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Synergistic effects of caloric restriction with maintained protein intake on skeletal muscle performance in 21-month-old rats: a mitochondria-mediated pathway

Aude Zangarelli^*,,, Emilie Chanseaume^*,,, Béatrice Morio^*,,, Corinne Brugère^*,,, Laurent Mosoni^*,,, Paulette Rousset^*,,, Christophe Giraudet^*,,, Véronique Patrac^*,,, Pierre Gachon^*,,, Yves Boirie^*,,,|| and Stéphane Walrand^*,,

^* INRA, UMR1019, UNH, Clermont-Ferrand, France;

Université Clemont 1, UFR Médicine,

UMR1019, Clermont-Ferrand, France;

CRNH Auvergne, Clemont-Ferrand, France; and

^|| CHU Clermont-Ferrand, Hôpital Gabriel Montpied, Clemont-Ferrand, France

¹Correspondence: Unité de Nutrition Humaine, UMR Université d’Auvergne/INRA, Centre de Recherche en Nutrition Humaine, CHU de Clermont-Ferrand, Clermont-Ferrand, France. E-mail: boirie{at}sancy.clermont.inra.fr

Caloric restriction (CR) delays the onset of age-related mitochondrial abnormalities but does not prevent the decline in ATP production needed to sustain muscle protein fractional synthesis rate (FSR) and contractile activity. We hypothesized that improving mitochondrial activity and FSR using a CR diet with maintained protein intakes could enhance myofibrillar protein FSR and consequently improve muscle strength in aging rats. Wistar rats (21 months old) were fed either an ad libitum (AL), 40% protein-energy restricted (PER) or 40% AL-isonitrogenous energy restricted (ER) diet for 5 months. ATP production, electron transport chain activity, reactive oxygen species (ROS) generation, protein carbonyl content and FSR were determined in both tibialis anterior (TA) and soleus muscle mitochondria. Myosin and actin FSR and grip force were also investigated. The ER diet led to improved mitochondrial activity and ATP production in the TA and soleus muscles in comparison with PER. Furthermore, mitochondrial FSR in the TA was enhanced under the ER diet but diminished under the PER. Mitochondrial protein carbonyl content was decreased by both the ER and PER diets. The ER diet was able to improve myosin and actin FSR and grip force. Therefore, the synergistic effects of CR with maintained protein intake may help to limit the progression of sarcopenia by optimizing the turnover rates and functions of major proteins in skeletal muscle.—Zangarelli, A., Chanseaume, E., Morio, B., Brugère, C., Mosoni, L., Rousset, P., Giraudet, C., Patrac, V., Gachon, P., Boirie, Y., Walrand, S. Synergistic effects of caloric restriction with maintained protein intake on skeletal muscle performance in 21-month-old rats: a mitochondria-mediated pathway.

Key Words: age • skeletal muscle • mitochondria • caloric restriction • protein intake