Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods.
One of the most important effects of aging is sarcopenia, which is associated with impaired locomotion and general weakness. In addition, there is increased susceptibility to illness in aging, which often results in muscle wasting episodes. In such instances, the mobilization of muscle proteins provides free amino acids that are used for energetic purpose, the synthesis of acute phase proteins, and the immune response. However, since muscle protein mass is already depleted, the ability of the aged organism to recover from stress is impaired. Therefore, elucidating the mechanisms that result in sarcopenia is of obvious importance. Age-related changes in protein synthesis and proteolysis are rather small and our current methodology does not enable one to establish unequivocally whether sarcopenia results from depressed protein synthesis, increased proteolysis or both. By contrast, in anabolic and catabolic periods, a number of dysregulations in muscle protein turnover became clearly apparent. The aim of this review is to provide an overview of such altered responses to nutrients and catabolic treatments, which may ultimately contribute to explain sarcopenia. This includes impaired recovery in catabolic states, impaired anabolic effects of nutrients, in particular leucine, and a lack of regulation of the ubiquitin-proteasome proteolytic system. These alterations are discussed with respect to modifications in the insulin/IGF-1 axis and glucocorticoid related effects.
Attaix
Didier
D
Human Nutrition Research Center of Clermont-Ferrand, Institut National de la Recherche Agronomique, Nutrition and Protein Metabolism Unit, 63122 Ceyrat, France. attaix@clermont.inra.fr
Mosoni
Laurent
L
Dardevet
Dominique
D
Combaret
Lydie
L
Mirand
Philippe Patureau
PP
Grizard
Jean
J
D000375:Aging / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D013217:Starvation
D000596:Amino Acids; D005938:Glucocorticoids; D007328:Insulin; D009124:Muscle Proteins; D007334:Insulin-Like Growth Factor I