Abstract Growth differentiation factor 11 (GDF11) and Myostatin (GDF8) are circulating factor shown to reduce cardiac hypertrophy of aged animals. Although GDF11 and GDF8 have high structural homology, it seems that GDF11 is had a more potent effect on reducing cardiomyocytes size, albeit GDF11 quantification methods have been recently questioned. In this study, we developed the IP based-PRM- LC-MS/MS method for measuring the GDF8 and GDF11 in one assay. The method demonstrated discriminatory power and allow the quantification of both proteins. Comparison of young and old group of mice show declination of both, GDF8 and GDF11 during aging.