Exercise-Induced Epigenetic Regulation of Chchd10 Promoter Methylation Improves Muscle Morphology in Zebrafish

Skeletal muscle activity, such as exercise, enhances mitochondrial function, a process critical for ATP production through oxidative phosphorylation. Mitochondrial dysfunction, often linked to mutations in the chchd10 gene, contributes to the pathogenesis of neurodegenerative and neuromuscular diseases. Although exercise is known to improve mitochondrial performance, its regulatory influence on chchd10 remains poorly defined. In this study, zebrafish (Danio rerio) at three different ages (4, 9, and 15 months) were divided into control and exercise groups, with the latter subjected to a swimming intervention. We observed that exercised male zebrafish exhibited improved muscle morphology across all age groups, marked by increased muscle fiber cross-sectional area and reduced inter-fiber spacing. Transcriptome sequencing via RNA-seq further identified chchd10 as a differentially expressed gene in three age group comparisons. Exercise may be associated with downward regulation of expression of chchd10, which was correlated with increased methylation levels in its promoter region. These results illuminate the epigenetic mechanisms induced by exercise, revealing a novel pathway through which physical activity, potentially via modulation of chchd10, promotes muscle and mitochondrial health.