Pace of Aging and Risk of Mortality and Disease: Whitehall II Study Findings

Abstract Background Aging is a major risk factor for morbidity and mortality, but chronological age doesn't fully reflect the heterogeneity in the aging process. The Pace of Aging Index (PoA) quantifies physiological decline using different variables to estimate biological aging. This study aims to develop a PoA from the Whitehall II Study and examine its association with mortality and morbidity. Methods We analyzed 6254 Whitehall II participants. PoA was derived from repeated biomarker measures (systolic blood pressure, LDL, HDL, CRP, fasting glucose, fat mass, heart rate variability, functioning timed walking) collected between Phase 1 and Phase 9. Cox proportional hazards models assessed the association of PoA with mortality, cardiovascular diseases (CVD), dementia, and cancer. The observation period started at Phase 9 (2007-2009) and ended in 2019 for all-cause mortality, incident CVD, and dementia, and 2016 for cancers. Predictive performance of incident CVD was compared with the Framingham Risk Score using C-statistics, Brier scores, and predictive/observed ratios. Results PoA was higher in men vs. women (p < 0.001), non-whites vs. whites (p < 0.001), and individuals with vs. without long-standing illness (p < 0.001), but similar across different occupational grades (p = 0.100). Each unit of increase in standard deviation of PoA was linked to higher mortality (men: RR = 1.61, 95%CI=1.09-2.40; women: RR = 1.22, 95%CI=1.02-1.46), CVD (men: RR = 1.39,95% CI = 1.01-1.90; women: RR = 1.43, 95%CI=1.23-1.66), dementia (men: RR = 2.10, 95%CI=1.16-3.80; women: RR = 1.31, 95%CI=1.05-1.64), and cancer (women: RR = 1.19, 95%CI=1.01-1.40) in the next 10 years. The predictive performance of incident CVD was overall similar to that of the Framingham Risk Score. Conclusions The PoA predicts mortality and chronic disease risk. Integrating biological aging measures into clinical assessments may enhance prevention and early interventions. Further research should validate findings in diverse populations. Key messages • The Pace of Aging Index predicts mortality, cardiovascular diseases, dementia, and cancer, supporting its role as a biological aging biomarker. • Integrating Pace of Aging into clinical assessments may improve early detection and prevention strategies.