The Mediating Role of Biological Age Advance in the Association Between Periodontitis and Mortality: Biological Aging Links Periodontitis to Mortality.

Moderate/severe periodontitis was associated with a significantly elevated all-cause mortality risk compared to no/mild periodontitis.

• All-cause mortality rate was 18.31% in the moderate/severe periodontitis group versus 10.88% in the no/mild periodontitis group.
• Data were drawn from six cycles of National Health and Nutrition Examination Survey (NHANES) with a mortality follow-up of 250 months.
• Kaplan-Meier analysis was used to evaluate periodontitis-mortality associations.
• Cox proportional hazards models integrated with restricted cubic splines were utilized to explore associations.

Moderate/severe periodontitis was associated with greater biological age advancement compared to no/mild periodontitis.

• PhenoAge advancement was 1.22 years greater in the moderate/severe periodontitis group.
• KDM (Klemera-Doubal Method) biological age advancement was 0.68 years greater in the moderate/severe periodontitis group.
• Generalized linear models were used to examine the links between periodontitis and biological aging.
• Two distinct biological age measures (PhenoAge and KDM) were employed to assess biological aging.

Biological age acceleration exhibited a non-linear association with mortality, with hazard ratios rising sharply beyond specific threshold values.

• For PhenoAge, the threshold beyond which hazard ratios rose sharply was 16.4 years of advance.
• For KDM, the threshold beyond which hazard ratios rose sharply was 31.8 years of advance.
• The non-linear association was identified using Cox proportional hazards models integrated with restricted cubic splines.

Biological age partially mediated the association between periodontitis and all-cause mortality.

• The indirect effect hazard ratio for PhenoAge advance in all-cause mortality was 1.085 (95% CI: 1.067–1.106).
• The indirect effect hazard ratio for KDM advance in all-cause mortality was 1.027 (95% CI: 1.016–1.040).
• The proportion mediated was described as modest and varied across subgroups.
• Mediation analyses were used to quantify the mediating role of biological aging.
• Both measures indicated statistically significant partial mediation, as the confidence intervals excluded 1.0.

The mediating role of biological age in the periodontitis-mortality association varied across subgroups defined by age, gender, and smoking status.

• Subgroup analyses were conducted for age, gender, and smoking status.
• The proportion of the periodontitis-mortality association mediated by biological age advance was described as varying across these subgroups.
• Both PhenoAge and KDM were used as biological aging measures in subgroup analyses.