Cellular and Molecular Mechanisms of Growth Hormone Action on Skeletal Muscle: Implications for Treatment of Age-Associated Sarcopenia

Abstract

The cellular and molecular bases of growth hormone (GH) action on skeletal muscle will be reviewed. Since almost all actions of GH on skeletal muscle occur via locally produced insulin-like growth factor(IGF), this review will focus on the mechanisms of IGF action in skeletal muscle. IGF has profound effects on skeletal muscle precursor cell activities, including stimulation of myoblast proliferation and differentiation, and inhibition of myoblast apoptosis. However, it is unclear whether IGF has any direct actions on skeletal muscle fibers themselves, or contributes to muscle hypertrophy only indirectly through increases in muscle fiber nuclear numbers. Therefore, it is unclear whether IGF can maintain muscle mass without stimulating cell proliferation. The changes that occur in aging skeletal muscle, and the role of declining IGF and IGF receptor expression levels in these changes will also be outlined. There is ample experimental evidence that IGF is essential for normal skeletal muscle growth and regeneration, but the exact role of IGF during muscle aging is still unclear. Various strategies to target age-associated skeletal muscle atrophy and the gaps in basic scientific understanding that need to be filled in order to rationally design such therapies are outlined.