Cohort study associates longitudinal change in biological age acceleration with all-cause mortality risk

A longitudinal study of the Dutch Lifelines cohort demonstrates that both baseline biological age acceleration and its annual rate of change, measured via clinical biomarkers, are robust predictors of all-cause mortality.

In a study published in GeroScience, researchers evaluated 90,632 baseline participants from the population-based Dutch Lifelines cohort to estimate biological age using the Klemera-Doubal method (KDM-BA).

During a median follow-up of 13.8 years, 3,976 deaths were documented. Higher baseline KDM-BA acceleration was significantly associated with higher mortality risk, with each 1-year increase corresponding to a 7% higher risk of death (HR = 1.07; 95% CI: 1.06–1.08), and baseline acceleration exceeding 1 year predicting a 31% higher risk (HR = 1.31; 95% CI: 1.21–1.42).

Among 25,752 participants with repeated assessments over a median interval of 4.3 years (resulting in 879 subsequent deaths), a greater annual increase in KDM-BA acceleration was associated with elevated mortality risk (HR per 1-year/year increase = 1.21; 95% CI: 1.07–1.37).

Furthermore, individuals showing persistent accelerated aging across both assessments exhibited the highest overall risk of all-cause mortality (HR = 1.39; 95% CI: 1.19–1.62) compared to those with stable, non-accelerated aging.

Most prior validation of biological age acceleration has relied on single-timepoint cross-sectional baseline data. This study is among the first to trace the longitudinal rates of change in a large cohort, showing that temporal changes in age acceleration hold independent prognostic value.

Because KDM-BA is constructed from routinely collected clinical markers (incorporating creatinine, glucose, HbA1c, cholesterol, FEV1, blood pressure, BMI, and waist-to-hip ratio) rather than expensive high-dimensional omics data, it presents a highly scalable, low-cost framework for clinical and population-level longitudinal monitoring.

The clinical validation of longitudinal physiological biomarker tracking supports the market case for continuous diagnostic monitoring and personalized preventative interventions.

The utility of clinical-biomarker cohorts to map systemic physiological decline over long-term clinical horizons strengthens the foundational approach of longevity companies leveraging cohort databases to identify drug targets.

Whether forthcoming clinical trials targeting metabolic, cellular, or systemic aging pathways will evaluate KDM-BA or similar clinical-biomarker biological age models as secondary endpoints to demonstrate a reduction in the rate of biological aging.