ABSTRACT: Physical exercise has been shown to induce epigenetic modifications with various health implications, and directly affect DNA methylation. The objectives of the present work were: 1) to identify differently methylated genes (DMGs) in saliva of school-aged children following a 3-month integrated neuromuscular training (INT); and 2) to explore if any of these genes are considered core-genes, i.e., genes of essential importance within the human genome. An additional goal was to locate the methylation changes in those genes in relation to the transcription start site (TSS) and the CpG site. Forty children (17 boys and 23 girls) were recruited from schools in Girona, Spain and allocated into control (N=20) or INT (N=20) group. Genome-wide DNA methylation analysis was performed with the Illumina 900K microarray. Core-genes were identified based on their participation in the enriched pathways, high connectivity (≥10) and as target-genes of key-transcription factors, using the bioinformatics software Metascape and Cytoscape, and the ENCODE dataset. There were 1200 DMGs in the control group and 414 DMGs in the INT group (p<0.05). After screening among the DMGs, no core-genes were identified in the control group, but 17 core-genes were identified in the INT group. Remarkably, the 3-month-INT epigenetically modified 17 genes that are of essential importance within the human genome, related to inflammation, fat metabolism, protein metabolism, ATP binding and growth, as well as to metabolic, cardiovascular, neurodegenerative diseases, musculoskeletal disorders, cancer and various syndromes (e.g., Noonan syndrome, Perry syndrome). Moreover, 88% of the methylation changes were close to the TSS, and 59% were in CpG islands. A 3-month-INT induced substantial epigenetic modifications with potential implications for disease prevention and health promotion in school-aged children.
