“Inflammation” Gene Linked to Faster Aging

New therapies for managing ageing could emerge from research into a new gene, which scientists have identified as a key driver of degeneration.

Age-related diseases are strongly linked to inflammation which when chronic, albeit low-grade, contributes to conditions such as cardiovascular disease, diabetes, neurodegeneration, and sarcopenia, significantly impacting health and longevity.

In a study published in Nature Communications, Dr Ildus Akhmetov, a geneticist at Liverpool John Moores University’s School of Sport and Exercise Sciences, along with colleagues from Italy, Switzerland, and the Netherlands, uncovered groundbreaking insights into the role of the Ectodysplasin A2 Receptor (EDA2R) in this process.

EDA2R, a member of the tumour necrosis factor receptor family, specifically binds to the EDA-A2 protein and is involved in apoptosis, or cell death, and inflammatory signalling.

By analysing data from the Genotype-Tissue Expression database, the team identified a striking, tissue-independent correlation between EDA2R expression and age. Across diverse human organs and tissues, EDA2R consistently emerged as the top gene associated with ageing.

These findings were further validated in rodent models, with particularly pronounced effects of accelerated ageing. Elevated EDA2R expression was linked to transcriptional changes associated with inflammation and vascular dysfunction—hallmarks of ageing.

The team reveal the gene as a biomarker of inflammation and potential driver of the ageing process itself

However, Dr Akhmetov’s team revealed that EDA2R functions not only as a biomarker of chronic inflammation but also as a potential driver of the ageing process itself. In cellular models, EDA2R overexpression triggered inflammatory signalling and disrupted muscle health pathways, mimicking key features of aging-driven sarcopenia, the progressive loss of muscle mass and strength. Conversely, EDA2R inhibition mitigated these detrimental effects.

To extend their analysis, the team examined blood samples from 5,228 individuals, revealing a strong correlation between EDA2R expression and systemic inflammation, as indicated by elevated C-reactive protein levels.

Dr Akhmetov, one of the study’s senior authors, said: “These findings suggest that the EDA2R/EDA-A2 axis may play a pivotal role in mediating age-related inflammatory and degenerative processes across tissues.

“Targeting EDA2R could open new therapeutic avenues for managing aging-related conditions, including sarcopenia, cardiovascular disease, neurodegeneration, and metabolic disorders.

“Our work has laid a strong foundation for future research aimed at developing interventions to modulate EDA2R signalling and reduce the impact of aging.”

And he said there was already evidence that reducing EDA2R levels could be beneficial.

“The literature and our preliminary data indicate that calorie restriction, physical activity, the dietary supplement ginkgo, and the widely prescribed glucose-regulating medication metformin can reduce EDA2R levels in animal models and human subjects.

“This suggests a promising strategy for mitigating ageing-related inflammatory processes and enhancing overall health outcomes.”

Reference: Barbera MC, Guarrera L, Re Cecconi AD, et al. Increased ectodysplasin-A2-receptor EDA2R is a ubiquitous hallmark of aging and mediates parainflammatory responses. Nat Commun. 2025;16(1):1898. doi: 10.1038/s41467-025-56918-3

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