Developmental Dynamics of Blood DNA Methylation in Dairy Cattle from Birth to Adulthood: a longitudinal study based on enzymatic methyl-sequencing (EM-seq).

It is also one of the most promising biomarkers for biological age prediction, particularly through the development of epigenetic clocks. In this study, we analyzed DNA methylation dynamics in Holstein Friesian dairy cattle across three developmental stages: birth, weaning, and adulthood, using enzymatic methyl-sequencing (EM-seq) data obtained from longitudinal blood samples collected from six female individuals.

The results revealed variable methylation profiles across developmental stages, particularly in promoter regions. Differential methylation analysis highlighted marked epigenetic remodeling between birth and weaning (662,571 differentially methylated CpG sites, DMCs), as well as between weaning and adulthood (190,437 DMCs), with a global trend toward hypomethylation in adulthood. Furthermore, estimation of blood cell proportions by deconvolution indicated that methylation variations were partly associated with changes in cellular composition during development, suggesting that age alone did not fully explain the observed variability.