript.

Funding

This research project was supported by internal funds from CNRS and University Lyon 1. This work was supported by the French National Research Agency (KAST-ANR-23-CE14-0015).

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Author notes

  1. Fabien P. Chevalier and Bérengère Fromy contributed equally to this work.

Authors and Affiliations

  1. CNRS UMR 5305, Tissue Biology and Therapeutic Engineering Laboratory (LBTI), 69007, Lyon, France

    Lisa S. Martin, Audrey Josset-Lamaugarny, Thomas El Jammal, Fabien P. Chevalier & Bérengère Fromy

  2. Claude Bernard University Lyon 1, 69100, Villeurbanne, France

    Lisa S. Martin, Audrey Josset-Lamaugarny, Thomas El Jammal, Fabien P. Chevalier & Bérengère Fromy

  3. Department of Internal Medicine, University Hospital Lyon Croix-Rousse, Claude Bernard University Lyon 1, Lyon, France

    Thomas El Jammal

  4. CarMeN Laboratory, INSERM, INRA, INSA Lyon, Claude Bernard University Lyon 1, 69500, Bron, France

    Sylvie Ducreux

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Contributions

Conceptualization, L.S.M., F.P.C., and B.F.; methodology, L.S.M., A.J.-M., S.D., F.P.C., and B.F.; validation, L.S.M., T.E.J., F.P.C., and B.F.; formal analysis, L.S.M., A.J.-M., S.D., T.E.J., F.P.C., and B.F.; investigation, L.S.M., A.J.-M., S.D., F.P.C., and B.F.; resources, L.S.M., S.D., F.P.C., and B.F.; writing—original draft preparation, L.S.M., F.P.C., and B.F.; writing—review and editing, L.S.M., F.P.C., and B.F.; visualization, L.S.M., F.P.C., B.F.; S.D., T.E.J.; supervision, F.P.C. and B.F.; project administration, F.P.C. and B.F.; funding acquisition, F.P.C. and B.F.; all authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Bérengère Fromy.

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The animal study protocol was approved by the Animal Experimentation Committee of the University Claude Bernard Lyon I (protocol agreement #33946 approved on 25 November 2021).

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Skin biopsies were obtained from the DermoBioTec tissue bank at Lyon (Tissue Transfer Agreement n_214854) with the informed consent of adult donors undergoing surgical discard (non-pathological tissues from breast, face, or abdomen), in accordance with the ethical guidelines (French Bioethics law of 2021).

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The authors declare no competing interests.

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Martin, L.S., Josset-Lamaugarny, A., El Jammal, T. et al. Aging is associated with impaired triggering of TRPV3-mediated cutaneous vasodilation: a crucial process for local heat exposure. GeroScience (2023). https://doi.org/10.1007/s11357-023-00981-5

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  • DOI: https://doi.org/10.1007/s11357-023-00981-5

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