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Atrophie et récupération musculaire chez le rat âgé immobilisé : rôle de la nutrition

Abstract : Sarcopenia, the age-related muscle mass loss, might be partially explained by an impairedmuscle mass recovery of skeletal muscle mass after a catabolic state. Thus, immobilization periodswhich increase with aging could induce a muscle atrophy followed by a lack of muscle massrecovery. An imbalance of protein and cellular metabolisms are certainly involved in this absenceof recovery. The aim on this Ph.D thesis was to explore the mechanisms involved in muscle massatrophy during immobilization and their possible alteration during the recovery period in old rats.Old rats were immobilized for 8 days by unilateral hind limb casting and then allowed torecover for 40 days. Our results showed that animals fed a 13% casein diet wasted muscle mass inimmobilized muscles but, contrarily to adult animals, they never recovered the muscle mass loss.Muscle atrophy was due to 1/ an increase of apoptotic and ubiquitine-proteasome-dependentproteolytic pathways, 2/ a decrease of muscle regeneration processes and 3/ a decrease of muscleprotein synthesis at the fed state. These changes paralleled an increase of intracellular inflammationand oxidative stress. As these parameters were only normalized during the recovery period, theresultant nitrogen balance was then not enough positive as required for the muscle protein gain,hence contributing to the age-related incomplete muscle mass recovery. We tested free leucinesupplementation (an amino acid known for its stimulatory effect on protein metabolism) during therecovery period to improve muscle mass gain. This supplementation induced a greater muscleprotein synthesis in supplemented animals, but without any muscle mass gain. However, wedemonstrated here for the first time that muscle protein accretion after immobilization-inducedatrophy could be achieved with whey protein or high protein diets.In conclusion, we demonstrated that immobilization in old rats induced a muscle mass atrophyfollowed by an incomplete recovery, hence contributing to the development of sarcopenia. We alsodemonstrated that this lack of recovery cannot be overcome by a dietary free leucinesupplementation, despite a positive effect on protein metabolism, contrarily to high protein andwhey protein diets.
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Submitted on : Friday, July 20, 2012 - 3:07:22 PM
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Hugues Magne. Atrophie et récupération musculaire chez le rat âgé immobilisé : rôle de la nutrition. Médecine humaine et pathologie. Université d'Auvergne - Clermont-Ferrand I, 2011. Français. ⟨NNT : 2011CLF1MM17⟩. ⟨tel-00719700⟩

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