The Role of Cellular Senescence in Oral Health and Disease.

Cellular senescence is a fundamental biological process characterized by stable cell cycle arrest, resistance to apoptosis, and the acquisition of a pro-inflammatory senescence-associated secretory phenotype (SASP). While senescence plays essential roles in development, tissue homeostasis, and tumor suppression, its accumulation with age and chronic stress contributes to tissue dysfunction and disease. In the oral cavity, where tissues are continuously exposed to mechanical stress, microbial challenge, and environmental insults, senescence has emerged as a critical regulator of both health and pathology. This review provides an overview of the defining hallmarks of cellular senescence, the molecular mechanisms driving its onset, and its physiological and pathological consequences, with a particular focus on oral tissues. We highlight the beneficial roles of senescence in maintaining oral tissue integrity, facilitating wound repair, suppressing malignant transformation, and promoting immune-mediated clearance of damaged cells. Conversely, we discuss the detrimental effects of persistent senescent cell accumulation, including oral aging phenotypes, chronic inflammation, alveolar bone loss, periodontal breakdown, salivary gland dysfunction, and contributions to oral carcinogenesis. Finally, we examine emerging therapeutic strategies targeting senescence in oral disease management, including senolytic and senomorphic approaches, immune-based clearance mechanisms, and gene- and cell-based interventions aimed at delaying or modulating senescence. Understanding the dualistic nature of cellular senescence in the oral environment may inform novel preventive and therapeutic strategies to promote oral health and mitigate age- and disease-associated oral pathologies.