Theaflavin Promotes Myogenic Differentiation by Regulating the Cell Cycle and Surface Mechanical Properties of C2C12 Cells

Aging and muscle diseases often lead to a decline in the differentiation capacity of myoblasts, which in turn results in the deterioration of skeletal muscle (SkM) function and impairment of regeneration ability after injury. Theaflavins, the "gold molecules" found in black tea, have been reported to possess various biological activities and have a positive effect on maintaining human health. In this study, we found that among the four theaflavins (theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3′-gallate (TF2B), and theaflavin-3,3′-digallate (TF3) monomers), TF1 (20 μM) significantly promoted the fusion index of myoblasts, number of mature myotubes, and degree of myotube development. By combining transcriptomics, bioinformatics, and molecular biology experiments, we showed that TF1 may promote myoblast differentiation by (1) regulating the withdrawal of myoblasts from the cell cycle, inducing the release of myogenic factors (MyoD, MyoG, and MyHC) and accelerating myogenic differentiation and (2) regulating the adhesion force of myoblasts and mechanical properties of mature myotubes and promoting the migration, fusion, and development of myoblasts. In conclusion, our study outcomes show that TF1 can promote myoblast differentiation and regulate myotube mechanical properties. It is a potential dietary supplement for the elderly. Our findings provide a new scientific basis for the relationship between tea drinking and aging.