Background: Infectious diseases contribute substantially to morbidity and mortality among aging populations, yet the impact of biological aging on severe infection risk remains unclear.
Methods: Cox proportional hazards models estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations of accelerated biological aging (measured by KDM-BA and PhenoAge) and frailty index (FI) with overall and type-specific severe infections. Life expectancy differences by biological aging status were assessed. Bivariate response surface models evaluated combined effects of FI and two biological age acceleration indicators on severe infections.
Results: KDM-BA acceleration (HR: 1.18; 95 % CI: 1.16 to 1.19) and PhenoAge acceleration (HR: 1.27; 95 % CI: 1.25 to 1.29) were associated with increased severe infection risk. Higher FI levels showed progressively greater risk, with HRs (95 % CIs) of 1.40 (1.38 to 1.43), 2.01 (1.96 to 2.06), 2.64 (2.53 to 2.76) and 3.37 (2.96 to 3.83) for FI categories 0.1 -< 0.2, 0.2 -< 0.3, 0.3 -< 0.4, and ≥ 0.4 versus FI < 0.1. Associations varied by infection type: KDM-BA acceleration and PhenoAge acceleration showed the strongest associations with respiratory infections, whereas the frailty index was most associated with digestive infections. Significant combined effects of FI and biological age accelerations further increased risk. Biologically younger individuals had longer life expectancy: +1.59 years (95 % CI: 1.40 to 1.77) for KDM-BA acceleration and +2.2 years (95 % CI: 2.00 to 2.40) for PhenoAge acceleration.
Conclusion: Accelerated biological aging and frailty were significantly associated with increased risks of overall and type-specific severe infections. These findings suggest that integrating biological aging assessments into routine healthcare could improve infection risk stratification and guide targeted prevention strategies.
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