All-Subset Analysis Improves the Predictive Accuracy of Biological Age for All-Cause Mortality in Chinese and U.S. Populations

Klemera-Doubal's method (KDM) is an advanced and widely applied algorithm for estimating biological age (BA), but it has no uniform paradigm for biomarker processing. This article proposed all subsets of biomarkers for estimating BAs and assessed their association with mortality to determine the most predictive subset and BA.Clinical biomarkers, including those from physical examinations and blood assays, were assessed in the China Health and Nutrition Survey (CHNS) 2009 wave. Those correlated with chronological age (CA) were combined to produce complete subsets, and BA was estimated by KDM from each subset of biomarkers. A Cox proportional hazards regression model was used to examine and compare each BA's effect size and predictive capacity for all-cause mortality. Validation analysis was performed in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and National Health and Nutrition Examination Survey (NHANES). KD-BA and Levine's BA were compared in all cohorts.A total of 130 918 panels of BAs were estimated from complete subsets comprising 3-17 biomarkers, whose Pearson coefficients with CA varied from 0.39 to 1. The most predictive subset consisted of 5 biomarkers, whose estimated KD-BA had the most predictive accuracy for all-cause mortality. Compared with Levine's BA, the accuracy of the best-fitting KD-BA in predicting death varied among specific populations.All-subset analysis could effectively reduce the number of redundant biomarkers and significantly improve the accuracy of KD-BA in predicting all-cause mortality.