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·kg 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 ( = 0.009), p70S6K ( = 0.031), p4E-BP1 ( = 0.047), and MPS ( = 0.041) with a greater response to CPH-fed serum, and interaction effects (age × protein) between young and old serum for pmTOR ( = 0.009) and p70S6K ( = 0.016). In addition, significant changes in myotube diameter ( = 0.049), atrogin-1 ( = 0.004), and MuRF-1 ( = 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. 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.