Declining levels of physical activity and fitness in children and youth are linked to negative health outcomes. This study investigates whether maternal exercise can enhance offspring's physical fitness. Our results demonstrate that maternal exercise improves offspring's endurance by changing muscle fiber composition and promoting mitochondrial biogenesis, with benefits lasting across generations. This improvement is associated with changes in DNA methylation, specifically the demethylation of the Slc23a2 gene, which codes for SVCT2, crucial for vitamin C (VC) transport, in F1 and F2 generations. Importantly, VC administration during pregnancy mimics the transgenerational benefits of exercise on offspring fitness, but these benefits are absent in genetic VC deficiency mice. VC supplementation increases TET2 expression in murine and human myogenic cells, regulating DNA methylation, promoting the development of oxidative fibers, and enhancing mitochondrial biogenesis. This study highlights the VC-TET2-SVCT2 pathway as a key mechanism for the transgenerational endurance benefits of maternal exercise, suggesting potential strategies to enhance maternal and child health.
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