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New IOR Study Identifies EDA2R as a Universal Biomarker of Aging and a Driver of Parainflammation

Institutional Communication Service

A new study from the IOR Bioinformatics Unit, published in Nature Communications, has identified the Ectodysplasin-A2 Receptor (EDA2R) as a tissue-independent biomarker of aging and a key mediator of chronic inflammatory responses linked to age-related diseases. Led by Marco Bolis, PhD, the research provides novel insights into the molecular mechanisms that drive aging and suggests new potential therapeutic strategies.

Aging is a complex biological process that affects multiple tissues and is closely associated with increased inflammation and the development of metabolic disorders. Using advanced bioinformatics and multi-species transcriptomic analysis, the IOR research team demonstrated that EDA2R expression consistently rises with age across various tissues in humans and other species. This increase was particularly pronounced in models of accelerated aging, reinforcing its role as a conserved signature of the aging process.

Beyond its correlation with aging, the study also provides functional evidence that heightened EDA2R signaling in muscle cells induces a parainflammatory state, characterized by the activation of pro-inflammatory cytokines and immune mediators. Notably, this inflammatory response mimics features of sarcopenia, a condition of muscle loss and weakness that occurs with aging. Moreover, the study highlights that conditions such as obesity, insulin resistance, and type 2 diabetes are associated with elevated levels of EDA-A2, the ligand that activates EDA2R, suggesting a broader role for this pathway in aging-related comorbidities.

"Our findings have identified EDA2R as a robust, tissue-independent marker of aging and revealed its role as a mediator of chronic inflammatory responses," explains Marco Bolis, PhD, lead author of the study. "This research paves the way for developing targeted therapies aimed at modulating EDA2R signaling to mitigate aging-associated conditions."

The study underscores the potential of EDA2R-targeted interventions in reducing inflammation and improving healthy aging. Given the absence of specific EDA2R inhibitors currently available, further research is needed to explore pharmacological strategies to modulate this pathway. The IOR Bioinformatics Unit will continue its investigations into the therapeutic implications of EDA2R in collaboration with international partners.

This work reinforces IOR's commitment to pioneering bioinformatics-driven discoveries in aging and molecular medicine.

For more details, the full study is available in Nature Communications: https://doi.org/10.1038/s41467-025-56918-3.