BioProject

The development of current biological markers of aging has primarily focused on adult samples. More...

The development of current biological markers of aging has primarily focused on adult samples. The epigenetic clock is one promising tool for measuring biological age that shows impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several agerelated phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this crucial gap, we aimed to develop a highly accurate, noninvasive biological measure age specific to pediatric samples by using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032) and the performance was assessed in a separate dataset (n = 689). The DNAm at 94 CpG sites was highly predictive of age in the test cohorts (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease. The BIBO (Dutch abbreviation for Basale Invloeden op Baby Ontwikkleing) is one of the cohorts to develop the PedBE clock. Overall design: In the BIBO cohort (dataset 8), 193 mothers and their children have been followed since week 37 of pregnancy. At age 6 DNA was collected with buccal swabs in 148 of the children, which was used to measure DNA methylation with the Illumina EPIC array by the Kobor Lab at UBC in collaboration with Kieran O'Donnell and Michael Meaney at McGill. Less...