Role of IGF-1 in age-related loss of skeletal muscle mass and function

Abstract

While insulin-like growth factor-1 (IGF-1) is closely involved in the growth, hypertrophy and maintenance of skeletal muscle mass, the role of IGF-1 in age-related muscle wasting (sarcopenia) is unclear: this is the focus of the present discussion. The complexity of the IGF-1 system that involves different IGF-1 isoforms, binding proteins and receptors, with modulation of systemic IGF-1 levels by growth hormone (GH) is first outlined. The classic IGF-1 signalling pathways in skeletal muscle with a focus on the central role of Akt in protein synthesis and degradation are presented and various conditions that can impair IGF-1 signalling are discussed with respect to inflammation (TNF), oxidative stress (ROS) and lipids. Complex interactions between other factors that influence the age-related decrease in IGF-1 activity are addressed, including GH, nutrition, caloric restriction, Klotho and Vitamin D. Finally, the potential for therapeutic interventions for sarcopenia related to IGF-1 signalling is considered. The big questions are 'to what extent does IGF-1 contribute to sarcopenia' and 'can elevated IGF-1 prevent or reverse sarcopenia?