Immunological consequences of senescence in physiology and pathology

BACKGROUND: Cellular senescence is a sublethal stress response characterized by a durable cell-cycle arrest and the acquisition of a complex secretory program known as the senescence-associated secretory phenotype (SASP), which can profoundly influence local and systemic immunity. In physiological contexts-including embryonic development, tissue repair, and acute tumour suppression-senescent cells coordinate the recruitment and activation of immune cells, enabling their timely immune-mediated clearance and facilitating tissue remodelling and restoration of homeostasis. However, during aging and chronic disease, immune surveillance mechanisms frequently become compromised, allowing senescent cells to accumulate and persist within tissues. MAIN BODY: The persistence of senescent cells results in sustained SASP signalling that promotes chronic inflammation, immune dysfunction, and tissue remodelling processes linked to fibrosis, metabolic impairment, tumour progression, and defective tissue repair. In parallel, increasing evidence indicates that immune cells themselves can acquire senescent or senescence-like states, thereby weakening immunosurveillance and generating self-reinforcing feedback loops that further amplify senescent cell accumulation and tissue dysfunction. In this review, we synthesize recent advances in understanding the bidirectional interactions between senescent cells and the immune system across physiological and pathological contexts, with particular emphasis on the mechanisms that govern immune recognition, clearance, and immune evasion. CONCLUSIONS: A deeper understanding of the reciprocal interplay between senescent cells and the immune system provides an important conceptual framework for the development of new therapeutic strategies. Interventions aimed at modulating senescence-immune crosstalk - including immune-mediated senolytic approaches, checkpoint modulation, and immune rejuvenation - may offer promising opportunities to restore immune surveillance, limit the detrimental consequences of persistent senescence, and ultimately improve outcomes in age-related diseases.