From senescence and inflammaging to systemic comorbidities: Drivers of aging‐associated periodontitis

BACKGROUND: Aging is accompanied by a chronic low-grade inflammatory process, known as inflammaging, as well as immunosenescence, an age-related decline and dysregulation of immune function, and cellular senescence, a process in which cells enter a state of irreversible growth arrest while actively releasing pro-inflammatory factors. These processes alter the host immune regulation and tissue homeostasis. Aging-associated mechanisms are being explored for their role in periodontal and peri-implant diseases because of their promotion of dysregulated inflammation, impaired healing, and heightened susceptibility to tissue destruction. Rather than viewing periodontitis as a condition driven solely by microbial burden, it should be understood as a multifactorial disease shaped by complex host-microbe interactions, in which host-driven processes, particularly senescence and inflammaging, play a central role in amplifying bidirectional oral-systemic interactions. AIM: This scoping review aims to (i) highlight the current understanding of the role of aging and its alterations in host inflammatory responses on immune function, tissue homeostasis, and cellular stress responses; (ii) explore the potential impact of "inflammaging" on the periodontium and interactions with systemic health; and (iii) explore possible therapeutic targets for senotherapy. MATERIALS AND METHODS: A literature search of the PubMed database was conducted using Boolean search strategies to identify publications related to the potential connections between aging and inflammation in the context of the oral cavity. RESULTS: Of the total 283 articles that were screened, 87 met the eligibility criteria and were included in this scoping review. An additional 51 articles were obtained via manual search. The evidence demonstrates a link between inflammaging, age-related cellular senescence, and periodontal vulnerability to periodontal pathogens and periodontal destruction. Both experimental and clinical studies have shown increased senescence markers, dysregulated immune responses, and enhanced osteoclastic activity that lead to greater tissue destruction and alveolar bone loss. Systemic conditions such as Alzheimer's disease, diabetes, and cardiovascular disease can also amplify the inflammatory burden through shared pathways. Overall, our findings support the idea that older adults undergo immune dysregulation when challenged with microbes that ultimately cause a chronic periodontal inflammatory state.