Targeting <scp>ATF6α</scp> Attenuates <scp>UVB</scp>‐Induced Senescence and Improves Skin Homeostasis by Regulating <scp>IL8</scp> Expression
Skin aging is influenced by both intrinsic and extrinsic factors, particularly UV radiation, and is characterized by an accumulation of senescent cells. Remarkably, exposure to UV can trigger senescence in different skin cell types, including dermal fibroblasts. However, the molecular mechanisms underlying UV-induced senescence and the impact of the related senescence-associated secretory phenotype (SASP) on the homeostasis of the overlying epidermis remain poorly understood. Here, we identified that both chronological aging and photoaging induce the unfolded protein response (UPR) in human dermal samples. We demonstrated that silencing ATF6α disrupts the establishment of the UVB-induced senescent phenotype by preventing the onset of several senescent biomarkers and alters the composition of the SASP, consequently affecting its impact on the increased proliferation of keratinocytes embedded in reconstructed human epidermis. Moreover, we found that ATF6α partially mediates IL8 expression involved in the hyperproliferation of cultured keratinocytes. Together, our findings highlight the importance of the ATF6α/IL8 axis in regulating the homeostasis of neighboring cells during skin photoaging, thus suggesting ATF6α as a potentially promising target for senotherapeutic interventions.
Authors
- Raphaël Rouget (ORCID: https://orcid.org/0000-0002-0751-8510)
- Clémentine de Schutter (ORCID: https://orcid.org/0000-0001-6670-1481)
- Yves Poumay (ORCID: https://orcid.org/0000-0001-5200-3367)
- Corinne Abbadie (ORCID: https://orcid.org/0000-0002-8174-2393)
- Nicolas Penel (ORCID: https://orcid.org/0000-0001-5243-1548)
- Gauthier Decanter (ORCID: https://orcid.org/0000-0001-9351-9861)
- Julien Théry (ORCID: https://orcid.org/0000-0001-9783-5925)
- Valérie De Glas (ORCID: https://orcid.org/0000-0001-7366-2601)
- Laurence Carlier (ORCID: https://orcid.org/0000-0001-5652-7942)
- Florence Debacq‐Chainiaux (ORCID: https://orcid.org/0000-0003-3949-395X)
- Ayeh Bolouki (ORCID: https://orcid.org/0000-0001-5920-3783)
- Benjamin Ledoux (ORCID: https://orcid.org/0009-0004-0336-6478)
- Sophie Burteau (ORCID: https://orcid.org/0000-0002-7191-2061)
- Yvan de Launoit (ORCID: https://orcid.org/0000-0003-1837-9808)
- Inès Bouriez (ORCID: https://orcid.org/0000-0001-7821-0444)
- Olivier Pluquet (ORCID: https://orcid.org/0000-0001-5178-0076)
- Pauline Delvaux
- Florent Bourdoux
- Joëlle Giroud (ORCID: https://orcid.org/0009-0006-6401-0605)
- Nathalie Martin (ORCID: https://orcid.org/0000-0003-1544-5347)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Namur (BE)
- Inserm (FR)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- Centre de Recherche en Automatique de Nancy (FR)
- Centre Oscar Lambret (FR)
- Université de Lorraine (FR)
Publication Details
- Journal
- Aging Cell
- Published
- 2025-04-16
- DOI
- https://doi.org/10.1111/acel.70024
- Citations
- 2
- Primary Topic
- Skin Protection and Aging
- Type
- article
- Field-Weighted Citation Impact
- 4.01
Funders
- Université de Lille
- Institut National de la Santé et de la Recherche Médicale
- Fonds De La Recherche Scientifique - FNRS
- Ministère de l'Enseignement Supérieur et de la Recherche Scientifique
- Ministère de l'Europe et des Affaires Étrangères
- Ligue Contre le Cancer
- Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche
- Centre National de la Recherche Scientifique
- Institute Pasteur De Lille
- Université de Namur