Consistent with these predictions, rGDF11 treatment activated SMAD3 phosphorylation and induced a dose-dependent upregulation of Atrogin-1 and MuRF1 at both the protein and mRNA levels in C2C12 myotubes, supporting activation of a pro-atrophic ubiquitin-proteasome program.<h4>Conclusion</h4>Circulating GDF11 is elevated in individuals with sarcopenia and appears to partially mediate the protective effects of physical activity. This evidence concerns the gene SMAD3 and sarcopenia.