Myostatin gene knockout increases muscle size and usually improves muscle function in several species including humans (Schuelke et al., 2004). Conversely systemic myostatin overexpression causes cachexia in mice (Zimmers et al., 2002). Myostatin activity is additionally dependent on interacting serum proteins such as follistatin, follistatin-related gene (FLRG) and GDF-associated serum protein-1 (GASP1). The aim of this study was to test whether serum concentrations of myostatin and known interacting serum proteins differed between young men and two groups of men over 65 years with mild or severe sarcopenia defined on the basis of reduced knee extensor torque compared with young men (Lauretani et al., 2003). Venous, fasting blood samples were obtained from young men (Y; 22±2 years, n=20), elderly men with mild sarcopenia (S1; 69±3 years; knee extensor torque 1-2 SD below Y, n=20) and elderly men with severe sarcopenia (S2; 76±6 years; torque >2 SD below Y, n=26). Maximum voluntary isometric knee extension torque at 90° was measured using an isokinetic dynamometer and mid-thigh cross sectional area (CSA) using MRI. Myostatin, FLRG, GASP1, follistatin, IGF-1 and free testosterone were measured using immunoassays. Groups were compared using one-way ANOVA. Data are shown as mean±SD. This study was approved by the North of Scotland Research Ethics Committee. Isometric knee extension torque of the dominant leg and quadriceps femoris CSA were significantly higher in Y (266±54 Nm-1; 8686±1154 mm2) than in S1 (183±17 Nm-1; 6621±718 mm2) and S2 (127±23 Nm-1; 5846±591 mm2), respectively. Differences between groups were p≤0.01 for all comparisons. There was a trend (p=0.06) towards a higher FLRG concentration in Y (20±8 ng ml-1) when compared with S1 (15±6 ng ml-1) and S2 (17±8 ng ml-1). Myostatin, follistatin and GASP-1 did not differ significantly between groups. IGF-1 and free testosterone were both significantly lower in the sarcopenic groups compared to Y (p<0.001). This is the first report where both serum myostatin and myostatin-interacting factors have been measured in relation to human sarcopenia. The concentration of myostatin was 46% lower in young men in this study compared with data from Lakshman et al. (2009) probably due to differences in the calibration of the assay. We additionally show that follistatin, FLRG and GASP-1 are not different between groups. This suggests that the serum myostatin system is unaltered in sarcopenia although the FLRG results need to be confirmed given the lower FLRG concentration in sarcopenic men. IGF-1 and free testosterone were lower in sarcopenic men compared with young men confirming earlier reports.