Associations between methylation age and brain age in late adolescence

Recent research suggests that biological age, based on DNA methylation or neuroimaging measures, may predict health traits in adulthood more accurately than chronological age. However, whether these findings apply to earlier stages in life is unknown. We therefore aimed to characterise the performance of and interdependence between measures of biological age during adolescence, leveraging longitudinal data from a subsample of young adolescents from the population-based ALSPAC cohort (n=386). We derived four methylation age measures in late adolescence (17-19 years) and a measure of brain age derived from structural neuroimaging data (18-24 years). We then examined associations between these measures of biological age, and their relationship with five measures of physical, cognitive and mental health (8-18 years). Brain age was largely independent of different measures of methylation age, after accounting for age, cell type composition, array and study (beta range: -0.60 to 0.60, all p>0.05). Smoking and BMI were associated with three measures of advanced methylation age (beta range: -0.35 to 0.52, all p<0.05), but not brain age. Depressive symptoms and cognitive ability were unrelated to all measures of biological age. Our findings emphasize the variability of and independence between these methylation- and brain-based measures of age in adolescents. They also highlight the importance of tracking the mosaic of ageing in younger populations.