Aging
Epigenetic aging mediates the association between oral health and mortality in the United States Hyeji Seo* Hyeji Seo Seo Seo Seo Department of Social and Preventive Medicine, Sungkyunkwan University School of Medicine
Periodontitis and tooth loss are linked to mortality, but the role of epigenetic aging in this relationship remains unclear. This study investigated the associations of oral health with DNA methylation-based epigenetic age acceleration (EAA) and evaluated whether EAA mediates the link between oral health and mortality.
We analyzed data from 1,764 participants from the National Health and Nutrition Examination Survey (1999-2002) and linked mortality data from the National Death Index up to December 2019 (median follow-up: 17.4 years; IQR: 10.4, 18.8). Periodontitis severity was classified as mild, moderate or severe based on CDC/AAP definitions. Number of teeth was categorized into four groups: ≥ 20, 10–19, 1–9 and 0 (edentulous). Seven EAA measures were examined: IEAA, EEAA, PhenoAA, SBAA, GrimAA, Grim2AA and DunedinPoAm. We evaluated the associations using multivariable linear and Cox proportional hazards models, and assessed the mediating role of EAA adjusting for demographic characteristics, lifestyle behaviors, and anthropometric parameters.
Participants with periodontitis exhibited higher EAA across all measures except IEAA compared to those without periodontitis (b range: 0.897–1.902, all p < 0.05). Similarly, compared to those with ≥ 20 teeth, individuals with < 20 teeth showed higher EAA (b: 1.164 [95% CI: 0.29, 2.038] for Grim2AA; b: 1.051 [0.206, 1.896] for GrimAA). Mediation analyses revealed that Grim2AA partially mediated the association between tooth loss and mortality, accounting for 29.0% of all-cause mortality (95% CI: 13.0, 68.9), 19.8% of CVD mortality (2.0, 97.5), and 23.1% of lower respiratory disease mortality (8.6, 51.0). However, no mediation was observed for periodontitis.
Epigenetic age acceleration, particularly Grim2AA, serves as a key biological mechanism linking tooth loss to increased mortality risk. Our findings suggest that maintaining optimal oral health may be crucial for slowing biological aging and promoting longevity.