Multi-Tissue DNA Methylation Remodeling at Mitochondrial Quality Control Genes According to Diet in Rat Aging Models

An adequate mitochondrial quality control system ensures the maintenance of a healthy mitochondrial pool so as to slow down the progressive accumulation of damage affecting mitochondrial function during aging and diseases. The amount and quality of nutrients availability were demonstrated to induce a process of bioenergetics adaptation by influencing the above system via epigenetic modifications. Here, we analyzed DNA samples from differently-aged rats fed a standard or low-calorie diet to evaluate tissue-specific changes in DNA methylation of CpG sites falling within Polg, Polg2, Tfam, Fis1, and Opa1 genes. We found significant changes according to age and tissue type and the administration of the low-calorie diet is responsible for a prevalent increase in DNA methylation levels. Particularly, this increase was more appreciable when this diet was administered during adulthood and at old age. Regression analysis demonstrated that DNA methylation patterns of the analyzed genes were negatively correlated with their expression levels. Data we obtained provide the first evidence about changes in DNA methylation patterns of genes involved in the mitochondrial biogenesis in response to specific diets and demonstrated that epigenetic modifications are involved in the modulation of mitochondrial dynamics driven by age and nutrition.