Association between DNA methylation-based aging clocks and periodontitis in aged adults: results from NHANES 1999–2002

Background DNA methylation aging clocks reflect biological aging, but their relationship with periodontitis has not been systematically evaluated. This study aimed to compare first- and second-generation DNA methylation clocks to identify the optimal epigenetic aging biomarker for periodontitis.Methods We analyzed 1,559 adults (aged ≥50 years) from the NHANES database (1999–2002) using logistic regression, subgroup analysis, restricted cubic spline, and receiver operating characteristic analysis.Results Higher quartiles of DNA methylation-based aging measures showed increased odds of periodontitis: PhenoAge (ORquartile4vs1 = 2.507, 95% CI: 1.181–5.324) and GrimAge2 (ORquartile4vs1 = 2.796, 95% CI: 1.093–7.154). Similar trends occurred for age acceleration measures, PhenoAgeAccel (ORquartile4vs1 = 1.958, 95% CI: 1.039–3.689) and GrimAge2Accel (ORquartile4vs1 = 2.667, 95% CI: 1.238–5.748). GrimAge2 demonstrated moderate discriminative ability (AUC = 0.700), which was the highest among the clocks assessed.Conclusion Second-generation DNA methylation clocks, particularly PhenoAge and GrimAge2, were positively associated with periodontitis in older adults.