Epigenetic and brain age across development: Performance and associations in the MIND consortium

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ABSTRACT Understanding how biological age measures perform across development lays the groundwork for investigations into lifespan trajectories of healthy aging. We provide the most comprehensive assessment of epigenetic and brain age models across development (birth to 24 years; ≤20,917 observations across 15 cohorts), evaluating how these models associate with chronological age and with each other, and how these associations change across development. Chronological age-prediction accuracy of epigenetic and brain age models was modest and varied substantially. Accuracy improved with age and stabilized by middle childhood. Few brain and fewer epigenetic clocks performed stably and well across all developmental stages. Performance was better when age range and tissue corresponded between training and testing data. Associations between epigenetic-brain age residuals were small, and changed little across development, tissues or clock generation. Given this developmentally dynamic system of epigenetic-brain age performances and associations, we give key recommendations to improve developmental research in this field.

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