Aging-Associated Failure of Inflammation Resolution in Periodontal Disease: Macrophages at the Crossroads of Chronic Inflammation and Tissue Repair

<jats:p>Periodontitis is a chronic inflammatory disease in which dysregulated host responses to the oral microbial biofilm drive destruction of periodontal connective tissue and alveolar bone. Increasing evidence indicates that chronic periodontal inflammation may reflect not only excessive inflammatory activation but also a failure of active inflammation resolution. Aging may further increase susceptibility to periodontal tissue damage by promoting inflammaging, altering immune cell function, and impairing tissue repair. Among the immune cells involved in periodontal inflammation, macrophages are particularly important because they coordinate inflammatory responses, efferocytosis, tissue remodeling, and restoration of tissue homeostasis. However, how aging alters the resolution-associated functions of periodontal macrophages remains incompletely understood. In this review, we integrate emerging evidence from periodontal disease, aging biology, macrophage immunology, and specialized pro-resolving mediator (SPM) research to propose a framework linking aging-associated macrophage dysfunction to impaired periodontal inflammation resolution and tissue repair. We discuss evidence that aged periodontal tissues exhibit altered inflammatory responses and macrophage-dependent recovery, while SPMs—including resolvins, maresins, protectins, and lipoxins—can promote resolution, regulate macrophage functions, and protect periodontal tissues in experimental models. We further consider how impaired efferocytosis, persistent inflammatory signaling, and altered tissue-remodeling programs may contribute to an age-associated failure of periodontal repair. Importantly, the available literature supports the individual components of this model but has not yet established a complete causal pathway connecting aging, periodontal macrophage resolution dysfunction, and impaired regeneration. We therefore identify macrophage resolution capacity as a potential mechanistic and therapeutic interface between aging and periodontal disease and discuss how SPM-based approaches may provide a strategy to restore inflammatory resolution and promote periodontal tissue repair.</jats:p>