Difference between Biological Age and Chronological Age Predicts Mortality and Hospitalization in a Longitudinal Adult Cohort

Biological age (BA) reflects overall health status and may deviate from chronological age (CA). Whether the magnitude of this difference (Agediff) independently predicts hospitalization and mortality remains unknown. Retrospective longitudinal cohort of 2,597 adults (27.5% women), aged 21-92 years, participating in an executive screening program at Sheba Medical Center, Israel, contributing 6,772 clinical encounters between 2006 and 2020, mean follow-up 9.2 (2.2) years. BA was estimated to use a previously established deep-learning model trained on routine clinical laboratory tests. Bayesian time-dependent Cox models evaluated associations between Agediff and all-cause mortality, and negative-binomial models were applied to hospitalizations, adjusting for age, sex, BMI, smoking, and baseline comorbidities. The Agediff associated with a hazard ratio (HR) of 1.5 for mortality was determined for each chronological age, and Agediff ×age interaction was tested. Each 1-year increase in Agediff was associated with a 15% higher mortality hazard (HR 1.15, 95% CI 1.10-1.21) and a 6% higher hospitalization rate (incidence rate ratio 1.06, 95% CI 1.03-1.09). The Agediff ×age interaction was not significant (p = 0.56). The Agediff required to reach HR = 1.5 decreased with chronological age, from approximately 5 years at age 40 to 3 years at age 80. Agediff ≥3 years was associated with a clinically significant increase in mortality. In this cohort, a BA estimated from routine laboratory results exceeding CA by 3 or more years was associated with increased hospitalization and mortality risk, suggesting potential utility for risk stratification in clinical settings.