Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs

Abstract

The neonatal period is characterized by rapid growth driven by high rates of skeletal muscle protein synthesis. This high rate of protein synthesis declines with development. In this study, overnight fasted, 7 and 26 d. old pigs either remained fasting or were refed and the activation of growth factor- and nutrient-induced signaling components that regulate translation initiation were measured in skeletal muscle. Activation of the inhibitors of protein synthesis (PTEN, PP2A, and TSC2) increased with age (P<0.05). Neither the abundance nor the activation of AMPK, a potent inhibitor of protein synthesis, changed with age. Activation of positive regulators of protein synthesis (mTOR, S6K1 and 4EBP-1) decreased with age (P<0.05). Furthermore, raptor abundance and raptor-mTOR complex abundance were higher in 7- than in 26 d. old pigs (P<0.05), consistent with higher mTOR activation in younger pigs. The results suggest that the feeding-induced activation of growth factor and nutrient signaling components leading to mRNA translation initiation change with age and this likely contributes to the developmental decline in muscle protein synthesis. (NIH AR44474 and USDA 58-6250-001).