title: Dietary protein decreases exercise endurance through rapamycin-sensitive suppression of muscle mitochondria.
abstract: 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 high-protein 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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan; and.
authors.forename: Masanori
authors.initials: M
authors.lastname: Mitsuishi
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Miyashita
authors.forename: Ayako
authors.initials: A
authors.lastname: Muraki
authors.forename: Masanori
authors.initials: M
authors.lastname: Tamaki
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D002460:Cell Line; D004044:Dietary Proteins / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D004044:Dietary Proteins; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: AMPK; TORC1; exercise endurance; muscle mitochondria; physical performance; rapamycin; skeletal muscle mass