Comparative response of casein protein hydrolysate-fed young and older human serum on in vitro muscle protein metabolism and myotube size

In this study, we used an ex vivo-in vitro model to assess the effect of feeding older (50-70 yr) adults a casein protein hydrolysate (CPH) compared with nonbioactive nonessential amino acid (NEAA) supplement on muscle protein synthesis (MPS) and markers of muscle protein breakdown (MPB). As a secondary objective, to assess any attenuation with aging, we compared the anabolic response to CPH-fed serum from older and young adults. Serum from seven healthy older and seven young men following overnight fast and 60-min postprandial ingestion of CPH or NEAA (0.33 g<middle dot>kg(-1) body mass) was used to condition C2C12 myotube media. Analysis by two-way ANOVA of the fed relative to fasted MPS response revealed a main effect for protein type in pmTOR (P = 0.009), p70S6K (P = 0.031), p4E-BP1 (P = 0.047), and MPS (P = 0.041) with a greater response to CPH-fed serum, and interaction effects (age x protein) between young and old serum for pmTOR (P = 0.009) and p70S6K (P = 0.016). In addition, significant changes in myotube diameter (P = 0.049), atrogin-1 (P = 0.004), and MuRF-1 (P = 0.012) in response to CPH-fed compared with fasted serum were observed with no differences between young and old serum. In conclusion, this study demonstrated that CPH-fed serum from both young and older (50-70 yr) adults can stimulate MPS and muscle growth and can suppress biomarkers of muscle protein breakdown processes. NEW & NOTEWORTHY This study extended previously developed coculture models and found that treating skeletal muscle cells with ex vivo human serum following feeding with a casein protein hydrolysate resulted in greater protein signaling, muscle protein synthesis, muscle growth, and lower expression of genes related to muscle protein breakdown compared with feeding with a nonessential amino acid control. These findings were similar using serum from young and older adults.