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Barbera, MC, Guarrera, L, Re Cecconi, AD, Cassanmagnago, GA, Vallerga, A, Lunardi, M, Checchi, F, Di Rito, L, Romeo, M, Mapelli, SN, Schoser, B, Generozov, EV, Molecular Genetics Group, , Jansen, R, de Geus, EJC, Penninx, B, van Dongen, J, Craparotta, I, Piccirillo, R, Ahmetov, II and Bolis, M (2025) Increased ectodysplasin-A2-receptor EDA2R is a ubiquitous hallmark of aging and mediates parainflammatory responses. Nature Communications, 16. pp. 1-11. ISSN 2041-1723
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Increased ectodysplasin A2receptor EDA2R is a ubiquitous hallmark of aging and mediates parainflammatory responses.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
Intensive efforts have been made to identify features that could serve as biomarkers of aging. Yet, drug-based interventions aimed at lessening the detrimental effects of getting older are lacking. This is largely attributable to tissue-specificity, sex-related differences, and to the difficulty of identifying actionable targets, which continues to pose a significant challenge. Here, we implement a bioinformatics approach revealing that aging-associated increase of the transmembrane Ectodysplasin-A2-Receptor is a prominent tissue-independent alteration occurring in humans and other species, and is particularly pronounced in models of accelerated aging. We show that strengthening of the Ectodysplasin-A2-Receptor signalling axis in myogenic precursors and differentiated myotubes suffices to trigger potent parainflammatory responses, mirroring aspects of aging-driven sarcopenia. Intriguingly, obesity, insulin-resistance, and aging-related comorbidities, such as type-2-diabetes, result in heightened levels of the Ectodysplasin-A2 ligand. Our findings suggest that targeting the Ectodysplasin-A2 surface receptor represents a promising pharmacological strategy to mitigate the development of aging-associated phenotypes.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > RC Internal medicine > RC1200 Sports Medicine R Medicine > RS Pharmacy and materia medica |
| Divisions: | Sport and Exercise Sciences |
| Publisher: | Nature Publishing Group |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 24 Feb 2025 12:06 |
| Last Modified: | 24 Feb 2025 12:15 |
| DOI or ID number: | 10.1038/s41467-025-56918-3 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/25703 |
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