Increased ectodysplasin-A2-receptor EDA2R is a ubiquitous hallmark of aging and mediates parainflammatory responses

Maria Chiara Barbera, Luca Guarrera, Andrea David Re Cecconi, Giada Andrea Cassanmagnago, Arianna Vallerga, Martina Lunardi, Francesca Checchi, Laura Rito, Margherita Romeo, Sarah Natalia Mapelli, Benedikt Schoser, Edward V. Generozov, Rick Jansen, Eco J. C. Geus, Brenda Penninx, Jenny Dongen, Ilaria Craparotta, Rosanna Piccirillo, Ildus I. Ahmetov and Marco Bolis ()
Additional contact information
Maria Chiara Barbera: Via Mario Negri 2
Luca Guarrera: Via Mario Negri 2
Andrea David Re Cecconi: Via Mario Negri 2
Giada Andrea Cassanmagnago: Via Mario Negri 2
Arianna Vallerga: Via Mario Negri 2
Martina Lunardi: Via Mario Negri 2
Francesca Checchi: Via Mario Negri 2
Laura Rito: Via Mario Negri 2
Margherita Romeo: Via Mario Negri 2
Sarah Natalia Mapelli: IRCCS Humanitas Research Hospital
Benedikt Schoser: Ludwig-Maximilians University
Edward V. Generozov: Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
Rick Jansen: Amsterdam UMC location Vrije Universiteit Amsterdam
Eco J. C. Geus: Vrije Universiteit Amsterdam
Brenda Penninx: Amsterdam UMC location Vrije Universiteit Amsterdam
Jenny Dongen: Vrije Universiteit Amsterdam
Ilaria Craparotta: Via Mario Negri 2
Rosanna Piccirillo: Via Mario Negri 2
Ildus I. Ahmetov: Liverpool John Moores University
Marco Bolis: Via Mario Negri 2

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56918-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56918-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56918-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().