Periodontitis, Edentulism, and Accelerated Biological Aging: A Population-Based Study of Epigenetic Clocks.

AIM: To examine whether periodontitis and its ultimate sequela (edentulism) are associated with accelerated epigenetic aging in older adults. METHODS: A total of 1 926 adults aged ≥ 50 years with DNA-methylation (DNAm) and oral health data from the NHANES 1999-2002 cycles were included. Periodontitis (stages/grades) and edentulism were classified using the 2018 AAP/EFP framework via the ACES system. Epigenetic age acceleration was estimated using genome-wide DNAm for four clocks: HannumAge, HorvathAge, PhenoAge, and GrimAge2Mort. Survey-weighted linear regression models, adjusted for relevant confounders, assessed the relationship between periodontal status and epigenetic age acceleration. RESULTS: In fully adjusted models, Stage III-IV periodontitis was associated with higher biological age acceleration compared with healthy/gingivitis/Stage I for three of the four clocks examined: PhenoAge +2.12 years (95% CI 0.64-3.59), HannumAge +1.48 years (0.34-2.62), and GrimAge2Mort +1.35 years (0.52-2.63). Associations with edentulism were stronger in 3 of the clocks: HorvathAge +1.31 years (0.00-2.62), HannumAge +1.92 years (0.72-3.12), and GrimAge2Mort +1.77 years (0.90-2.65). Accelerated aging was also observed in individuals with Grade B/C periodontitis for HorvathAge (+1.04 years; 0.35-1.72), HannumAge (+0.93 years; 0.26-1.60), and GrimAge (+0.55 years; 0.03 = 1.07), when compared with health/gingivitis/Grade A. Associations were also observed between mean interproximal CAL and age acceleration in all four clocks. CONCLUSION: Severe and higher-grade periodontitis, as well as edentulism, are associated with higher epigenetic aging acceleration, suggesting that these oral conditions may reflect-or potentially contribute to-systemic biological aging.