Immunosenescence in Autoimmune Rheumatic Diseases: Mechanisms, Clinical Consequences, Biomarkers, and Emerging Therapeutic Strategies

Abstract

Immune senescence has emerged as one of the principal biological mechanisms linking aging with the development and progression of autoimmune rheumatic diseases. Rather than representing a simple decline in immune function, aging induces profound remodeling of both innate and adaptive immunity, characterized by chronic low-grade inflammation, loss of immune tolerance, impaired cellular regeneration, mitochondrial dysfunction, telomere shortening, epigenetic alterations, and expansion of senescent immune-cell populations. The objective of this review was to analyze current evidence regarding the mechanisms through which immune senescence reshapes autoimmune rheumatic diseases and to examine its clinical implications, biomarkers, and emerging therapeutic strategies. A narrative literature review was conducted using the scientific method and included publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, SpringerLink, Nature, Frontiers, and Wiley. The evidence consistently demonstrated that inflammaging, adaptive immune remodeling, and cellular senescence contribute to disease progression, increased susceptibility to infections, reduced vaccine responsiveness, cardiovascular complications, frailty, osteoporosis, sarcopenia, and diminished functional capacity. Conventional inflammatory biomarkers remain widely used; however, increasing attention has been directed toward multi-omics technologies, epigenetic clocks, mitochondrial biomarkers, proteomics, metabolomics, and immune-cell phenotyping for more accurate assessment of biological immune aging. Current therapeutic approaches continue to rely on disease-modifying antirheumatic drugs and biologic agents, while emerging interventions—including JAK inhibitors, mTOR modulation, senolytic therapies, microbiome-targeted strategies, and precision medicine—offer promising opportunities for future individualized management. Overall, immune senescence should be recognized as a fundamental component of autoimmune rheumatic diseases, providing important opportunities for improving diagnosis, risk stratification, therapeutic decision-making, and long-term clinical outcomes in aging populations.