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Features of immune system aging can be detected in the earliest stages of rheumatoid arthritis (RA), even before clinical diagnosis, a new study has found which provides at-risk individuals with hope for early intervention.

The research led by academics at the University of Birmingham and published in the journal eBioMedicine shows that individuals with joint pain or undifferentiated arthritis already exhibit signs of a prematurely aged immune system, suggesting that immune aging may play a direct role in the development of RA.

The study involved 224 participants across various stages of RA development. It represents one of the most comprehensive analyses of immune aging in RA to date.

Researchers found that patients with early immune aging features were more likely to develop RA. These findings could lead to the development of predictive tools that identify at-risk individuals and enable timely treatment.

"We've discovered that immune aging isn't just a consequence of rheumatoid arthritis—it may be a driver of the disease itself, " said Dr. Niharika Duggal, senior author of the study and Associate Professor in Immune Aging at the University of Birmingham. "We found that people in the early stages of rheumatoid arthritis, i.e. before a clinical diagnosis, show signs of faster immune system aging.

CD4 T cell subset distribution across disease phases leading up to the development of Rheumatoid Arthritis. Credit: eBioMedicine (2025). DOI: 10.1016/j.ebiom.2025.105900

"These findings suggest we might be able to intercept the disease development in at-risk individuals and prevent it from developing by using treatments that slow aging, such as boosting the body's natural process for clearing out damaged cells (autophagy)."

Key findings include:

The study suggests that targeting aging pathways could offer new strategies to prevent RA. Future research should determine whether geroprotective drugs such as spermidine (autophagy booster), senolytics (clearance of senescent cells) and metformin (attenuates inflammation and boosts autophagy) may help slow or halt disease progression in high-risk individuals.

More information: Karim Raza et al, Specific features of immune ageing are detected in the earliest stages in rheumatoid arthritis development, eBioMedicine (2025). DOI: 10.1016/j.ebiom.2025.105900  Journal information: EBioMedicine