Dietary protein decreases exercise endurance through rapamycin-sensitive suppression of muscle mitochondria

Abstract

Mitsuishi M, Miyashita K, Muraki A, Tamaki M, Tanaka K, Itoh H. Dietary protein decreases exercise endurance through rapamycin-sensitive suppression of muscle mitochondria. Am J Physiol Endocrinol Metab 305: E776 -E784, 2013. First published July 23, 2013; doi:10.1152/ajpendo.00145.2013.-Loss of physical performance is linked not only to decreased activity in daily life but also to increased onset of cardiovascular diseases and mortality. A highprotein diet is recommended for aged individuals in order to preserve muscle mass; however, the regulation of muscle mitochondria by dietary protein has not been clarified. We investigated the long-term effects of a high-protein diet on muscle properties, focusing especially on muscle mitochondria. Mice were fed a high-protein diet from the age of 8 wk and examined for mitochondrial properties and exercise endurance at the ages of 20 and 50 wk. Compared with normal chow, a high-protein diet significantly decreased the amount of muscle mitochondria, mitochondrial activity, and running distance at 50 wk, although it increased muscle mass and grip power. Inhibition of TORC1-dependent signal pathways by rapamycin from 8 wk suppressed the decline in mitochondria and exercise endurance observed when mice were fed the high-protein diet in association with preserved AMPK activity. Collectively, these findings suggest a role for dietary protein as a suppressor of muscle mitochondria and indicate that the age-associated decline in exercise endurance might be accelerated by excessive dietary protein through rapamycin-sensitive suppression of muscle mitochondria. skeletal muscle mass; muscle mitochondria; physical performance; exercise endurance; TORC1; AMPK; rapamycin MAINTENANCE OF PHYSICAL PERFORMANCE is essential for a healthy life, especially among the elderly. The loss of muscle mass associated with aging, termed sarcopenia, is known to predict a wide range of diseases and morbidity. Sarcopenic individuals suffer from increased risk of falls and fractures and, as a result, a 1.5 to 4.6-fold higher risk of loss of independence compared with those with a normal volume of muscle mass (19,35). Moreover, inactive individuals are at higher risk of coronary heart diseases and all-cause mortality (4,5,7,22,33,38), and the relative risk for coronary heart diseases is reported to be similar between inactivity and smoking, hypertension, or dyslipidemia (16).The age-associated change in muscle is not limited to a decrease in muscle volume; the amount of muscle mitochondria decreases with aging (30, 37). Because skeletal muscle consumes 40% of total energy intake and plays a vital role in whole body energy homeostasis (12, 47), the age-associated reduction in mitochondrial amount and function in skeletal muscle is likely to contribute to an age-associated decline in physical activity, and the development of obesity and diabetes in the elderly, through dysregulation of energy homeostasis (31, 32, 34). Unlike obesity or osteoporosis, however, muscle aging is not recognized as a pathological ...

Effect of dietary protein content shift on aging in elderly rats by comprehensive quantitative score and metabolomics analysis

“…In a study by Mitchell et al, protein restriction was found to improve levels of oxidative stress and inflammation in mice (46). In the study by Mitsuishi et al, weight and exercise capacity were increased in older adults by a HP dietary intervention (47). These results are consistent with the findings in our study.…”

Applications of Medium-Chain Triglycerides in Foods

“…In addition, a balanced intake of energy and protein is important when addressing malnutrition in the elderly. Recent studies have shown that high protein intake can increase skeletal muscle mass and muscle strength, but can also cause functional decline in endurance, mitochondrial function, and glucose tolerance ( 77 ). In order to prevent and address malnutrition, sarcopenia, and frailty, it may be useful to include MCTs, which are easily utilized as energy, along with an appropriate amount of protein intake, considering the specific physiological conditions of the elderly.…”

Dietary restriction, mitochondrial function and aging: from yeast to humans

“…In mammals, rapamycin is a potent inhibitor of TORC1, and also of TORC2 at high doses or chronic treatments [132]. Rapamycin treatment drastically attenuates the detrimental effects of both high protein and high fat diets in mice [133]. Specifically, in mice a significant decrease in the amount and function of muscle mitochondria was seen following a life-long high-protein diet, which was reverted by chronic treatment with rapamycin [133].…”

“…Rapamycin treatment drastically attenuates the detrimental effects of both high protein and high fat diets in mice [133]. Specifically, in mice a significant decrease in the amount and function of muscle mitochondria was seen following a life-long high-protein diet, which was reverted by chronic treatment with rapamycin [133]. Inhibition of mTOR by rapamycin also activates selective degradation of unfit mitochondria through mitophagy, a process critical for mitochondrial quality control.…”