Published on: Sep 08, 2025
A new study from the University of Birmingham has revealed that features of immune system ageing can be detected long before rheumatoid arthritis (RA) is clinically diagnosed, offering hope for early intervention in individuals at risk.
Published in eBioMedicine and funded by FOREUM and the European League Against Rheumatism (EULAR), the research analyzed 224 participants across different stages of RA development—making it one of the most comprehensive studies of immune ageing in the disease to date.
Key Discoveries
Premature immune ageing detected early: Individuals with joint pain or undifferentiated arthritis already showed signs of accelerated immune system ageing.
Higher risk of RA onset: Participants with early immune ageing features were more likely to progress to rheumatoid arthritis.
Distinct immune changes over time:
Pre-diagnosis stages revealed reduced naïve T cells, lower thymic output, and elevated inflammatory markers (IL-6, TNFα, CRP).
Advanced stages of RA were marked by senescent T cells and inflammatory Th17 cells.
Predictive potential: An elevated IMM-AGE score—a measure of immune ageing—helped identify those at greater risk of developing RA.
These findings show that immune ageing isn’t just a consequence of rheumatoid arthritis—it may actually drive the disease,said Dr. Niharika Duggal, Associate Professor in Immune Ageing at the University of Birmingham and senior author of the study. Importantly, even before diagnosis, patients already displayed signs of faster immune system ageing.
Future Implications
The research suggests that targeting ageing pathways could help delay or even prevent RA in high-risk individuals. Potential strategies include:
Boosting autophagy with compounds such as spermidine.
Senolytic therapies to clear damaged, senescent cells.
Metformin, which reduces inflammation while supporting healthy cell function.
By intervening early, researchers hope to transform how RA is managed—shifting from treatment after diagnosis to prevention at the earliest stages of disease development.
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