Synergistic effects of caloric restriction together with protein intake on skeletal muscle metabolism in middle‐aged rats

Abstract

Rationale Caloric restriction (CR) reverses some age-related alterations in muscle mitochondrial function. However, CR does not prevent the decline in ATP production necessary to sustain muscle protein synthesis rate (FSR) and contraction. We hypothesized that a limited ATP production is linked to a reduction in mitochondrial protein turnover, which could be counteracted by increasing amino acid availability during CR. Methods Wistar rats (16 mo, n=30) were fed either ad libitum (AL), 40% protein-energy restricted (PER) or 40% energy restricted (ER) for 5 months. Muscle mass and strength (grip force) were measured. Mitochondrial coupling, ATP production, and FSR (using 13C-valine as a tracer) were determined in tibialis anterior (TA) and soleus (SO) muscles mitochondria. Myosin and actin FSR were also investigated. Results ER diet improved mitochondrial ATP production and coupling in TA (p<0.05 vs AL) and in SO muscles (p=0.07). TA mitochondrial FSR was also enhanced by ER diet while PER decreased it (p<0.05 vs AL). ER diet was able to maintain TA mass and to improve myosin and actin FSR (p<0.05 vs PER and AL) and muscle strength (p<0.05 vs AL). Protein synthesis rates were not affected by the diets in SO muscle. Conclusions Deprivation of energy with maintenance of protein intake initiated in late middle age improves mitochondrial function, ATP production and protein turnover in skeletal muscles. The present study supports the hypothesis that sarcopenia is nutritionally preventable by using strategies associating limiting energy intake but favouring sufficient protein intake of various quality in the diet.