1Blottner, D, Salanova, M, Puttmann, B, et al. (2006) Human skeletal muscle structure and function preserved by vibration muscle exercise following 55 days of bed rest. Eur J Appl Physiol 97, 261–271.
2Kortebein, P, Ferrando, A, Lombeida, J, et al. (2007) Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 297, 1772–1774.
3Pavy-Le, TA, Heer, M, Narici, MV, et al. (2007) From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 101, 143–194.
4English, KL & Paddon-Jones, D (2010) Protecting muscle mass and function in older adults during bed rest. Curr Opin Clin Nutr Metab Care 13, 34–39.
5Gill, TM, Allore, H & Guo, Z (2004) The deleterious effects of bed rest among community-living older persons. J Gerontol A Biol Sci Med Sci 59, 755–761.
6Nair, KS (2005) Aging muscle. Am J Clin Nutr 81, 953–963.
7Short, KR, Vittone, JL, Bigelow, ML, et al. (2005) Changes in myosin heavy chain mRNA and protein expression in human skeletal muscle with age and endurance exercise training. J Appl Physiol 99, 95–102.
8Yarasheski, KE, Pak-Loduca, J, Hasten, DL, et al. (1999) Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men ≥ 76 yr old. Am J Physiol 277, E118–E125.
9Ferrando, AA, Lane, HW, Stuart, CA, et al. (1996) Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol 270, E627–E633.
10Phillips, SM, Glover, EI & Rennie, MJ (2009) Alterations of protein turnover underlying disuse atrophy in human skeletal muscle. J Appl Physiol 107, 645–654.
11Stein, TP, Leskiw, MJ, Schluter, MD, et al. (1999) Protein kinetics during and after long-duration spaceflight on MIR. Am J Physiol 276, E1014–E1021.
12Stevenson, EJ, Giresi, PG, Koncarevic, A, et al. (2003) Global analysis of gene expression patterns during disuse atrophy in rat skeletal muscle. J Physiol 551, 33–48.
13Boonyarom, O & Inui, K (2006) Atrophy and hypertrophy of skeletal muscles: structural and functional aspects. Acta Physiol (Oxf) 188, 77–89.
14Morris, CA, Morris, LD, Kennedy, AR, et al. (2005) Attenuation of skeletal muscle atrophy via protease inhibition. J Appl Physiol 99, 1719–1727.
15Jones, SW, Hill, RJ, Krasney, PA, et al. (2004) Disuse atrophy and exercise rehabilitation in humans profoundly affects the expression of genes associated with the regulation of skeletal muscle mass. FASEB J 18, 1025–1027.
16Tesch, PA, von Walden, F, Gustafsson, T, et al. (2008) Skeletal muscle proteolysis in response to short-term unloading in humans. J Appl Physiol 105, 902–906.
17Glover, EI, Yasuda, N, Tarnopolsky, MA, et al. (2010) Little change in markers of protein breakdown and oxidative stress in humans in immobilization-induced skeletal muscle atrophy. Appl Physiol Nutr Metab 35, 125–133.
18Jaspers, SR & Tischler, ME (1984) Atrophy and growth failure of rat hindlimb muscles in tail-cast suspension. J Appl Physiol 57, 1472–1479.
19Loughna, P, Goldspink, G & Goldspink, DF (1986) Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles. J Appl Physiol 61, 173–179.
20Munoz, KA, Satarug, S & Tischler, ME (1993) Time course of the response of myofibrillar and sarcoplasmic protein metabolism to unweighting of the soleus muscle. Metabolism 42, 1006–1012.
21Zdanowicz, MM & Teichberg, S (2003) Effects of insulin-like growth factor-1/binding protein-3 complex on muscle atrophy in rats. Exp Biol Med (Maywood) 228, 891–897.
22Attaix, D, Ventadour, S, Codran, A, et al. (2005) The ubiquitin–proteasome system and skeletal muscle wasting. Essays Biochem 41, 173–186.
23Cohen, S, Brault, JJ, Gygi, SP, et al. (2009) During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol 185, 1083–1095.
24Polge, C, Heng, AE, Jarzaguet, M, et al. (2011) Muscle actin is polyubiquitinylated in vitro and in vivo and targeted for breakdown by the E3 ligase MuRF1. FASEB J 25, 3790–3802.
25Ikemoto, M, Nikawa, T, Takeda, S, et al. (2001) Space shuttle flight (STS-90) enhances degradation of rat myosin heavy chain in association with activation of ubiquitin–proteasome pathway. FASEB J 15, 1279–1281.
26Taillandier, D, Aurousseau, E, Meynial-Denis, D, et al. (1996) Coordinate activation of lysosomal, Ca 2+-activated and ATP-ubiquitin-dependent proteinases in the unweighted rat soleus muscle. Biochem J 316, 65–72.
27Taillandier, D, Aurousseau, E, Combaret, L, et al. (2003) Regulation of proteolysis during reloading of the unweighted soleus muscle. Int J Biochem Cell Biol 35, 665–675.
28Vazeille, E, Codran, A, Claustre, A, et al. (2008) The ubiquitin–proteasome and the mitochondria-associated apoptotic pathways are sequentially downregulated during recovery after immobilization-induced muscle atrophy. Am J Physiol Endocrinol Metab 295, E1181–E1190.
29Vazeille, E, Slimani, L, Claustre, A, et al. (2012) Curcumin treatment prevents increased proteasome and apoptosome activities in rat skeletal muscle during reloading and improves subsequent recovery. J Nutr Biochem 23, 245–251.
30Magne, H, Savary-Auzeloux, I, Vazeille, E, et al. (2011) Lack of muscle recovery after immobilization in old rats does not result from a defect in normalization of the ubiquitin–proteasome and the caspase-dependent apoptotic pathways. J Physiol 589, 511–524.
31Magne, H, Savary-Auzeloux, I, Migne, C, et al. (2012) Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing. J Physiol 590, 2035–2049.
32Pattison, JS, Folk, LC, Madsen, RW, et al. (2003) Selected contribution: identification of differentially expressed genes between young and old rat soleus muscle during recovery from immobilization-induced atrophy. J Appl Physiol 95, 2171–2179.
33Pattison, JS, Folk, LC, Madsen, RW, et al. (2003) Transcriptional profiling identifies extensive downregulation of extracellular matrix gene expression in sarcopenic rat soleus muscle. Physiol Genomics 15, 34–43.
34Hasselgren, PO & Fischer, JE (2001) Muscle cachexia: current concepts of intracellular mechanisms and molecular regulation. Ann Surg 233, 9–17.
35Huang, J & Forsberg, NE (1998) Role of calpain in skeletal-muscle protein degradation. Proc Natl Acad Sci U S A 95, 12100–12105.
36Goll, DE, Thompson, VF, Li, H, et al. (2003) The calpain system. Physiol Rev 83, 731–801.
37Salazar, JJ, Michele, DE & Brooks, SV (2010) Inhibition of calpain prevents muscle weakness and disruption of sarcomere structure during hindlimb suspension. J Appl Physiol 108, 120–127.
38Liang, XH, Jackson, S, Seaman, M, et al. (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672–676.
39Andrianjafiniony, T, Dupre-Aucouturier, S, Letexier, D, et al. (2010) Oxidative stress, apoptosis, and proteolysis in skeletal muscle repair after unloading. Am J Physiol Cell Physiol 299, C307–C315.
40O'Leary, MF & Hood, DA (2009) Denervation-induced oxidative stress and autophagy signaling in muscle. Autophagy 5, 230–231.
41Zhao, J, Brault, JJ, Schild, A, et al. (2007) FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 6, 472–483.
42Biolo, G, Ciocchi, B, Lebenstedt, M, et al. (2004) Short-term bed rest impairs amino acid-induced protein anabolism in humans. J Physiol 558, 381–388.
43Gibson, JN, Halliday, D, Morrison, WL, et al. (1987) Decrease in human quadriceps muscle protein turnover consequent upon leg immobilization. Clin Sci (Lond) 72, 503–509.
44Lovejoy, JC, Smith, SR, Zachwieja, JJ, et al. (1999) Low-dose T3 improves the bed rest model of simulated weightlessness in men and women. Am J Physiol 277, E370–E379.
45Shangraw, RE, Stuart, CA, Prince, MJ, et al. (1988) Insulin responsiveness of protein metabolism in vivo following bedrest in humans. Am J Physiol 255, E548–E558.
46Stein, TP, Schluter, MD, Leskiw, MJ, et al. (1999) Attenuation of the protein wasting associated with bed rest by branched-chain amino acids. Nutrition 15, 656–660.
47Stuart, CA, Shangraw, RE, Peters, EJ, et al. (1990) Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis. Am J Clin Nutr 52, 509–514.
48de Boer, MD, Selby, A, Atherton, P, et al. (2007) The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse. J Physiol 585, 241–251.
49Glover, EI, Phillips, SM, Oates, BR, et al. (2008) Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion. J Physiol 586, 6049–6061.
50Rennie, MJ, Wackerhage, H, Spangenburg, EE, et al. (2004) Control of the size of the human muscle mass. Annu Rev Physiol 66, 799–828.
51Dardevet, D, Remond, D, Peyron, MA, et al. (2012) Muscle wasting and resistance of muscle anabolism: the ‘anabolic threshold concept’ for adapted nutritional strategies during sarcopenia. ScientificWorldJournal 2012, 269531.
52Bodine, SC, Stitt, TN, Gonzalez, M, et al. (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3, 1014–1019.
53O'Keefe, MP, Perez, FR, Sloniger, JA, et al. (2004) Enhanced insulin action on glucose transport and insulin signaling in 7-day unweighted rat soleus muscle. J Appl Physiol 97, 63–71.
54Sugiura, T, Abe, N, Nagano, M, et al. (2005) Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading. Am J Physiol Regul Integr Comp Physiol 288, R1273–R1278.
55Hunter, RB, Stevenson, E, Koncarevic, A, et al. (2002) Activation of an alternative NF-κB pathway in skeletal muscle during disuse atrophy. FASEB J 16, 529–538.
56Morris, RT, Spangenburg, EE & Booth, FW (2004) Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle. J Appl Physiol 96, 398–404.
57You, JS, Park, MN, Song, W, et al. (2010) Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats. Appl Physiol Nutr Metab 35, 310–318.
58Booth, FW & Kirby, CR (1992) Changes in skeletal muscle gene expression consequent to altered weight bearing. Am J Physiol 262, R329–R332.
59Lagirand-Cantaloube, J, Offner, N, Csibi, A, et al. (2008) The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. EMBO J 27, 1266–1276.
60Sandri, M, Sandri, C, Gilbert, A, et al. (2004) Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117, 399–412.
61Sandri, M (2008) Signaling in muscle atrophy and hypertrophy. Physiology (Bethesda) 23, 160–170.
62Kandarian, SC & Jackman, RW (2006) Intracellular signaling during skeletal muscle atrophy. Muscle Nerve 33, 155–165.
63Romanello, V, Guadagnin, E, Gomes, L, et al. (2010) Mitochondrial fission and remodelling contributes to muscle atrophy. EMBO J 29, 1774–1785.
64Bae, SK, Cha, HN, Ju, TJ, et al. (2012) Deficiency of inducible nitric oxide synthase attenuates immobilization-induced skeletal muscle atrophy in mice. J Appl Physiol 113, 114–123.
65Guttridge, DC (2004) Signaling pathways weigh in on decisions to make or break skeletal muscle. Curr Opin Clin Nutr Metab Care 7, 443–450.
66Leger, B, Cartoni, R, Praz, M, et al. (2006) Akt signalling through GSK-3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 576, 923–933.
67Stitt, TN, Drujan, D, Clarke, BA, et al. (2004) The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 14, 395–403.
68Allen, DL, Yasui, W, Tanaka, T, et al. (1996) Myonuclear number and myosin heavy chain expression in rat soleus single muscle fibers after spaceflight. J Appl Physiol 81, 145–151.
69Leeuwenburgh, C, Gurley, CM, Strotman, BA, et al. (2005) Age-related differences in apoptosis with disuse atrophy in soleus muscle. Am J Physiol Regul Integr Comp Physiol 288, R1288–R1296.
70Smith, HK, Maxwell, L, Martyn, JA, et al. (2000) Nuclear DNA fragmentation and morphological alterations in adult rabbit skeletal muscle after short-term immobilization. Cell Tissue Res 302, 235–241.
71Allen, DL, Linderman, JK, Roy, RR, et al. (1997) Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles. J Appl Physiol 83, 1857–1861.
72Schmalbruch, H & Lewis, DM (2000) Dynamics of nuclei of muscle fibers and connective tissue cells in normal and denervated rat muscles. Muscle Nerve 23, 617–626.
73Allen, DL, Linderman, JK, Roy, RR, et al. (1997) Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting. Am J Physiol 273, C579–C587.
74Marzetti, E, Hwang, JC, Lees, HA, et al. (2010) Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta 1800, 235–244.
75Powers, SK, Smuder, AJ & Judge, AR (2012) Oxidative stress and disuse muscle atrophy: cause or consequence? Curr Opin Clin Nutr Metab Care 15, 240–245.
76Darr, KC & Schultz, E (1989) Hindlimb suspension suppresses muscle growth and satellite cell proliferation. J Appl Physiol 67, 1827–1834.
77Matsuba, Y, Goto, K, Morioka, S, et al. (2009) Gravitational unloading inhibits the regenerative potential of atrophied soleus muscle in mice. Acta Physiol (Oxf) 196, 329–339.
78Mozdziak, PE, Truong, Q, Macius, A, et al. (1998) Hindlimb suspension reduces muscle regeneration. Eur J Appl Physiol Occup Physiol 78, 136–140.
79Shefer, G, Carmeli, E, Rauner, G, et al. (2008) Exercise running and tetracycline as means to enhance skeletal muscle stem cell performance after external fixation. J Cell Physiol 215, 265–275.
80Zhang, BT, Yeung, SS, Liu, Y, et al. (2010) The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension. BMC Cell Biol 11, 87.
81Van der Meer, SF, Jaspers, RT & Degens, H (2011) Is the myonuclear domain size fixed? J Musculoskelet Neuronal Interact 11, 286–297.
82Allen, DL, Monke, SR, Talmadge, RJ, et al. (1995) Plasticity of myonuclear number in hypertrophied and atrophied mammalian skeletal muscle fibers. J Appl Physiol 78, 1969–1976.
83Aravamudan, B, Mantilla, CB, Zhan, WZ, et al. (2006) Denervation effects on myonuclear domain size of rat diaphragm fibers. J Appl Physiol 100, 1617–1622.
84Tseng, BS, Kasper, CE & Edgerton, VR (1994) Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers. Cell Tissue Res 275, 39–49.
85Reynet, C & Kahn, CR (1993) Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans. Science 262, 1441–1444.
86Vaag, A (1999) On the pathophysiology of late onset non-insulin dependent diabetes mellitus. Current controversies and new insights. Dan Med Bull 46, 197–234.
87Handschin, C & Spiegelman, BM (2008) The role of exercise and PGC1α in inflammation and chronic disease. Nature 454, 463–469.
88Alibegovic, AC, Hojbjerre, L, Sonne, MP, et al. (2009) Impact of 9 days of bed rest on hepatic and peripheral insulin action, insulin secretion, and whole-body lipolysis in healthy young male offspring of patients with type 2 diabetes. Diabetes 58, 2749–2756.
89Alibegovic, AC, Hojbjerre, L, Sonne, MP, et al. (2010) Increased rate of whole body lipolysis before and after 9 days of bed rest in healthy young men born with low birth weight. Am J Physiol Endocrinol Metab 298, E555–E564.
90Alibegovic, AC, Sonne, MP, Hojbjerre, L, et al. (2010) The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest. Diabetes 59, 836–843.
91Dolkas, CB & Greenleaf, JE (1977) Insulin and glucose responses during bed rest with isotonic and isometric exercise. J Appl Physiol 43, 1033–1038.
92Hamburg, NM, McMackin, CJ, Huang, AL, et al. (2007) Physical inactivity rapidly induces insulin resistance and microvascular dysfunction in healthy volunteers. Arterioscler Thromb Vasc Biol 27, 2650–2656.
93Lipman, RL, Schnure, JJ, Bradley, EM, et al. (1970) Impairment of peripheral glucose utilization in normal subjects by prolonged bed rest. J Lab Clin Med 76, 221–230.
94Mikines, KJ, Richter, EA, Dela, F, et al. (1991) Seven days of bed rest decrease insulin action on glucose uptake in leg and whole body. J Appl Physiol 70, 1245–1254.
95Stuart, CA, Shangraw, RE, Prince, MJ, et al. (1988) Bed-rest-induced insulin resistance occurs primarily in muscle. Metabolism 37, 802–806.
96Tabata, I, Suzuki, Y, Fukunaga, T, et al. (1999) Resistance training affects GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest. J Appl Physiol 86, 909–914.
97Kimball, SR, Jurasinski, CV, Lawrence, JC Jr, et al. (1997) Insulin stimulates protein synthesis in skeletal muscle by enhancing the association of eIF-4E and eIF-4G. Am J Physiol 272, C754–C759.
98Stein, T, Schluter, M, Galante, A, et al. (2002) Energy metabolism pathways in rat muscle under conditions of simulated microgravity. J Nutr Biochem 13, 471.
99Koesterer, TJ, Dodd, SL & Powers, S (2002) Increased antioxidant capacity does not attenuate muscle atrophy caused by unweighting. J Appl Physiol 93, 1959–1965.
100Kondo, H, Miura, M & Itokawa, Y (1991) Oxidative stress in skeletal muscle atrophied by immobilization. Acta Physiol Scand 142, 527–528.
101Kondo, H, Miura, M, Nakagaki, I, et al. (1992) Trace element movement and oxidative stress in skeletal muscle atrophied by immobilization. Am J Physiol 262, E583–E590.
102Kondo, H, Miura, M & Itokawa, Y (1993) Antioxidant enzyme systems in skeletal muscle atrophied by immobilization. Pflugers Arch 422, 404–406.
103Kondo, H, Nakagaki, I, Sasaki, S, et al. (1993) Mechanism of oxidative stress in skeletal muscle atrophied by immobilization. Am J Physiol 265, E839–E844.
104Kondo, H, Nishino, K & Itokawa, Y (1994) Hydroxyl radical generation in skeletal muscle atrophied by immobilization. FEBS Lett 349, 169–172.
105Lambertucci, RH, Levada-Pires, AC, Rossoni, LV, et al. (2007) Effects of aerobic exercise training on antioxidant enzyme activities and mRNA levels in soleus muscle from young and aged rats. Mech Ageing Dev 128, 267–275.
106Lawler, JM, Song, W & Demaree, SR (2003) Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle. Free Radic Biol Med 35, 9–16.
107Candelario-Jalil, E, de Oliveira, AC, Graf, S, et al. (2007) Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroinflammation 4, 25.
108Murcia, MA & Martinez-Tome, M (2001) Antioxidant activity of resveratrol compared with common food additives. J Food Prot 64, 379–384.
109Agostini, F, Dalla, LL, Rittweger, J, et al. (2010) Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach. J Physiol 588, 5089–5104.
110Powers, SK, Kavazis, AN & McClung, JM (2007) Oxidative stress and disuse muscle atrophy. J Appl Physiol 102, 2389–2397.
111Crowe, AV, McArdle, A, McArdle, F, et al. (2007) Markers of oxidative stress in the skeletal muscle of patients on haemodialysis. Nephrol Dial Transplant 22, 1177–1183.
112Levine, S, Nguyen, T, Taylor, N, et al. (2008) Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med 358, 1327–1335.
113Stein, TP (2002) Space flight and oxidative stress. Nutrition 18, 867–871.
114Sacheck, JM, Hyatt, JP, Raffaello, A, et al. (2007) Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J 21, 140–155.
115Ikemoto, M, Okamura, Y, Kano, M, et al. (2002) A relative high dose of vitamin E does not attenuate unweighting-induced oxidative stress and ubiquitination in rat skeletal muscle. J Physiol Anthropol Appl Human Sci 21, 257–263.
116Sen, CK, Marin, E, Kretzschmar, M, et al. (1992) Skeletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization. J Appl Physiol 73, 1265–1272.
117Tauler, P, Aguilo, A, Gimeno, I, et al. (2006) Response of blood cell antioxidant enzyme defences to antioxidant diet supplementation and to intense exercise. Eur J Nutr 45, 187–195.
118Cai, J, Kang, Z, Liu, WW, et al. (2008) Hydrogen therapy reduces apoptosis in neonatal hypoxia–ischemia rat model. Neurosci Lett 441, 167–172.
119Nagano, K, Suzaki, E, Nagano, Y, et al. (2008) The activation of apoptosis factor in hindlimb unloading-induced muscle atrophy under normal and low-temperature environmental conditions. Acta Histochem 110, 505–518.
120Grune, T, Merker, K, Sandig, G, et al. (2003) Selective degradation of oxidatively modified protein substrates by the proteasome. Biochem Biophys Res Commun 305, 709–718.
121Bota, DA & Davies, KJ (2002) Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism. Nat Cell Biol 4, 674–680.
122Dukan, S, Farewell, A, Ballesteros, M, et al. (2000) Protein oxidation in response to increased transcriptional or translational errors. Proc Natl Acad Sci U S A 97, 5746–5749.
123Smuder, AJ, Kavazis, AN, Min, K, et al. (2011) Exercise protects against doxorubicin-induced oxidative stress and proteolysis in skeletal muscle. J Appl Physiol 110, 935–942.
124Whidden, MA, Smuder, AJ, Wu, M, et al. (2010) Oxidative stress is required for mechanical ventilation-induced protease activation in the diaphragm. J Appl Physiol 108, 1376–1382.
125Siu, PM, Pistilli, EE & Alway, SE (2008) Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading. J Appl Physiol 105, 1695–1705.
126Bar-Shai, M, Carmeli, E, Ljubuncic, P, et al. (2008) Exercise and immobilization in aging animals: the involvement of oxidative stress and NF-κB activation. Free Radic Biol Med 44, 202–214.
127Kramer, HF & Goodyear, LJ (2007) Exercise, MAPK, and NF-κB signaling in skeletal muscle. J Appl Physiol 103, 388–395.
128Powers, SK & Lennon, SL (1999) Analysis of cellular responses to free radicals: focus on exercise and skeletal muscle. Proc Nutr Soc 58, 1025–1033.
129Appell, HJ (1986) Morphology of immobilized skeletal muscle and the effects of a pre- and postimmobilization training program. Int J Sports Med 7, 6–12.
130Baker, JH & Matsumoto, DE (1988) Adaptation of skeletal muscle to immobilization in a shortened position. Muscle Nerve 11, 231–244.
131Bigard, AX, Merino, D, Lienhard, F, et al. (1997) Quantitative assessment of degenerative changes in soleus muscle after hindlimb suspension and recovery. Eur J Appl Physiol Occup Physiol 75, 380–387.
132Cai, D, Frantz, JD, Tawa, NE Jr, et al. (2004) IKKβ/NF-κB activation causes severe muscle wasting in mice. Cell 119, 285–298.
133Pistilli, EE, Jackson, JR & Alway, SE (2006) Death receptor-associated pro-apoptotic signaling in aged skeletal muscle. Apoptosis 11, 2115–2126.
134Lang, CH, Frost, RA, Nairn, AC, et al. (2002) TNF-α impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol Endocrinol Metab 282, E336–E347.
135Marzani, B, Balage, M, Venien, A, et al. (2008) Antioxidant supplementation restores defective leucine stimulation of protein synthesis in skeletal muscle from old rats. J Nutr 138, 2205–2211.
136Rieu, I, Magne, H, Savary-Auzeloux, I, et al. (2009) Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats. J Physiol 587, 5483–5492.
137Mitchell, PO & Pavlath, GK (2001) A muscle precursor cell-dependent pathway contributes to muscle growth after atrophy. Am J Physiol Cell Physiol 281, C1706–C1715.
138Oishi, Y, Ogata, T, Yamamoto, KI, et al. (2008) Cellular adaptations in soleus muscle during recovery after hindlimb unloading. Acta Physiol (Oxf) 192, 381–395.
139Childs, TE, Spangenburg, EE, Vyas, DR, et al. (2003) Temporal alterations in protein signaling cascades during recovery from muscle atrophy. Am J Physiol Cell Physiol 285, C391–C398.
140Washington, TA, White, JP, Davis, JM, et al. (2011) Skeletal muscle mass recovery from atrophy in IL-6 knockout mice. Acta Physiol (Oxf) 202, 657–669.
141Allen, DL, Sartorius, CA, Sycuro, LK, et al. (2001) Different pathways regulate expression of the skeletal myosin heavy chain genes. J Biol Chem 276, 43524–43533.
142Fernando, P, Kelly, JF, Balazsi, K, et al. (2002) Caspase 3 activity is required for skeletal muscle differentiation. Proc Natl Acad Sci U S A 99, 11025–11030.
143Sartorelli, V & Fulco, M (2004) Molecular and cellular determinants of skeletal muscle atrophy and hypertrophy. Sci STKE 2004, re11.
144Booth, FW (1982) Effect of limb immobilization on skeletal muscle. J Appl Physiol 52, 1113–1118.
145Hornberger, TA, Hunter, RB, Kandarian, SC, et al. (2001) Regulation of translation factors during hindlimb unloading and denervation of skeletal muscle in rats. Am J Physiol Cell Physiol 281, C179–C187.
146Reynolds, TH, Bodine, SC & Lawrence, JC Jr (2002) Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. J Biol Chem 277, 17657–17662.
147Lang, SM, Kazi, AA, Hong-Brown, L, et al. (2012) Delayed recovery of skeletal muscle mass following hindlimb immobilization in mTOR heterozygous mice. PLOS ONE 7, e38910.
148Anthony, JC, Anthony, TG & Layman, DK (1999) Leucine supplementation enhances skeletal muscle recovery in rats following exercise. J Nutr 129, 1102–1106.
149Anthony, TG, Anthony, JC, Yoshizawa, F, et al. (2001) Oral administration of leucine stimulates ribosomal protein mRNA translation but not global rates of protein synthesis in the liver of rats. J Nutr 131, 1171–1176.
150Koopman, R, Wagenmakers, AJ, Manders, RJ, et al. (2005) Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects. Am J Physiol Endocrinol Metab 288, E645–E653.
151Boirie, Y, Dangin, M, Gachon, P, et al. (1997) Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A 94, 14930–14935.
152Bos, C, Metges, CC, Gaudichon, C, et al. (2003) Postprandial kinetics of dietary amino acids are the main determinant of their metabolism after soy or milk protein ingestion in humans. J Nutr 133, 1308–1315.
153Farnfield, MM, Trenerry, C, Carey, KA, et al. (2009) Plasma amino acid response after ingestion of different whey protein fractions. Int J Food Sci Nutr 60, 476–486.
154Tada, O & Yokogoshi, H (2002) Effect of different dietary protein composition on skeletal muscle atrophy by suspension hypokinesia/hypodynamia in rats. J Nutr Sci Vitaminol (Tokyo) 48, 115–119.
155Brooks, N, Cloutier, GJ, Cadena, SM, et al. (2008) Resistance training and timed essential amino acids protect against the loss of muscle mass and strength during 28 days of bed rest and energy deficit. J Appl Physiol 105, 241–248.
156Brooks, NE, Cadena, SM, Vannier, E, et al. (2010) Effects of resistance exercise combined with essential amino acid supplementation and energy deficit on markers of skeletal muscle atrophy and regeneration during bed rest and active recovery. Muscle Nerve 42, 927–935.
157Paddon-Jones, D, Sheffield-Moore, M, Urban, RJ, et al. (2004) Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab 89, 4351–4358.
158Fitts, RH, Romatowski, JG, Peters, JR, et al. (2007) The deleterious effects of bed rest on human skeletal muscle fibers are exacerbated by hypercortisolemia and ameliorated by dietary supplementation. Am J Physiol Cell Physiol 293, C313–C320.
159Buse, MG & Reid, SS (1975) Leucine. A possible regulator of protein turnover in muscle. J Clin Invest 56, 1250–1261.
160Crozier, SJ, Kimball, SR, Emmert, SW, et al. (2005) Oral leucine administration stimulates protein synthesis in rat skeletal muscle. J Nutr 135, 376–382.
161Frexes-Steed, M, Lacy, DB, Collins, J, et al. (1992) Role of leucine and other amino acids in regulating protein metabolism in vivo. Am J Physiol 262, E925–E935.
162Anthony, JC, Anthony, TG, Kimball, SR, et al. (2000) Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. J Nutr 130, 139–145.
163Bolster, DR, Vary, TC, Kimball, SR, et al. (2004) Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylation. J Nutr 134, 1704–1710.
164Dardevet, D, Sornet, C, Balage, M, et al. (2000) Stimulation of in vitro rat muscle protein synthesis by leucine decreases with age. J Nutr 130, 2630–2635.
165Balage, M, Averous, J, Remond, D, et al. (2010) Presence of low-grade inflammation impaired postprandial stimulation of muscle protein synthesis in old rats. J Nutr Biochem 21, 325–331.
166Stein, TP, Donaldson, MR, Leskiw, MJ, et al. (2003) Branched-chain amino acid supplementation during bed rest: effect on recovery. J Appl Physiol 94, 1345–1352.
167Trappe, S, Creer, A, Slivka, D, et al. (2007) Single muscle fiber function with concurrent exercise or nutrition countermeasures during 60 days of bed rest in women. J Appl Physiol 103, 1242–1250.
168Trappe, S, Creer, A, Minchev, K, et al. (2008) Human soleus single muscle fiber function with exercise or nutrition countermeasures during 60 days of bed rest. Am J Physiol Regul Integr Comp Physiol 294, R939–R947.
169Chopard, A, Lecunff, M, Danger, R, et al. (2009) Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures. Physiol Genomics 38, 291–302.
170Baptista, IL, Leal, ML, Artioli, GG, et al. (2010) Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases. Muscle Nerve 41, 800–808.
171Huxtable, RJ (1992) Physiological actions of taurine. Physiol Rev 72, 101–163.
172Pierno, S, Liantonio, A, Camerino, GM, et al. (2012) Potential benefits of taurine in the prevention of skeletal muscle impairment induced by disuse in the hindlimb-unloaded rat. Amino Acids 43, 431–435.
173Johnston, AP, Burke, DG, MacNeil, LG, et al. (2009) Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance. J Strength Cond Res 23, 116–120.
174Ikemoto, M, Nikawa, T, Kano, M, et al. (2002) Cysteine supplementation prevents unweighting-induced ubiquitination in association with redox regulation in rat skeletal muscle. Biol Chem 383, 715–721.
175Cornelli, U (2009) Antioxidant use in nutraceuticals. Clin Dermatol 27, 175–194.
176Servais, S, Letexier, D, Favier, R, et al. (2007) Prevention of unloading-induced atrophy by vitamin E supplementation: links between oxidative stress and soleus muscle proteolysis? Free Radic Biol Med 42, 627–635.
177Brito, PM, Simoes, NF, Almeida, LM, et al. (2008) Resveratrol disrupts peroxynitrite-triggered mitochondrial apoptotic pathway: a role for Bcl-2. Apoptosis 13, 1043–1053.
178Das, S, Khan, N, Mukherjee, S, et al. (2008) Redox regulation of resveratrol-mediated switching of death signal into survival signal. Free Radic Biol Med 44, 82–90.
179Dani, C, Bonatto, D, Salvador, M, et al. (2008) Antioxidant protection of resveratrol and catechin in Saccharomyces cerevisiae. J Agric Food Chem 56, 4268–4272.
180Kode, A, Rajendrasozhan, S, Caito, S, et al. (2008) Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 294, L478–L488.
181Robb, EL, Winkelmolen, L, Visanji, N, et al. (2008) Dietary resveratrol administration increases MnSOD expression and activity in mouse brain. Biochem Biophys Res Commun 372, 254–259.
182Robb, EL, Page, MM, Wiens, BE, et al. (2008) Molecular mechanisms of oxidative stress resistance induced by resveratrol: specific and progressive induction of MnSOD. Biochem Biophys Res Commun 367, 406–412.
183Ryan, MJ, Jackson, JR, Hao, Y, et al. (2010) Suppression of oxidative stress by resveratrol after isometric contractions in gastrocnemius muscles of aged mice. J Gerontol A Biol Sci Med Sci 65, 815–831.
184Jackson, JR, Ryan, MJ, Hao, Y, et al. (2010) Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats. Am J Physiol Regul Integr Comp Physiol 299, R1572–R1581.
185Momken, I, Stevens, L, Bergouignan, A, et al. (2011) Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat. FASEB J 25, 3646–3660.
186Ota, N, Soga, S, Haramizu, S, et al. (2011) Tea catechins prevent contractile dysfunction in unloaded murine soleus muscle: a pilot study. Nutrition 27, 955–959.
187Appell, HJ, Duarte, JA & Soares, JM (1997) Supplementation of vitamin E may attenuate skeletal muscle immobilization atrophy. Int J Sports Med 18, 157–160.
188Arbogast, S, Smith, J, Matuszczak, Y, et al. (2007) Bowman-Birk inhibitor concentrate prevents atrophy, weakness, and oxidative stress in soleus muscle of hindlimb-unloaded mice. J Appl Physiol 102, 956–964.
189Farid, M, Reid, MB, Li, YP, et al. (2005) Effects of dietary curcumin or N-acetylcysteine on NF-κB activity and contractile performance in ambulatory and unloaded murine soleus. Nutr Metab (Lond) 2, 20.
190Freund, H, Atamian, S & Fischer, JE (1979) Chromium deficiency during total parenteral nutrition. JAMA 241, 496–498.
191Dong, F, Hua, Y, Zhao, P, et al. (2009) Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice. J Nutr Biochem 20, 992–999.
192Fetterman, JW Jr & Zdanowicz, MM (2009) Therapeutic potential of n-3 polyunsaturated fatty acids in disease. Am J Health Syst Pharm 66, 1169–1179.
193Gingras, AA, White, PJ, Chouinard, PY, et al. (2007) Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity. J Physiol 579, 269–284.
194Biolo, G, Ciocchi, B, Stulle, M, et al. (2007) Calorie restriction accelerates the catabolism of lean body mass during 2 wk of bed rest. Am J Clin Nutr 86, 366–372.
195Biolo, G, Agostini, F, Simunic, B, et al. (2008) Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest. Am J Clin Nutr 88, 950–958.
196Dreyer, HC, Drummond, MJ, Pennings, B, et al. (2008) Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab 294, E392–E400.
197Fujita, S, Dreyer, HC, Drummond, MJ, et al. (2007) Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol 582, 813–823.
198Stein, TP, Leskiw, MJ, Schluter, MD, et al. (1999) Energy expenditure and balance during spaceflight on the space shuttle. Am J Physiol 276, R1739–R1748.
199You, JS, Park, MN & Lee, YS (2010) Dietary fish oil inhibits the early stage of recovery of atrophied soleus muscle in rats via Akt-p70s6k signaling and PGF2α. J Nutr Biochem 21, 929–934.
200Chakravarthy, MV, Davis, BS & Booth, FW (2000) IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle. J Appl Physiol 89, 1365–1379.
201Suetta, C, Hvid, LG, Justesen, L, et al. (2009) Effects of aging on human skeletal muscle after immobilization and retraining. J Appl Physiol 107, 1172–1180.
202Fujita, S, Glynn, EL, Timmerman, KL, et al. (2009) Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism. Diabetologia 52, 1889–1898.
203Guillet, C, Prod'homme, M, Balage, M, et al. (2004) Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J 18, 1586–1587.
204Mosoni, L, Valluy, MC, Serrurier, B, et al. (1995) Altered response of protein synthesis to nutritional state and endurance training in old rats. Am J Physiol 268, E328–E335.
205Drummond, MJ, Dickinson, JM, Fry, CS, et al. (2012) Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab 302, E1113–E1122.
206Hvid, L, Aagaard, P, Justesen, L, et al. (2010) Effects of aging on muscle mechanical function and muscle fiber morphology during short-term immobilization and subsequent retraining. J Appl Physiol 109, 1628–1634.
207Dillon, EL, Sheffield-Moore, M, Paddon-Jones, D, et al. (2009) Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women. J Clin Endocrinol Metab 94, 1630–1637.
208Ferrando, AA, Paddon-Jones, D, Hays, NP, et al. (2010) EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr 29, 18–23.
209Altun, M, Besche, HC, Overkleeft, HS, et al. (2010) Muscle wasting in aged, sarcopenic rats is associated with enhanced activity of the ubiquitin proteasome pathway. J Biol Chem 285, 39597–39608.
210Piper, MD & Bartke, A (2008) Diet and aging. Cell Metab 8, 99–104.
211Altun, M, Bergman, E, Edstrom, E, et al. (2007) Behavioral impairments of the aging rat. Physiol Behav 92, 911–923.
212Dardevet, D, Sornet, C, Bayle, G, et al. (2002) Postprandial stimulation of muscle protein synthesis in old rats can be restored by a leucine-supplemented meal. J Nutr 132, 95–100.
213Katsanos, CS, Kobayashi, H, Sheffield-Moore, M, et al. (2006) A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab 291, E381–E387.
214Rieu, I, Sornet, C, Bayle, G, et al. (2003) Leucine-supplemented meal feeding for ten days beneficially affects postprandial muscle protein synthesis in old rats. J Nutr 133, 1198–1205.
215Rieu, I, Balage, M, Sornet, C, et al. (2006) Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 575, 305–315.
216Rieu, I, Balage, M, Sornet, C, et al. (2007) Increased availability of leucine with leucine-rich whey proteins improves postprandial muscle protein synthesis in aging rats. Nutrition 23, 323–331.
217Boirie, Y, Gachon, P, Corny, S, et al. (1996) Acute postprandial changes in leucine metabolism as assessed with an intrinsically labeled milk protein. Am J Physiol 271, E1083–E1091.
218Dangin, M, Boirie, Y, Garcia-Rodenas, C, et al. (2001) The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol Endocrinol Metab 280, E340–E348.
219Dangin, M, Boirie, Y, Guillet, C, et al. (2002) Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr 132, 3228S–3233S.
220Pennings, B, Boirie, Y, Senden, JM, et al. (2011) Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. Am J Clin Nutr 93, 997–1005.
221Wilkinson, SB, Tarnopolsky, MA, MacDonald, MJ, et al. (2007) Consumption of fluid skim milk promotes greater muscle protein accretion after resistance exercise than does consumption of an isonitrogenous and isoenergetic soy-protein beverage. Am J Clin Nutr 85, 1031–1040.
222Mitch, WE & Clark, AS (1984) Specificity of the effects of leucine and its metabolites on protein degradation in skeletal muscle. Biochem J 222, 579–586.
223Hao, Y, Jackson, JR, Wang, Y, et al. (2011) β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats. Am J Physiol Regul Integr Comp Physiol 301, R701–R715.
224Hsieh, LC, Chow, CJ, Chang, WC, et al. (2010) Effect of β-hydroxy-β-methylbutyrate on protein metabolism in bed-ridden elderly receiving tube feeding. Asia Pac J Clin Nutr 19, 200–208.