Vitamin C-Dependent Intergenerational Inheritance of Enhanced Endurance Performance Following Maternal Exercise

Abstract This study addresses an intriguing question of whether maternal exercise can enhance offspring’s physical fitness level. Our findings provide compelling evidence that maternal exercise positively impacts offspring's endurance performance by modulating myofiber composition and promoting mitochondrial biogenesis. Notably, these benefits exhibit intergenerational persistence. Maternal exercise influences DNA methylation level in offspring’s skeletal muscle, exemplified by the demethylation of the Slc23a2 gene - a key component in vitamin C transport - in the F1 and F2 generations. Notably, the beneficial effect of maternal exercise on offspring's endurance performance was absent in global Gulo (a critical enzyme for endogenous vitamin C synthesis) knock-out mice, whereas these transgenerational effects could be replicated through exogenous vitamin C supplementation during gestation. Moreover, vitamin C supplementation stimulated the differentiation of both murine and human myogenic precursor cells into slow muscle fibers, alongside enhanced mitochondrial biogenesis, potentially via TET-mediated DNA demethylation.