Structural and functional modifications occur in skeletal muscle during aging. These defects lead to impairment in muscle strength, contractile capacity and performance. Among factors implicated in this age-related loss of muscle mass, a dysregulation of protein synthesis and breakdown has frequently been reported. Insulin plays a major role in regulating muscle protein metabolism, since its action contributes to increase net gain of muscle protein in animal and humans. More recently, specific actions of insulin on various muscle proteins, notably mitochondrial proteins, have been demonstrated, suggesting that insulin is also a major regulating factor of mitochondrial oxidative phosphorylation in human skeletal muscle. Insulin resistance develops with aging, classically involving changes in glucose tolerance. However, the effect of insulin on protein metabolism is less well documented, and insulin resistance could be involved in age-related muscle protein loss, progressively leading to sarcopenia. Therefore in a more general concept, insulin resistance found in many clinical settings, could be considered as a contributor to muscle wasting.