Biological aging increases risk of postoperative morbidity and mortality: an international, multi-cohort study

Biological age often diverges from chronological age, yet its independent impact on surgical outcomes remains poorly defined. We evaluated PhenoAge, a validated biological age metric, in an international multi-cohort study comprising over 430,000 surgical patients across the UK, USA, and South Korea. In the UK Biobank (N = 291,845), PhenoAge was a robust, independent predictor of 1-year mortality (OR 1.043; p < 0.001), major adverse cardiovascular events (OR 1.041; p < 0.001), and 30-day readmission (OR 1.02; p < 0.001), even after adjusting for chronological age, Fried Frailty Index, Charlson comorbidity score, American Society of Anesthesiologists (ASA) physical status, surgical complexity, and other common surgical risk factors. "Fast Agers" faced a 49% higher risk of mortality than "Normal Agers". The main findings were replicated across three independent international cohorts (MOVER OR 1.03; Weill Cornell OR 1.036; INSPIRE OR: 1.05; all p < 0.001), and validated prospectively at a large academic medical center, where PhenoAge predicted acute 3-day complications (OR 1.20; p = 0.015). As a scalable tool leveraging routine laboratory data, PhenoAge facilitates precision gerisurgery by identifying high-risk individuals for prehabilitation and biologically resilient candidates for complex procedures regardless of chronological age.