Immunosenescence in systemic lupus erythematosus: Mechanisms, clinical consequences, and therapeutic implications

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with chronic immune dysregulation across the lifespan. Accumulating evidence suggests that many immunological alterations observed in SLE resemble those seen in physiological aging. Here, we review the major innate and adaptive mechanisms of immunosenescence in SLE, including telomere shortening, chronic low-grade inflammation, thymic dysfunction, and the expansion of senescent immune cell subsets. Of note, we discuss how these age-associated immune phenotypes emerge early and contribute to disease activity, organ damage, and long-term outcomes. Clinically, immunosenescence contributes to cardiovascular complications, frailty, increased infections, and cognitive impairment in SLE. Therapies targeting senescence-related pathways - including modulation of intracellular metabolic pathways and senolytics - are also discussed and constitute promise as emerging strategies.