Abstract
Sarcopenia is the general muscle mass and strength loss associated with ageing. Muscle atrophy could be made worse by exposure to acute periods of immobilization, because muscle disuse by itself is a stimulus for atrophy. Using a model of unilateral hindlimb casting in old adult rats, we have already demonstrated that the primary effect of immobilization was atrophy in the casted leg, but was also surprisingly associated with a retarded atrophy in the non-casted leg during rehabilitation. In search of mechanisms involved in this generalized atrophy, we demonstrated in the present study that contrary to pair-fed non-immobilized control animals, muscle protein synthesis in the non-immobilized limb was unable to adapt and to respond positively to food intake. Because pair-fed control rats did not lose muscle mass, this defect in muscle protein synthesis may represent one of the explanation for the muscle mass loss observed in the non-immobilized rats. Nevertheless, in order to stimulate protein turn over and generate a positive nitrogen balance required to maintain the whole muscle mass in immobilized rats, we tested a dietary free leucine supplementation (an amino acid known for its stimulatory effect on protein metabolism) during the rehabilitation period. Leucine supplementation was able to overcome the anabolic resistance in the non-immobilized limb. A greater muscle protein synthesis up-regulation associated with a stimulation of the mTOR signalling pathway was indeed recorded but it remained inefficient to prevent the loss of muscle in the non-immobilized limb. By contrast, we demonstrated here that whey protein or high protein diets were able to prevent the muscle mass loss of the non-immobilized limb by sustaining muscle protein synthesis during the entire rehabilitation period.
Highlights
Sarcopenia is an age-related loss in skeletal muscle mass and strength associated with normal ageing [1]
In this study, unilateral hindlimb casting in old adult rats induced a muscle mass loss of the controlateral nonimmobilized leg 20 days after cast removal when animals were fed a standard protein diet (i.e. 13% casein as protein source) [5]
Even though we may not had enough data and despite the fact that experiment was not designed to answer this question, we may hypothesize that old adult rats can still adapt to moderate food deprivation and can partially restore a post-prandial stimulation of muscle protein synthesis when the dietary supply in amino acids decreases
Summary
Sarcopenia is an age-related loss in skeletal muscle mass and strength associated with normal ageing [1]. Besides a slow and progressive loss over years, English & Paddon-Jones have suggested that, when ageing, sarcopenia could result from muscle atrophy episodes followed by uncompleted muscle recovery [2]. The authors named this phenomenon the ‘catabolic crisis model’ which has been observed previously after generalized catabolic states including food deprivation [3] or glucocorticoids treatment [4]. We showed for the first time that atrophy occurred in the non-immobilized leg during the rehabilitation period and reached a non-negligible level of 10– 15% decrease after the cast removal [5]. Considering that this general atrophy occurred later during the rehabilitation period
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