Alterations in human muscle protein metabolism with aging: Protein and exercise as countermeasures to offset sarcopenia

Aging is associated with a reduction in skeletal muscle mass-sarcopenia-the etiology of which is multifactorial. One mechanism is that aging has, as one of its hallmarks, a reduced sensitivity of skeletal muscle to the normally potent anabolic effects of protein feeding and resistance exercise, and to the anticatabolic effects of insulin, the combination of which has been termed "anabolic resistance." However, this reduced sensitivity of skeletal muscle to anabolic stimuli may, in some cases, be overcome by providing a greater quantity of the nutrition and/or exercise stimulus. Daily habitual physical activity appears to be a primary determinant of anabolic resistance as we have recently shown that as little as 14 days of reduced ambulatory activity was sufficient to induce anabolic resistance in the elderly by attenuating the postprandial increase in muscle protein synthesis (MPS). The etiology of anabolic resistance is complex and may include alterations in amino acid uptake/utilization, cell signaling status, muscle blood flow, and microvascular perfusion (impacting amino acid delivery and availability). Further, there appears to be sexual dimorphism with advancing age in the response of MPS to amino acid/insulin provision. Maintenance of physical activity during aging is of fundamental importance for skeletal muscle to allow it to appropriately respond to the anabolic effects of nutrition.