Cellular senescence and the SASP in the oral-metabolic axis: a putative link between periodontitis and type 2 diabetes mellitus.

Periodontitis and type 2 diabetes mellitus (T2DM) are chronic inflammatory disorders with a bidirectional clinical association. Although microbial, immune, and metabolic mechanisms contribute to this relationship, they do not fully explain the persistence of inflammation and defective tissue repair. Cellular senescence and the senescence-associated secretory phenotype (SASP) may provide an additional framework for understanding this interaction. Within periodontal tissues, sustained microbial and metabolic stress may promote senescence-associated changes that disturb local immune regulation, tissue regeneration and bone homeostasis. These processes could interact with microbial dysbiosis and systemic inflammation as part of the oral-metabolic axis. However, the available evidence remains uneven. Diabetes-related stress can promote senescence-like changes in periodontal tissues, whereas direct evidence that periodontal senescence impairs distant metabolic organs is limited. This review examines the evidence linking cellular senescence to periodontal inflammation and T2DM, and discusses the emerging preclinical evidence for targeting senescent cells and the SASP.