Accelerated biological aging has been associated with mortality, but it remains unclear whether longitudinal changes in age acceleration predict long-term mortality risk. In the population-based Dutch Lifelines cohort, we estimated biological age using the Klemera-Doubal method (KDM-BA) and derived KDM-BA acceleration at baseline and follow-up. We examined baseline acceleration (continuous and categorical: < - 1, - 1 to 1 [reference], > 1 year), annual change in acceleration and four aging trajectory groups. Associations with all-cause mortality were assessed using Cox models adjusted for age, sex, socioeconomic status and lifestyle factors. Among 90,632 participants (3,976 deaths; median follow-up 13.8 years), higher baseline KDM-BA acceleration was associated with higher mortality (HR per 1-year increase = 1.07; 95% CI: 1.06-1.08); acceleration > 1 year predicted higher mortality risk (HR = 1.31; 95% CI: 1.21-1.42) compared with - 1 to 1 years. Among 25,752 participants with repeated assessments (879 deaths; median baseline-to-follow-up 4.3 years), a greater annual increase in acceleration was associated with higher mortality (HR per 1-year/year increase = 1.21; 95% CI: 1.07-1.37), and persistent accelerated aging showed the highest risk (HR = 1.39; 95% CI: 1.19-1.62) compared with stable non-accelerated aging. Higher baseline KDM-BA acceleration and worsening acceleration over time were associated with higher long-term all-cause mortality, supporting repeated clinical assessment to monitor biological aging in population settings.
