Biological age acceleration, longitudinal change and mortality risk in the Dutch Lifelines cohort

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.