A novel clinical biomarker-based Physiology Healthy Aging Index and risk of all-cause and cause-specific mortality: A 20-year prospective cohort study

Population aging is accelerating worldwide, with 16% projected to be aged ≥ 65 years by 2050. A practical index reflecting overall aging status is needed for population-based research, as existing indices often require specialised or cognitive assessments. We developed a Physiological Healthy Aging Index (PHAI) using accessible biomarkers and evaluated its association with mortality in Korean adults. A total of 6398 participants aged ≥ 40 years from the Korean Genome and Epidemiology Study (KoGES) Ansan-Ansung cohort followed up for an average duration of 16.5 years (2001-2022). The PHAI, based on systolic blood pressure, fasting blood glucose, serum creatinine, forced vital capacity, and C-reactive protein levels, was scored 0-10, with higher scores indicating healthier aging. Mortality risks across quartiles were estimated using Cox proportional hazard models. Long-term changes were classified as accelerated (decreased scores), stable (unchanged scores), or resilient (increased scores). During 105,597 person-years, 934 deaths occurred (778 age-related, 353 cancer-related, and 184 cardiovascular-related). Higher PHAI quartiles were linked with significantly lower mortality risk versus Q1. Fully adjusted hazard ratios (95% CIs) for all-cause mortality were 0.82 (0.69-0.98) for Q2, 0.50 (0.42-0.60) for Q3, and 0.51 (0.41-0.63) for Q4 (P for trend < 0.001). Similar associations were observed for age-related mortality (HR 0.51, 95% CI 0.40-0.64 for Q4 vs. Q1), cancer (HR 0.66, 95% CI 0.48-0.92), and cardiovascular mortality (HR 0.24, 95% CI 0.13-0.44). Resilient agers had much lower all-cause mortality than accelerated agers (HR 0.21, 95% CI 0.16-0.28), with stable agers also at reduced risk (HR 0.65, 95% CI 0.54-0.77). Higher scores also correlated with a lower cognitive impairment risk. The PHAI is a simple, robust predictor of mortality outcomes, supporting its use as a practical tool for assessing physiological aging in public health and clinical settings.