Cellular senescence in giant cell arteritis and polymyalgia rheumatica: From mechanisms to therapeutic opportunities.

BACKGROUND

Giant cell arteritis (GCA) and (PMR) are inflammatory rheumatic disorders whose pathogenesis are unclear. The interleukin (IL)-6 receptor inhibitor is the first approved biologic agent for GCA and PMR, reducing relapse rates and cumulative glucocorticoid (GC) doses. Notably, IL-6, also a key pro-inflammatory factor secreted by senescent cells, contributes to tissue aging and chronic inflammation. We aim to explore the role of senescence-associated secretory phenotype (SASP) in the pathogenesis of GCA and PMR.

METHODS

A narrative synthesis of literature published in the last 10 years was conducted utilizing keywords such as "Giant cell arteritis," "Polymyalgia rheumatica," "cellular senescence," "senescence-associated secretory phenotype," or "aging".

RESULTS

Evidence links cellular senescence and SASP to the pathogenesis of GCA and PMR, with key components like IL-6, IL-1β, and matrix metalloproteinases (MMPs) driving inflammation and tissue damage. We highlight how key SASP components, such as IL-6, IL-1β, and MMPs promote inflammation and tissue damage in GCA and PMR. Targeting SASP factors (senomorphics) or selectively eliminating senescent cells (senolytics) offers therapeutic potential. Further research into the mechanisms linking senescence to disease phenotypes is needed to develop effective therapies that mitigate disease progression and improve clinical outcomes.

CONCLUSION

We demonstrated age-related stress and senescence in the pathogenesis of GCA and PMR. We provide an overview of senomorphics, which have shown promise in clinical trials, and emphasize the need for further research to develop effective therapies.