Skip to main content
Log in

The Molecular Bases of Training Adaptation

  • Review Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

Skeletal muscle is a malleable tissue capable of altering the type and amount of protein in response to disruptions to cellular homeostasis. The process of exerciseinduced adaptation in skeletal muscle involves a multitude of signalling mechanisms initiating replication of specific DNA genetic sequences, enabling subsequent translation of the genetic message and ultimately generating a series of amino acids that form new proteins. The functional consequences of these adaptations are determined by training volume, intensity and frequency, and the half-life of the protein. Moreover, many features of the training adaptation are specific to the type of stimulus, such as the mode of exercise. Prolonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fibre-type transformation and substrate metabolism. In contrast, heavy resistance exercise stimulates synthesis of contractile proteins responsible for muscle hypertrophy and increases in maximal contractile force output. Concomitant with the vastly different functional outcomes induced by these diverse exercise modes, the genetic and molecular mechanisms of adaptation are distinct. With recent advances in technology, it is now possible to study the effects of various training interventions on a variety of signalling proteins and early-response genes in skeletal muscle. Although it cannot presently be claimed that such scientific endeavours have influenced the training practices of elite athletes, these new and exciting technologies have provided insight into how current training techniques result in specific muscular adaptations, and may ultimately provide clues for future and novel training methodologies. Greater knowledge of the mechanisms and interaction of exercise-induced adaptive pathways in skeletal muscle is important for our understanding of the aetiology of disease, maintenance of metabolic and functional capacity with aging, and training for athletic performance. This article highlights the effects of exercise on molecular and genetic mechanisms of training adaptation in skeletal muscle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Table I
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Bouchard C, Malina R, Pérusse L, editors. On the horizon: molecular biology: a new vista for exercise physiology. In: Genetics of fitness and physical performance. Champaign (IL): Human Kinetics, 1997: 970x1050

  2. Izquierdo M, Ibanez J, Hakkinen K, et al. Maximal strength and power, muscle mass, endurance and serum hormones in weightlifters and road cyclists. J Sports Sci 2004; 22 (5): 465–78

    Article  Google Scholar 

  3. Mahoney DJ, Parise G, Melov S, et al. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB J 2005; 19 (11): 1498–500

    PubMed  CAS  Google Scholar 

  4. Bickel CS, Slade J, Mahoney E, et al. Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise. J Appl Physiol 2005; 98 (2): 482–8

    PubMed  CAS  Google Scholar 

  5. Yang Y, Creer A, Jemiolo B, et al. Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle. J Appl Physiol 2005; 98 (5): 1745–52

    Article  PubMed  CAS  Google Scholar 

  6. Pilegaard H, Ordway GA, Saltin B, et al. Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise. Am J Physiol Endocrinol Metab 2000; 279: E806–14

    PubMed  CAS  Google Scholar 

  7. Booth FW, Baldwin KM. Muscle plasticity: energy demand and supply processes. In: Rowell LB, Shepherd JT, editors. Handbook of physiology. Section 12. Exercise: regulation and integration of multiple systems. New York: Oxford University Press, 1996: 1075–123

    Google Scholar 

  8. Irrcher I, Adhihetty PJ, Joseph AM, et al. Regulation of mitochondrial biogenesis in muscle by endurance exercise. Sports Med 2003; 33 (11): 783–93

    Article  PubMed  Google Scholar 

  9. Zierath JR, Hawley JA. Skeletal muscle fiber type: influence on contractile and metabolic properties. PLoS Biol 2004; 2 (10): e348

    Article  PubMed  CAS  Google Scholar 

  10. Holloszy JO, Rennie MJ, Hickson RC, et al. Physiological consequences of the biochemical adaptations to endurance exercise. Ann N Y Acad Sci 1977; 301: 440–50

    Article  PubMed  CAS  Google Scholar 

  11. Rennie MJ, Wackerhage H, Spangenburg EE, et al. Control of the size of the human muscle mass. Ann Rev Physiol 2004; 66: 799–828

    Article  CAS  Google Scholar 

  12. Häkkinen K. Neuromuscular and hormonal adaptations during strength and power training: a review. J Sports Med Phys Fitness 1989; 29 (1): 9–26

    PubMed  Google Scholar 

  13. Ingalls CP. Nature vs nurture: can exercise really alter fibre type composition in human skeletal muscle. J Appl Physiol 2004; 97 (5): 1591–2

    Article  PubMed  Google Scholar 

  14. Williams RS, Neufer PD. Regulation of gene expression in skeletal muscle by contractile activity. In: Rowell LB, Shepherd JT, editors. Handbook of physiology. Section 12. Exercise: regulation and integration of multiple systems. New York: Oxford University Press, 1996: 1124–150

    Google Scholar 

  15. Alenghat FJ, Ingber DE. Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins. Sci STKE 2002; (119): PE6

    Google Scholar 

  16. Kumar A, Chaudhry I, Reid MB, et al. Distinct signaling pathways are activated in response to mechanical stress applied axially and transversely to skeletal muscle fibers. J Biol Chem 2002; 277 (48): 46493–503

    Article  PubMed  CAS  Google Scholar 

  17. Hornberger TA, Armstrong DD, Koh TJ, et al. Intracellular stretch: implications for mechanotransduction. Am J Physiol Cell Physiol 2005; 288 (1): C185–94

    PubMed  CAS  Google Scholar 

  18. Spriet LL. Regulation of skeletal muscle fat oxidation during exercise in humans. Med Sci Sports Exerc 2002; 34 (9): 1477–84

    Article  PubMed  CAS  Google Scholar 

  19. Schertzer JD, Green HJ, Fowles JR, et al. Effects of prolonged exercise and recovery on sarcoplasmic reticulum Ca2+ cycling properties in rat muscle homogenates. Acta Physiol Scand 2004; 180: 195–208

    Article  PubMed  CAS  Google Scholar 

  20. Matsunaga S, Inashima S, Tsuchimochi H, et al. Altered sarcoplasmic reticulum function in rat diaphragm after high-intensity exercise. Acta Physiol Scand 2002; 176: 227–32

    Article  PubMed  CAS  Google Scholar 

  21. Holloway GP, Green HJ, Duhamel TA, et al. Muscle sarcoplasmic reticulum Ca2+ cycling adaptations during 16h of heavy intermittent cycle exercise. J Appl Physiol 2005; 99 (3): 836–43

    Article  PubMed  CAS  Google Scholar 

  22. Baar K, Esser K. Phosphorylation of p70S6k correlates with increased skeletal muscle mass following resistance exercise. Am J Physiol Cell Physiol 1999; 276 (45): C120–7

    CAS  Google Scholar 

  23. Chin ER. Role of Ca2+/calmodulin-dependent kinases in skeletal muscle plasticity. J Appl Physiol 2005; 99 (2): 414–23

    Article  PubMed  CAS  Google Scholar 

  24. Smith MA, Reid MB. Redox modulation of contractile function in respiratory and limb skeletal muscle. Resp Physiol Neurobiol New Direct Exerc Physiol 2006; 151 (2-3): 229–41

    CAS  Google Scholar 

  25. Arbogast S, Reid MB. Oxidant activity in skeletal muscle fibers is influenced by temperature, CO2 level, and muscle-derived nitric oxide. Am J Physiol Regul Integr Comp Physiol 2004; 287 (4): R698–705

    Article  PubMed  CAS  Google Scholar 

  26. Carrero P, Okamoto K, Coumailleau P, et al. Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor α. Mol Cell Biol 2000; 20 (1): 402–15

    Article  PubMed  CAS  Google Scholar 

  27. Jindra M, Gaziova I, Uhlirova M, et al. Coactivator MBF1 preserves the redox-dependent AP-1 activity during oxidative stress in Drosophila. EMBO J 2004; 23 (17): 3538–47

    Article  PubMed  CAS  Google Scholar 

  28. Hawley JA, Zierath J. Integration of metabolic and mitogenic signal transduction in skeletal muscle. Exerc Sport Sci Rev 2004; 32 (1): 4–8

    Article  PubMed  Google Scholar 

  29. Sakamoto K, Goodyear LJ. Exercise effects on muscle insulin signaling and action (invited review): intracellular signaling in contracting skeletal muscle. J Appl Physiol 2002; 93 (1): 369–83

    PubMed  CAS  Google Scholar 

  30. Ferguson RA, Ball D, Krustrup P, et al. Muscle oxygen uptake and energy turnover during dynamic exercise at different contraction frequencies in humans. J Physiol (Lond) 2001; 536 (1): 261–71

    Article  CAS  Google Scholar 

  31. Ivy JL, Chi MM, Hintz CS, et al. Progressive metabolite changes in individual human muscle fibers with increasing work rates. Am J Physiol Cell Physiol 1987; 252 (6): C630–9

    CAS  Google Scholar 

  32. Krustrup P, Ferguson RA, Kjar M, et al. ATP and heat production in human skeletal muscle during dynamic exercise: higher efficiency of anaerobic than aerobic ATP resynthesis. J Physiol (Lond) 2003; 549 (1): 255–69

    Article  CAS  Google Scholar 

  33. Hardie DG, Sakamoto K. AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology 2006; 21 (1): 48–60

    Article  PubMed  CAS  Google Scholar 

  34. Aschenbach WG, Sakamoto K, Goodyear LJ. Adenosine monophosphate-activated protein kinase, metabolism and exercise. Sports Med 2004; 34 (2): 91–103

    Article  PubMed  Google Scholar 

  35. Jorgensen SB, Richter EA, Wojtaszewski JFP. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise. J Physiol (Lond) 2006; 574 (1): 17–31

    Article  CAS  Google Scholar 

  36. Hayashi T, Hirshman M, Kurth E, et al. Evidence for 5’-AMP activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 1998; 47 (8): 1369–73

    Article  PubMed  CAS  Google Scholar 

  37. Musi N, Hayashi T, Fujii N, et al. AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle. Am J Physiol Endocrinol Metab 2001; 280 (5): E677–84

    PubMed  CAS  Google Scholar 

  38. Nakano M, Hamada T, Hayashi T, et al. Isoform-specific activation of 5’adenosine monophosphate-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-a-d-ribonucleoside at a physiological level activates glucose transport and increases glucose transporter 4 in mouse skeletal muscle. Metabolism 2006; 55 (3): 300–8

    Article  PubMed  CAS  Google Scholar 

  39. Kaushik VK, Young ME, Dean DJ, et al. Regulation of fatty acid oxidation and glucose metabolism in rat soleus muscle:effects of AICAR. Am J Physiol Endocrinol Metab 2001; 281 (2): E335–40

    PubMed  CAS  Google Scholar 

  40. Lee JL, Kim M, Park H-S, et al. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARa and PGC-1. Biochem Biophys Res Commun 2006; 340: 291–5

    Article  PubMed  CAS  Google Scholar 

  41. Terada S, Kawanaka K, Goto M, et al. Effects of high-intensity intermittent swimming on PGC-1a protein expression in rat skeletal muscle. Acta Physiol Scand 2005; 184 (1): 59–65

    Article  PubMed  CAS  Google Scholar 

  42. Jorgensen SB, Wojtaszewski JFP, Viollet B, et al. Effects of a AMPK knockout on exercise-induced gene activation in mouse skeletal muscle. FASEB J 2005; 19 (9): 1146–8

    PubMed  Google Scholar 

  43. Bolster DR, Crozier SJ, Kimball SR, et al. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 2002; 277 (27): 23977–80

    Article  PubMed  CAS  Google Scholar 

  44. Toyoda T, Tanaka S, Ebihara K, et al. Low-intensity contraction activates the a1-isoform of 5’-AMP-activated protein kinase in rat skeletal muscle. Am J Physiol Endocrinol Metab 2006; 290 (3): E583–90

    Article  PubMed  CAS  Google Scholar 

  45. Wojtaszewski JFP, Birk JB, Frosig C, et al. 5’AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes. J Physiol (Lond) 2005; 564 (2): 563–73

    Article  CAS  Google Scholar 

  46. Atherton PJ, Babraj JA, Smith K, et al. Selective activation of AMPK-PGC-1a; or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 2005; 19 (7): 786–8

    PubMed  CAS  Google Scholar 

  47. Durante PE, Mustard KJ, Park S-H, et al. Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles. Am J Physiol Endocrinol Metab 2002; 283 (1): E178–86

    PubMed  CAS  Google Scholar 

  48. FrØsig C, JØrgensen SB, Hardie DG, et al. 5’-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle. Am J Physiol Endocrinol Metab 2004; 286: E411-7

    Article  PubMed  Google Scholar 

  49. Hurst D, Taylor EB, Cline TD, et al. AMP-activated protein kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of sedentary and endurance trained rats. Am J Physiol Endocrinol Metab 2005; 289 (4): E710–15

    Article  PubMed  CAS  Google Scholar 

  50. McConell GK, Lee-Young RS, Chen Z-P, et al. Short-term exercise training in humans reduces AMPK signalling during prolonged exercise independent of muscle glycogen. J Physiol (Lond) 2005; 568 (2): 665–76

    Article  CAS  Google Scholar 

  51. Nielsen JN, Mustard KJW, Graham DA, et al. 5’-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle. J Appl Physiol 2003; 94 (2): 631–41

    PubMed  CAS  Google Scholar 

  52. Taylor EB, Lamb JD, Hurst RW, et al. Endurance training increases skeletal muscle LKB1 and PGC-1a protein abundance: effects of time and intensity. Am J Physiol Endocrinol Metab 2005; 289 (6): E960–8

    Article  PubMed  CAS  Google Scholar 

  53. Yu M, Stepto NK, Chibalin AV, et al. Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise. J Physiol 2003; 546 (2): 327–35

    Article  PubMed  CAS  Google Scholar 

  54. Rasmussen BB, Winder WW. Effect of exercise intensity on skeletal muscle malonyl-CoA and acetyl-CoA carboxylase. J Appl Physiol 1997; 83 (4): 1104–9

    PubMed  CAS  Google Scholar 

  55. Chen Z-P, Stephens TJ, Murthy S, et al. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes 2003; 52 (9): 2205–12

    Article  PubMed  CAS  Google Scholar 

  56. Wadley GD, Lee-Young RS, Canny BJ, et al. Effect of exercise intensity and hypoxia on skeletal muscle AMPK signaling and substrate metabolism in humans. Am J Physiol Endocrinol Metab 2006; 290 (4): E694–702

    Article  PubMed  CAS  Google Scholar 

  57. Clark SA, Chen Z-P, Murphy KT, et al. Intensified exercise training does not alter AMPK signaling in human skeletal muscle. Am J Physiol Endocrinol Metab 2004; 286 (5): E737–43

    Article  PubMed  CAS  Google Scholar 

  58. Chen Z-P, McConell GK, Michell BJ, et al. AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. Am J Physiol Endocrinol Metab 2000; 279 (5): E1202–6

    PubMed  CAS  Google Scholar 

  59. Dreyer HC, Fujita S, Cadenas JG, et al. Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J Physiol C475-84 (Lond) 2006; 576 (Pt 2): 613–24

    Article  CAS  Google Scholar 

  60. Koopman R, Zorenc AHG, Gransier RJJ, et al. Increase in S6K1 phosphorylation in human skeletal muscle following resistance exercise occurs mainly in type II muscle fibers. Am J Physiol Endocrinol Metab 2006; 290 (6): E1245–52

    Article  PubMed  CAS  Google Scholar 

  61. Coffey VG, Zhong Z, Shield A, et al. Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. FASEB J 2005; 20 (1): 190–2

    PubMed  Google Scholar 

  62. Rose AJ, Hargreaves M. Exercise increases Ca2+-calmodulin dependent protein kinase II activity in human skeletal muscle. J Physiol (Lond) 2003; 553 (1): 303–9

    Article  CAS  Google Scholar 

  63. Wu H, Kanatous SB, Thurmond FA, et al. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 2002; 296 (5566): 349–52

    Article  PubMed  CAS  Google Scholar 

  64. Fluck M, Waxham MN, Hamilton MT, et al. Skeletal muscle Ca2+-independent kinase activity increases during either hypertrophy or running. J Appl Physiol 2000; 88 (1): 352–8

    PubMed  CAS  Google Scholar 

  65. Rose AJ, Kiens B, Richter EA. Ca2+-calmodulin dependent protein kinase expression and signalling in skeletal muscle during exercise. J Physiol (Lond) 2006; 574 (Pt 3): 889–903

    Article  CAS  Google Scholar 

  66. Liu Y, Shen T, Randall WR, et al. Signaling pathways in activity-dependent fiber type plasticity in adult skeletal muscle. J Muscle Res Cell Motil 2005; 26 (1): 13–21

    Article  PubMed  CAS  Google Scholar 

  67. Michel RN, Dunn SE, Chin ER. Calcineurin and skeletal muscle growth. Proc Nutr Soc 2004; 63 (2): 341–9

    Article  PubMed  CAS  Google Scholar 

  68. Sakuma K, Nishikawa J, Nakao R, et al. Calcineurin is a potent regulator for skeletal muscle regeneration by association with NFATc1 and GATA-2. Acta Neuropathol 2003; 105 (3): 271–80

    PubMed  CAS  Google Scholar 

  69. Musaro A, McCullagh KJA, Naya FJ, et al. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Nature 1999; 400 (6744): 581–5

    Article  PubMed  CAS  Google Scholar 

  70. Dunn SE, Burns JL, Michel RN. Calcineurin is required for skeletal muscle hypertrophy. J Biol Chem 1999; 274 (31): 21908–12

    Google Scholar 

  71. Scicchitano BM, Spath L, Musaro A, et al. Vasopressin-dependent myogenic cell differentiation is mediated by both Ca2+/calmodulin-dependent kinase and calcineurin pathways. Mol Biol Cell 2005; 16 (8): 3632–41

    Article  PubMed  CAS  Google Scholar 

  72. Dunn SE, Chin ER, Michel RN. Matching of calcineurin activity to upstream effectors is critical for skeletal muscle fiber growth. J Cell Biol 2000; 151 (3): 663–72

    Article  PubMed  CAS  Google Scholar 

  73. Naya FJ, Mercer B, Shelton J, et al. Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo. J Biol Chem 2000; 275 (7): 4545–8

    Article  PubMed  CAS  Google Scholar 

  74. Parsons SA, Millay DP, Wilkins BJ, et al. Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber type switching but not hypertrophy. J Biol Chem 2004; 279 (25): 26192–200

    Article  PubMed  CAS  Google Scholar 

  75. Talmadge R, Otis J, Rittler M, et al. Calcineurin activation influences muscle phenotype in a muscle-specific fashion. BMC Cell Biol 2004; 5: 28

    Article  PubMed  CAS  Google Scholar 

  76. Wu H, Naya F, McKinsey T, et al. MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. EMBO J 2000; 19 (9): 1963–73

    Article  PubMed  CAS  Google Scholar 

  77. Chin ER, Olson EN, Richardson JA, et al. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Gene Dev 1998; 12 (16): 2499–509

    Article  PubMed  CAS  Google Scholar 

  78. Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 2005; 37 (10): 1974–84

    Article  PubMed  CAS  Google Scholar 

  79. Taniguchi C, Emanuelli B, Kahn C. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 2006; 7 (2): 85–96

    Article  PubMed  CAS  Google Scholar 

  80. Vandenburgh HH, Karlisch P, Shansky J, et al. Insulin and IGFI induce pronounced hypertrophy of skeletal myofibers in tissue culture. Am J Physiol Cell Physiol 1991; 260 (3): C475–84

    CAS  Google Scholar 

  81. Latres E, Amini AR, Amini AA, et al. Insulin-like growth factor-1 (IGF-1) inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem 2005; 280 (4): 2737-44

    Article  PubMed  CAS  Google Scholar 

  82. Stitt TN, Drujan D, Clarke BA, et al. The IGF/PI3K/Akt path-way prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 2004; 14: 395–403

    Article  PubMed  CAS  Google Scholar 

  83. Chakravarthy MV, Davis BS, Booth FW. IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle. J Appl Physiol 2000; 89: 1365–79

    PubMed  CAS  Google Scholar 

  84. Rommel C, Bodine SC, Clarke BA, et al. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/ mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 2001; 3: 1009–13

    Article  PubMed  CAS  Google Scholar 

  85. Glass DJ. Molecular mechanisms modulating muscle mass. Trends Mol Med 2003; 9 (8): 344–50

    Article  PubMed  CAS  Google Scholar 

  86. Nader GA. Molecular determinants of skeletal muscle mass: getting the ‘AKT’ together. Int J Biochem Cell Biol 2005; 37 (10): 1985–96

    Article  PubMed  CAS  Google Scholar 

  87. Sarbassov DD, Guertin DA, Ali SM, et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307 (5712): 1098–101

    Article  PubMed  CAS  Google Scholar 

  88. Bodine SC, Stitt TN, Gonzalez M, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 2001; 3: 1014–9

    Article  PubMed  CAS  Google Scholar 

  89. Bruss MD, Arias EB, Lienhard GE, et al. Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity. Diabetes 2005; 54 (1): 41–50

    Article  PubMed  CAS  Google Scholar 

  90. Cai S-L, Tee AR, Short JD, et al. Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning. J Cell Biol 2006; 173 (2): 279–89

    Article  PubMed  CAS  Google Scholar 

  91. Inoki K, Li Y, Zhu T, et al. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002; 4 (9): 648–57

    Article  PubMed  CAS  Google Scholar 

  92. Nader GA, McLoughlin TJ, Esser KA. MTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators. Am J Physiol Cell Physiol 2005; 289 (6): C1457–65

    Article  PubMed  CAS  Google Scholar 

  93. Lai K-MV, Gonzalez M, Poueymirou WT, et al. Conditional activation of Akt in adult skeletal muscle induces rapid hypertrophy. Mol Cell Biol 2004; 24 (21): 9295–304

    Article  PubMed  CAS  Google Scholar 

  94. Hahn-Windgassen A, Nogueira V, Chen C-C, et al. Akt activvates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem 2005; 280 (37): 32081–9

    Article  PubMed  CAS  Google Scholar 

  95. Vyas DR, Spangenburg EE, Abraha TW, et al. GSK-3β negatively regulates skeletal myotube hypertrophy. Am J Physiol Cell Physiol 2002; 283 (2): C545–51

    PubMed  CAS  Google Scholar 

  96. Tee AR, Fingar DC, Manning BD, et al. Tuberous sclerosis complex-1 and-2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated down stream signaling. PNAS 2002; 99 (21): 13571–6

    Article  PubMed  CAS  Google Scholar 

  97. Rena G, Woods YL, Prescott AR, et al. Two novel phosphorylation sites on FKHR that are critical for its nuclear exclusion. EMBO J 2002; 21 (9): 2263–71

    Article  PubMed  CAS  Google Scholar 

  98. Bolster DR, Kubica N, Crozier SJ, et al. Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle. J Physiol (Lond) 2003; 553 (1): 213–20

    Article  CAS  Google Scholar 

  99. Wilson C, Hargreaves M, Howlett KF. Exercise does not alter subcellular localization, but increases phosphorylation of insulin-signaling proteins in human skeletal muscle. Am J Physiol Endocrinol Metab 2006; 290 (2): E341–6

    Article  PubMed  CAS  Google Scholar 

  100. Sakamoto K, Arnolds DEW, Ekberg I, et al. Exercise regulates Akt and glycogen synthase kinase-3 activities in human skeletal muscle. Biochem Biophys Res Commun 2004; 319 (2): 419–25

    Article  PubMed  CAS  Google Scholar 

  101. Thorell A, Hirshman MF, Nygren J, et al. Exercise and insulin cause GLUT-4 translocation in human skeletal muscle. Am J Physiol Endocrinol Metab 1999; 277 (4): E733–41

    CAS  Google Scholar 

  102. Widegren U, Jiang XJ, Krook A, et al. Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle. FASEB J 1998; 12: 1379–89

    PubMed  CAS  Google Scholar 

  103. Creer A, Gallagher P, Slivka D, et al. Influence of muscle glycogen availability on ERK1/2 and Akt signaling after resistance exercise in human skeletal muscle. J Appl Physiol 2005; 99 (3): 950–6

    Article  PubMed  CAS  Google Scholar 

  104. Leger B, Cartoni R, Praz M, et al. Akt signalling through GSK-3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol (Lond) 2006; 576 (Pt 3): 923–33

    Article  CAS  Google Scholar 

  105. Eliasson J, Elfegoun T, Nilsson J, et al. Maximal lengthening contractions increase p70S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. Am J Physiol Endocrinol Metab 2006; 291 (6): E1197–205

    Article  PubMed  CAS  Google Scholar 

  106. Williamson DL, Kubica N, Kimball SR, et al. Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscle. J Physiol (Lond) 2006; 573 (2): 497–510

    Article  CAS  Google Scholar 

  107. Reynolds TH, Reid P, Larkin LM, et al. Effects of aerobic exercise training on the protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway in aged skeletal muscle. Exp Gerontol 2004; 39 (3): 379–85

    Article  PubMed  CAS  Google Scholar 

  108. Krisan AD, Collins DE, Crain AM, et al. Resistance training enhances components of the insulin signaling cascade in normal and high-fat-fed rodent skeletal muscle. J Appl Physiol 2004; 96 (5): 1691–700

    Article  PubMed  CAS  Google Scholar 

  109. Sakamoto K, Aschenbach WG, Hirshman MF, et al. Akt signaling in skeletal muscle: regulation by exercise and passive stretch. Am J Physiol Endocrinol Metab 2003; 285 (5): E1081–8

    PubMed  CAS  Google Scholar 

  110. Markuns JF, Wojtaszewski JFP, Goodyear LJ. Insulin and exercise decrease glycogen synthase kinase-3 activity by different mechanisms in rat skeletal muscle. J Biol Chem 1999; 274 (35): 24896–900

    Article  PubMed  CAS  Google Scholar 

  111. Wojtaszewski JFP, Higaki Y, Hirshman MF, et al. Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice. J Clin In 1999; 104 (9): 1257–64

    CAS  Google Scholar 

  112. Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005; 17 (6): 596–603

    Article  PubMed  CAS  Google Scholar 

  113. Kim D-H, Sarbassov DD, Ali SM, et al. G[β]L, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 2003; 11 (4): 895–904

    Article  PubMed  CAS  Google Scholar 

  114. Sarbassov DD, Ali SM, Sengupta S, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22 (2): 159–68

    Article  PubMed  CAS  Google Scholar 

  115. Park I-H, Erbay E, Nuzzi P, et al. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1. Exp Cell Res 2005; 309 (1): 211–9

    Article  PubMed  CAS  Google Scholar 

  116. Sarbassov DD, Ali SM, Kim D-H, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 2004; 14 (14): 1296–302

    Article  PubMed  CAS  Google Scholar 

  117. Wang X, Beugnet A, Murakami M, et al. Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins. Mol Cell Biol 2005; 25 (7): 2558–72

    Article  PubMed  CAS  Google Scholar 

  118. Manning BD, Cantley LC. Rheb fills a GAP between TSC and TOR. Trends Biochem Sci 2003; 28 (11): 573–6

    Article  PubMed  CAS  Google Scholar 

  119. Garami A, Zwartkruis FJT, Nobukuni T, et al. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell 2003; 11 (6): 1457–66

    Article  PubMed  CAS  Google Scholar 

  120. Ohanna M, Sobering AK, Lapointe T, et al. Atrophy of S6K1-/skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol 2005; 7 (3): 286–94

    Article  PubMed  CAS  Google Scholar 

  121. Ali SM, Sabatini DM. Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site. J Biol Chem 2005; 280 (20): 19445–8

    Article  PubMed  CAS  Google Scholar 

  122. Ruvinsky I, Meyuhas O. Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 2006; 31 (6): 342–8

    Article  PubMed  CAS  Google Scholar 

  123. Thomson DM, Gordon SE. Impaired overload-induced muscle growth is associated with diminished translational signaling in aged rat fast-twitch skeletal muscle. J Physiol (Lond) 2006; 574 (Pt 1): 291–305

    Article  CAS  Google Scholar 

  124. Reynolds TH IV, Bodine SC, et al. Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. J Biol Chem 2002; 277 (20): 17657–62

    Article  PubMed  CAS  Google Scholar 

  125. Parkington JD, LeBrasseur NK, Siebert AP, et al. Contraction-mediated mTOR, p70S6k, and ERK1/2 phosphorylation in aged skeletal muscle. J Appl Physiol 2004; 97 (1): 243–8

    Article  PubMed  CAS  Google Scholar 

  126. Parkington JD, Siebert AP, LeBrasseur NK, et al. Differential activation of mTOR signaling by contractile activity in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2003; 285 (5): R1086–90

    PubMed  CAS  Google Scholar 

  127. Schieke SM, Phillips D, McCoy JP Jr, et al. The mTOR pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem 2006; 281 (37): 27643–52

    Article  PubMed  CAS  Google Scholar 

  128. Bolster DR, Kimball SR, Jefferson LS. Translational control mechanisms modulate skeletal muscle gene expression during hypertrophy. Exerc Sport Sci Rev 2003; 31 (3): 111–6

    Article  PubMed  Google Scholar 

  129. Shima H, Pende M, Chen Y, et al. Disruption of the p70(s6k)/ p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J 1998; 17 (22): 6649–59

    Article  PubMed  CAS  Google Scholar 

  130. Richter JD, Sonenberg N. Regulation of cap-dependent translation by eIF4E inhibitory proteins.Nature 2005; 433 (7025): 477–80

    Article  PubMed  CAS  Google Scholar 

  131. Nader GA, Esser KA. Intracellular signaling specificity in skeletal muscle in response to different modes of exercise. J Appl Physiol 2001; 90: 1936–42

    PubMed  CAS  Google Scholar 

  132. Karlsson HKR, Nilsson P-A, Nilsson J, et al. Branched-chain amino acids increase p70S6k phosphorylation in human skeletal muscle after resistance exercise. Am J Physiol Endocrinol Metab 2004; 287 (1): E1–7

    Article  PubMed  CAS  Google Scholar 

  133. Kubica N, Bolster DR, Farrell PA, et al. Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2Be mRNA in a mammalian target of rapamycin-dependent manner. J Biol Chem 2005; 280 (9): 7570–80

    Article  PubMed  CAS  Google Scholar 

  134. Hornberger TA, Mateja RD, Chin ER, et al. Aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle. J Appl Physiol 2005; 98 (4): 1562–6

    Article  PubMed  CAS  Google Scholar 

  135. Spangenburg EE, McBride TA. Inhibition of stretch-activated channels during eccentric muscle contraction attenuates p70S6K activation. J Appl Physiol 2006; 100 (1): 129–35

    Article  PubMed  CAS  Google Scholar 

  136. Jackman RW, Kandarian SC. The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol 2004; 287 (4): C834–43

    Article  PubMed  CAS  Google Scholar 

  137. Fernandez-Celemin L, Pasko N, Blomart V, et al. Inhibition of muscle insulin-like growth factor I expression by tumor necrosis factor-α. Am J Physiol Endocrinol Metab 2002; 283 (6): E1279–90

    PubMed  CAS  Google Scholar 

  138. Garcia-Martinez C, Agell N, Llovera M, et al. Tumour necrosis factor-[α] increases the ubiquitinization of rat skeletal muscle proteins. FEBS Lett 1993; 323 (3): 211–4

    Article  PubMed  CAS  Google Scholar 

  139. Lang CH, Krawiec BJ, Huber D, et al. Sepsis and inflammatory insults downregulate IGFBP-5, but not IGFBP-4, in skeletal muscle via a TNF-dependent mechanism. Am J Physiol Regul Integr Comp Physiol 2006; 290 (4): R963–72

    Article  PubMed  CAS  Google Scholar 

  140. Williamson DL, Kimball SR, Jefferson LS. Acute treatment with TNF-α attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism. Am J Physiol Endocrinol Metab 2005; 289 (1): E95–104

    Article  PubMed  CAS  Google Scholar 

  141. Langen RCJ, Van Der Velden JLJ, Schols AMWJ, et al. Tumor necrosis factor-α inhibits myogenic differentiation through MyoD protein destabilization. FASEB J 2004; 18 (2): 227–37

    Article  PubMed  CAS  Google Scholar 

  142. Vashisht Gopal Y, Arora T, Van Dyke M. Tumor necrosis factor-α depletes histone deacetylase 1 protein through IKK2. EMBO Rep 2006; 7 (3): 291–6

    Article  CAS  Google Scholar 

  143. Del Aguila LF, Claffey KP, Kirwan JP. TNF-a impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. Am J Physiol Endocrinol Metab 1999; 276 (5): E849–55

    Google Scholar 

  144. Plomgaard P, Bouzakri K, Krogh-Madsen R, et al. Tumor necrosis factor-a induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. Diabetes 2005; 54 (10): 2939–45

    Article  PubMed  CAS  Google Scholar 

  145. de Alvaro C, Teruel T, Hernandez R, et al. Tumor necrosis factor α produces insulin resistance in skeletal muscle by activation of inhibitor κB kinase in a p38 MAPK-dependent manner. J Biol Chem 2004; 279 (17): 17070–8

    Article  PubMed  CAS  Google Scholar 

  146. Li Y-P, Lecker SH, Chen Y, et al. TNF-a increases ubiquitin conjugating activity in skeletal muscle by up-regulating UbcH2/E220k. FASEB J 2003; 17 (9): 1048–57

    Article  PubMed  CAS  Google Scholar 

  147. Li Y-P, Chen Y, John J, et al. TNF-a acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J 2005; 19 (3): 362–70

    Article  PubMed  CAS  Google Scholar 

  148. Lang CH, Frost RA, Nairn AC, et al. TNF-a impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol Endocrinol Metab 2002; 282 (2): E336–47

    PubMed  CAS  Google Scholar 

  149. Sriwijitkamol A, Christ-Roberts C, Berria R, et al. Reduced skeletal muscle inhibitor of Bß content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training. Diabetes 2006; 55 (3): 760–7

    Article  PubMed  CAS  Google Scholar 

  150. Ostrowski K, Rohde T, Asp S, et al. Pro-and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 1999; 515 (1): 287–91

    Article  PubMed  CAS  Google Scholar 

  151. Del Aguila LF, Krishnan RK, Ulbrecht JS, et al. Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle. Am J Physiol Endocrinol Metab 2000; 279 (1): E206–12

    PubMed  Google Scholar 

  152. Amada K, Vannier E, Sacheck JM, et al. Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise. FASEB J 2004; 19 (2): 264–6

    Google Scholar 

  153. Chen ZJ. Ubiquitin signalling in the NF-[κ]B pathway. Nat CellBiol 2005; 7 (8): 758–65

    Article  PubMed  CAS  Google Scholar 

  154. Chen ZJ, Bhoj V, Seth RB. Ubiquitin, TAK1 and IKK: is there a connection? Cell Death Differ 2006; 13 (5): 687–92

    Article  PubMed  CAS  Google Scholar 

  155. Tergaonkar V, Correa RG, Ikawa M, et al. Distinct roles of I[κ]B proteins in regulating constitutive NF-[κ]B activity. Nat Cell Biol 2005; 7 (9): 921–3

    Article  PubMed  CAS  Google Scholar 

  156. Alkalay I, Yaron A, Hatzubai A, et al. Stimulation-dependent IκBa phosphorylation marks the NF-κB inhibitor for degradation via the ubiquitin-proteasome pathway. PNAS 1995; 92 (23): 10599–603

    Article  PubMed  CAS  Google Scholar 

  157. Scherer D, Brockman J, Chen Z, et al. Signal-induced degradation of IκBa requires site-specific ubiquitination. PNAS 1995; 92 (24): 11259–63

    Article  PubMed  CAS  Google Scholar 

  158. Chen Z, Hagler J, Palombella V, et al. Signal-induced site-specific phosphorylation targets IκBa to the ubiquitin proteasome pathway. Gene Dev 1995; 9 (13): 1586–97

    Article  PubMed  CAS  Google Scholar 

  159. Cai D, Frantz JD, Tawa J, et al. IKK[ß]/NF-[κ]B activation causes severe muscle wasting in mice. Cell 2004; 119 (2): 285–98

    Article  PubMed  CAS  Google Scholar 

  160. Hunter RB, Stevenson E, Koncarevic A, et al. Activation of an alternative NF-;AB pathway in skeletal muscle during disuse atrophy. FASEB J 2002; 16 (6): 529–38

    Article  PubMed  CAS  Google Scholar 

  161. Kumar A, Boriek AM. Mechanical stress activates the nuclear factor-κB pathway in skeletal muscle fibers: a possible role in Duchenne muscular dystrophy. FASEB J 2003; 17 (3): 386–96

    Article  PubMed  CAS  Google Scholar 

  162. Wyke S, Tisdale M. NF-κB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle. Br J Cancer 2005; 92 (4): 711–21

    Article  PubMed  CAS  Google Scholar 

  163. Ji LL, Gomez-Cabrera MC, Steinhafel N, et al. Acute exercise activates nuclear factor (NF)-κB signaling pathway in rat skeletal muscle. FASEB J 2004; 18 (13): 1499–506

    Article  PubMed  CAS  Google Scholar 

  164. Ho RC, Hirshman MF, Li Y, et al. Regulation of IκB kinase and NF-κB in contracting adult rat skeletal muscle. Am J Physiol Cell Physiol 2005; 289 (4): C794–801

    Article  PubMed  CAS  Google Scholar 

  165. Durham WJ, Li Y-P, Gerken E, et al. Fatiguing exercise reduces DNA binding activity of NF-κB in skeletal muscle nuclei. J Appl Physiol 2004; 97 (5): 1740–5

    Article  PubMed  CAS  Google Scholar 

  166. Murphy LO, MacKeigan JP, Blenis J. A network of immediate early gene products propagates subtle differences in mitogen activated protein kinase signal amplitude and duration. Mol Cell Biol 2004; 24 (1): 144–53

    Article  PubMed  CAS  Google Scholar 

  167. Simone C, Forcales CS, Hill DA, et al. Pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci. Nat Genet 2004; 36 (7): 738–42

    Article  PubMed  CAS  Google Scholar 

  168. Zhao M, New L, Kravchenko VV, et al. Regulation of the MEF2 family of transcription factors by p38. Mol Cell Biol 1999; 19 (1): 21–30

    PubMed  CAS  Google Scholar 

  169. Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2004; 117 (3): 399–412

    Article  PubMed  CAS  Google Scholar 

  170. Flück M, Hoppeler H. Molecular basis of skeletal muscle plasticity from gene to form and function. Rev Physiol Biochem Pharmacol 2003; 146: 159–216

    Article  PubMed  CAS  Google Scholar 

  171. Hawley JA. Adaptations of skeletal muscle to prolonged, intense endurance training. Clin Exp Pharmacol Physiol 2002; 29: 218–22

    Article  PubMed  CAS  Google Scholar 

  172. Adhihetty PJ, Irrcher I, Joseph AM, et al. Plasticity of skeletal muscle mitochondria in response to contractile activity. Exp Physiol 2003; 88 (1): 99–107

    Article  PubMed  CAS  Google Scholar 

  173. Hoppeler H, Flück M. Plasticity of skeletal muscle mitochondria: structure and function. Med Sci Sports Exerc 2003; 35 (1): 95–104

    Article  PubMed  CAS  Google Scholar 

  174. Goffart S, Wiesner RJ. Regulation and co-ordination of nuclear gene expression during mitochondrial biogenesis. Exp Physiol 2003; 88 (1): 33–40

    Article  PubMed  CAS  Google Scholar 

  175. Hood DA, Irrcher I, Ljubicic V, et al. Coordination of metabolic plasticity in skeletal muscle. J Exp Biol 2006; 209 (12): 2265–75

    Article  PubMed  CAS  Google Scholar 

  176. Freyssenet D, Irrcher I, Connor MK, et al. Calcium-regulated changes in the mitochondrial phenotype in skeletal muscle cells. Am J Physiol Cell Physiol 2004; 286: C1053-61

    Article  PubMed  CAS  Google Scholar 

  177. Gleyzer N, Vercauteren K, Scarpulla RC. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol 2005; 25 (4): 1354–66

    Article  PubMed  CAS  Google Scholar 

  178. Scarpulla RC. Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene 2002; 286 (1): 81–9

    Article  PubMed  CAS  Google Scholar 

  179. Irrcher I, Hood DA. Regulation of Egr-1, SRF, and Sp1 mRNA expression in contracting skeletal muscle cells. J Appl Physiol 2004; 97 (6): 2207–13

    Article  PubMed  CAS  Google Scholar 

  180. Connor MK, Irrcher I, Hood DA. Contractile activity-induced transcriptional activation of cytochrome c involves Sp1 and is proportional to mitochondrial ATP synthesis in C2C12 muscle cells. J Biol Chem 2001; 276 (19): 15898–904

    Article  PubMed  CAS  Google Scholar 

  181. Short KR, Vittone JL, Bigelow ML, et al. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes 2003; 52 (8): 1888–96

    Article  PubMed  CAS  Google Scholar 

  182. Baar K, Wende AR, Jones TE, et al. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J 2002; 16 (14): 1879–86

    Article  PubMed  CAS  Google Scholar 

  183. Scarpulla RC. Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 2006; 97 (4): 673–83

    Article  PubMed  CAS  Google Scholar 

  184. Lin J, Wu H, Tarr PT, et al. Transcriptional co-activator PG-C-1[α] drives the formation of slow-twitch muscle fibres. Nature 2002; 418 (6899): 797–801

    Article  PubMed  CAS  Google Scholar 

  185. Santel A, Fuller M. Control of mitochondrial morphology by a human mitofusin. J Cell Sci 2001; 114 (5): 867–74

    PubMed  CAS  Google Scholar 

  186. Santel A, Frank S, Gaume B, et al. Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci 2003; 116 (13): 2763–74

    Article  PubMed  CAS  Google Scholar 

  187. Bach D, Pich S, Soriano FX, et al. Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. J Biol Chem 2003; 278 (19): 17190–7

    Article  PubMed  CAS  Google Scholar 

  188. Cartoni R, Leger B, Hock MB, et al. Mitofusins 1/2 and ERRa expression are increased in human skeletal muscle after physical exercise. J Physiol 2005; 567 (1): 349–58

    Article  PubMed  CAS  Google Scholar 

  189. Soriano FX, Liesa M, Bach D, et al. Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator activated receptor-γ coactivator-1α, estrogen-related receptor α, and mitofusin 2. Diabetes 2006; 55 (6): 1783–91

    Article  PubMed  CAS  Google Scholar 

  190. Kanki T, Ohgaki K, Gaspari M, et al. Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA. Mol Cell Biol 2004; 24 (22): 9823–34

    Article  PubMed  CAS  Google Scholar 

  191. Maniura-Weber K, Goffart S, Garstka HL, et al. Transient overexpression of mitochondrial transcription factor A (TFAM) is sufficient to stimulate mitochondrial DNA transcription, but not sufficient to increase mtDNA copy number in cultured cells. Nucl Acid Res 2004; 32 (20): 6015–27

    Article  CAS  Google Scholar 

  192. Wu Z, Puigserver P, Andersson U, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 1999; 98 (1): 115–24

    Article  PubMed  CAS  Google Scholar 

  193. Gordon JW, Rungi AA, Inagaki H, et al. Plasticity in skeletal, cardiac and smooth muscle selected contribution: effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle. J Appl Physiol 2001; 90: 389–96

    Article  PubMed  CAS  Google Scholar 

  194. Bengtsson J, Gustafsson T, Widegren U, et al. Mitochondrial transcription factor A and respiratory complex IV increase in response to exercise training in humans. Pflugers Arch 2001; 443 (1): 61–6

    Article  PubMed  CAS  Google Scholar 

  195. Vega RB, Huss JM, Kelly DP. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor a in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 2000; 20 (5): 1868–76

    Article  PubMed  CAS  Google Scholar 

  196. Oberkofler H, Esterbauer H, Linnemayr V, et al. Peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 recruitment regulates PPAR subtype specificity. J Biol Chem 2002; 277 (19): 16750–7

    Article  PubMed  CAS  Google Scholar 

  197. Finck BN, Kelly DP. PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 2006; 116 (3): 615–22

    Article  PubMed  CAS  Google Scholar 

  198. Lee C-H, Olson P, Evans RM. Lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors (minireview). Endocrinology 2003; 144 (6): 2201–7

    Article  PubMed  CAS  Google Scholar 

  199. Luquet S, Lopez-Soriano J, Holst D, et al. Peroxisome proliferator-activated receptor-δ controls muscle development and oxidative capability. FASEB J 2003; 17 (15): 2299–301

    PubMed  CAS  Google Scholar 

  200. Wang Y, Zhang C, Yu RT, et al. Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol 2004; 2 (10): e294

    Article  PubMed  CAS  Google Scholar 

  201. Russell AP, Hesselink MKC, Lo SK, et al. Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. FASEB J 2005; 19 (8): 986–8

    PubMed  CAS  Google Scholar 

  202. Fritz T, Kramer DK, Karlsson HK, et al. Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients. Diabetes Metab Res Rev 2006; 22 (6): 492–8

    Article  PubMed  CAS  Google Scholar 

  203. Coffey VG, Shield A, Canny BJ, et al. Interaction of contractile activity and training history on mRNA abundance in skeletal muscle from trained athletes. Am J Physiol Endocrinol Metab 2006; 290 (5): E849–55

    Article  PubMed  CAS  Google Scholar 

  204. Norrbom J, Sundberg CJ, Ameln H, et al. PGC-1a mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle. J Appl Physiol 2003; 96 (1): 189–94

    Article  PubMed  Google Scholar 

  205. Pilegaard H, Saltin B, Neufer PD. Exercise induces transient transcriptional activation of the PGC-1α gene in human skeletal muscle. J Physiol 2003; 546 (3): 851–8

    Article  PubMed  CAS  Google Scholar 

  206. Tunstall RJ, Mehan KA, Wadley GD, et al. Exercise training increases lipid metabolism gene expression in human skeletal muscle. Am J Physiol Endocrinol Metab 2002; 283: E66–72

    PubMed  CAS  Google Scholar 

  207. Pilegaard H, Osada T, Andersen LT, et al. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. Metabolism 2005; 54 (8): 1048–55

    Article  PubMed  CAS  Google Scholar 

  208. Hildebrandt AL, Pilegaard H, Neufer PD. Differential transcriptional activation of select metabolic genes in response to variations in exercise intensity and duration in red and white skeletal muscle. Am J Physiol Endocrinol Metab 2003; 285 (5): E1021–7

    PubMed  CAS  Google Scholar 

  209. Phillips SM, Tipton KD, Aarsland A, et al. Mixed muscle protein synthesis and breakdown after resistance exercise in humans. Am J Physiol Endocrinol Metab 1997; 36: E99–107

    Google Scholar 

  210. Chesley A, MacDougall JD, Tarnopolsky MA, et al. Changes in human muscle protein synthesis after resistance exercise. J Appl Physiol 1992; 73 (4): 1383–8

    PubMed  CAS  Google Scholar 

  211. Jones SW, Hill RJ, Krasney PA, et al. Disuse atrophy and exercise rehabilitation in humans profoundly affects the expression of genes associated with regulation of skeletal muscle mass. FASEB J 2004; 18 (9): 1025–7

    PubMed  CAS  Google Scholar 

  212. Wang X, Li W, Williams M, et al. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J 2001; 20 (16): 4370–9

    Article  PubMed  CAS  Google Scholar 

  213. Farrell PA, Hernandez JM, Fedele MJ, et al. Eukaryotic initiation factors and protein synthesis after resistance exercise in rats. J Appl Physiol 2000; 88 (3): 1036–42

    PubMed  CAS  Google Scholar 

  214. Hannan KM, Brandenburger Y, Jenkins A, et al. mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol Cell Biol 2003; 23 (23): 8862–77

    Article  PubMed  CAS  Google Scholar 

  215. Musaro A, McCullagh K, Paul A, et al. Localized IGF-1 trans-gene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet 2001; 27 (2): 195–200

    Article  PubMed  CAS  Google Scholar 

  216. Adams GR, McCue SA. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats. J Appl Physiol 1998; 84 (5): 1716–22

    PubMed  CAS  Google Scholar 

  217. Song YH, Godard M, Li Y, et al. Insulin-like growth factor I-mediated skeletal muscle hypertrophy is characterized by increased mTOR-p70S6K signaling without increased Akt phosphorylation. J Investig Med 2005; 53 (3): 135–42

    Article  PubMed  CAS  Google Scholar 

  218. Shen W-H, Boyle DW, Wisniowski P, et al. Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids. J Endocrinol 2005; 185 (2): 275–89

    Article  PubMed  CAS  Google Scholar 

  219. Vary TC. IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis. Am J Physiol Regul Integr Comp Physiol 2006; 290 (2): R313–21

    Article  PubMed  CAS  Google Scholar 

  220. Chakravarthy MV, Abraha TW, Schwartz RJ, et al. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3’-kinase/Akt signaling pathway. J Biol Chem 2000; 275 (46): 35942–52

    Article  PubMed  CAS  Google Scholar 

  221. Jacquemin V, Furling D, Bigot A, et al. IGF-1 induces human myotube hypertrophy by increasing cell recruitment. Exp Cell Res 2004; 299 (1): 148–58

    Article  PubMed  CAS  Google Scholar 

  222. Adams GR, Haddad F, Baldwin KM. Time course of changes in markers of myogenesis in overloaded rat skeletal muscles. J Appl Physiol 1999; 87 (5): 1705–12

    PubMed  CAS  Google Scholar 

  223. Adams GR, Cheng DC, Haddad F, et al. Skeletal muscle hypertrophy in response to isometric, lengthening, and shortening training bouts of equivalent duration. J Appl Physiol 2004; 96: 1613–8

    Article  PubMed  CAS  Google Scholar 

  224. Hameed M, Orrell RW, Cobbold M, et al. Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance training. J Physiol 2003; 547 (1): 247–54

    Article  PubMed  CAS  Google Scholar 

  225. Kim J-S, Cross JM, Bamman MM. Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women. Am J Physiol Endocrinol Metab 2005; 288 (6): E1110–19

    Article  PubMed  CAS  Google Scholar 

  226. Spangenburg EE, Abraha T, Childs TE, et al. Skeletal muscle IGF-binding protein-3 and-5 expressions are age, muscle and load dependent. Am J Physiol Endocrinol Metab 2002; 284: E340–50

    PubMed  Google Scholar 

  227. Petrella JK, Kim J-S, Cross JM, et al. Efficacy of myonuclear addition may explain differential myofiber growth among resistance trained young and older men and women. Am J Physiol Endocrinol Metab 2006; 291 (5): E937–46

    Article  PubMed  CAS  Google Scholar 

  228. Bamman MM, Shipp JR, Jiang J, et al. Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab 2001; 280 (3): E383–90

    PubMed  CAS  Google Scholar 

  229. Psilander N, Damsgaard R, Pilegaard H. Resistance exercise alters MRF and IGF-1 mRNA content in human skeletal muscle. J Appl Physiol 2003; 95: 1038–44

    PubMed  CAS  Google Scholar 

  230. Bickel CS, Slade JM, Haddad F, et al. Acute molecular responses of skeletal muscle to resistance exercise in able-bodied and spinal cord-injured subjects. J Appl Physiol 2003; 94 (6): 2255–62

    PubMed  CAS  Google Scholar 

  231. Kostek MC, Delmonico MJ, Reichel JB, et al. Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults. J Appl Physiol 2005; 98 (6): 2147–54

    Article  PubMed  CAS  Google Scholar 

  232. Pherson P, Dennis R, Faulkner J. Sarcomere dynamics and contraction-induced injury to maximally activated single muscle fibres from soleus muscles of rats. J Physiol 1997; 500: 523–80

    Google Scholar 

  233. McCully KK, Faulkner JA. Injury to skeletal muscle fibers of mice following lengthening contractions. J Appl Physiol 1985; 59 (1): 119–26

    PubMed  CAS  Google Scholar 

  234. Zammit PS, Golding JP, Nagata Y, et al. Muscle satellite cells adopt divergent fates: a mechanism for self-renewal? J Cell Biol 2004; 166 (3): 347–57

    Article  PubMed  CAS  Google Scholar 

  235. Li P, Akimoto T, Zhang M, et al. Resident stem cells are not required for exercise-induced fiber-type switching and angiogenesis but are necessary for activity-dependent muscle growth. Am J Physiol Cell Physiol 2006; 290 (6): C1461–8

    Article  PubMed  CAS  Google Scholar 

  236. Ishido M, Kami K, Masuhara M. Localization of MyoD, myogenin and cell cycle regulatory factors in hypertrophying skeletal muscle. Acta Physiol Scand 2004; 180: 281–9

    Article  PubMed  CAS  Google Scholar 

  237. Haddad F, Adams GR. Exercise effects on muscle insulin signaling and action: selected contribution: acute cellular and molecular responses to resistance exercise. J Appl Physiol 2002; 93 (1): 394–403

    PubMed  CAS  Google Scholar 

  238. Vissing K, Andersen JL, Harridge SDR, et al. Gene expression of myogenic factors and phenotype-specific markers in electrically stimulated muscle of paraplegics. J Appl Physiol 2005; 99 (1): 164–72

    Article  PubMed  CAS  Google Scholar 

  239. Kosek DJ, Kim J-S, Petrella JK, et al. Efficacy of 3 D/WK resistance training on myofiber hypertrophy and myogenic mechanisms in young versus older adults. J Appl Physiol 2006; 101 (2): 531–44

    Article  PubMed  CAS  Google Scholar 

  240. Siu PM, Donley DA, Bryner RW, et al. Myogenin and oxidative enzyme gene expression levels are elevated in rat soleus muscles after endurance training. J Appl Physiol 2004; 97 (1): 277–85

    PubMed  CAS  Google Scholar 

  241. Kadi F, Johansson F, Johansson R, et al. Effects of one bout of endurance exercise on the expression of myogenin in human quadriceps muscle. Histochem Cell Biol 2004; 121: 329–34

    Article  PubMed  CAS  Google Scholar 

  242. Reid MB. Response of the ubiquitin-proteasome pathway to changes in muscle activity. Am J Physiol Regul Integr Comp Physiol 2005; 288 (6): R1423–31

    Article  PubMed  CAS  Google Scholar 

  243. Du J, Wang X, Miereles C, et al. Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 2004; 113 (1): 115–23

    PubMed  CAS  Google Scholar 

  244. Tischler ME, Rosenberg S, Satarug S, et al. Different mechanisms of increased proteolysis in atrophy induced by denervation or unweighting of rat soleus muscle. Metabolism 1990; 39 (7): 756–63

    Article  PubMed  CAS  Google Scholar 

  245. Lecker SH, Jagoe RT, Gilbert A, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 2004; 18 (1): 39–51

    Article  PubMed  CAS  Google Scholar 

  246. Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001; 294 (5547): 1704–8

    Article  PubMed  CAS  Google Scholar 

  247. Kandarian S, Jackman R. Intracellular signaling during skeletal muscle atrophy. Muscle Nerve 2006; 33 (2): 155–65

    Article  PubMed  CAS  Google Scholar 

  248. Tintignac LA, Lagirand J, Batonnet S, et al. Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. J Biol Chem 2005; 280 (4): 2847–56

    Article  PubMed  CAS  Google Scholar 

  249. Gomes MD, Lecker SH, Jagoe RT, et al. Atrogin-1, a muscle specific F-box protein highly expressed during muscle atrophy. PNAS 2001; 98 (25): 14440–5

    Article  PubMed  CAS  Google Scholar 

  250. Wagner KR, Liu X, Chang X, et al. Muscle regeneration in the prolonged absence of myostatin. PNAS 2005; 102 (7): 2519–24

    Article  PubMed  CAS  Google Scholar 

  251. McNally EM. Powerful genes: myostatin regulation of human muscle mass. N Engl J Med 2004; 350 (26): 2642–4

    Article  PubMed  CAS  Google Scholar 

  252. Schuelke M, Wagner KR, Stolz LE, et al. Myostatin mutation associated with gross hypertrophy in a child. N Engl J Med 2004; 350: 2682–8

    Article  PubMed  CAS  Google Scholar 

  253. McPherron AC, Lee S-J. Double muscling in cattle due to mutations in the myostatin gene. PNAS 1997; 94 (23): 12457–61

    Article  PubMed  CAS  Google Scholar 

  254. Reisz-Porszasz S, Bhasin S, Artaza JN, et al. Lower skeletal muscle mass in male transgenic mice with muscle-specific over expression of myostatin. Am J Physiol Endocrinol Metab 2003; 285: E876–88

    PubMed  CAS  Google Scholar 

  255. Langley B, Thomas M, Bishop A, et al. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem 2002; 277 (51): 49831–40

    Article  PubMed  CAS  Google Scholar 

  256. McCroskery S, Thomas M, Maxwell L, et al. Myostatin negatively regulates satellite cell activation and self-renewal. J Cell Biol 2003; 162 (6): 1135–47

    Article  PubMed  CAS  Google Scholar 

  257. Lee S-J, McPherron AC. Regulation of myostatin activity and muscle growth. PNAS 2001; 98 (16): 9306–11

    Article  PubMed  CAS  Google Scholar 

  258. Sandri M, Podhorska-Okolow M, Geromel V, et al. Exercise induces myonuclear ubiquitination and apoptosis in dystrophin-deficient muscle of mice. J Neuropathol Exp Neurol 1997; 56 (1): 45–57

    Article  PubMed  CAS  Google Scholar 

  259. Stupka N, Tarnopolsky MA, Yardley NJ, et al. Cellular adaptation to repeated eccentric exercise-induced muscle damage. J Appl Physiol 2001; 91 (4): 1669–78

    PubMed  CAS  Google Scholar 

  260. Willoughby DS, Taylor M, Taylor L. Glucocorticoid receptor and ubiquitin expression after repeated eccentric exercise. Med Sci Sports Exerc 2003; 35 (12): 2023-31

    Article  PubMed  CAS  Google Scholar 

  261. Yang Y, Jemiolo B, Trappe SW. Proteolytic mRNA expression in response to acute resistance exercise in human single skeletal muscle fibers. J Appl Physiol 2006; 101 (5): 1442–50

    Article  PubMed  CAS  Google Scholar 

  262. Dupont-Versteegden EE, Fluckey JD, Knox M, et al. Effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats. J Appl Physiol 2006; 101 (1): 202–12

    Article  PubMed  CAS  Google Scholar 

  263. Roth SM, Martel GF, Ferrell RE, et al. Myostatin gene expression is reduced in humans with heavy-resistance strength training. Exp Biol Med 2003; 228: 706–9

    CAS  Google Scholar 

  264. Raue U, Slivka D, Jemiolo B, et al. Myogenic gene expression at rest and after a bout of resistance exercise in young (18–30 yr) and old (80–89 yr) women. J Appl Physiol 2006; 101 (1): 53–9

    Article  PubMed  CAS  Google Scholar 

  265. Willoughby DS. Effects of heavy resistance training on myostatin mRNA and protein expression. Med Sci Sports Exerc 2004; 36 (4): 574–82

    Article  PubMed  Google Scholar 

  266. Matsakas A, Friedel A, Hertrampf T, et al. Short-term endurance training results in a muscle-specific decrease of myostatin mRNA content in the rat. Acta Physiol Scand 2005; 183 (3): 299–307

    Article  PubMed  CAS  Google Scholar 

  267. Leveritt MD, Abernethy PJ, Barry BK, et al. Concurrent strength and endurance training: a review. Sports Med 1999; 28 (6): 413–27

    Article  PubMed  CAS  Google Scholar 

  268. Hickson RC. Interference of strength development by simultaneously training for strength and endurance. Eur J Appl Physiol Occup Physiol 1980; 45: 255–63

    Article  PubMed  CAS  Google Scholar 

  269. Hood DA. Plasticity in skeletal, cardiac, and smooth muscle invited review: contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 2001; 90: 1137–57

    PubMed  CAS  Google Scholar 

  270. Riedy M, Moore RL, Gollnick PD. Adaptive response of hypertrophied skeletalmuscle to endurance training. J Appl Physiol 1985; 59 (1): 127–31

    PubMed  CAS  Google Scholar 

  271. Stone J, Brannon T, Haddad F, et al. Adaptive responses of hypertrophying skeletal muscle to endurance training. J Appl Physiol 1996; 81 (2): 665–72

    PubMed  CAS  Google Scholar 

  272. Putman C, Xu X, Gillies E, et al. Effects of strength, endurance and combined training on myosin heavy chain content and fibre-type distribution in humans. Eur J Appl Physiol 2004; 92 (4–5): 376–84

    PubMed  CAS  Google Scholar 

  273. Browne GJ, Proud CG. Regulation of peptide-chain elongation in mammalian cells. Eur J Biochem 2002; 269 (22): 5360–8

    Article  PubMed  CAS  Google Scholar 

  274. Ryazanov AG. Ca2+/calmodulin-dependent phosphorylation of elongation factor 2. FEBS Lett 1987; 214 (2): 331–4

    Article  PubMed  CAS  Google Scholar 

  275. Horman S, Browne GJ, Krause U, et al. Activation of AMP activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 2002; 12 (16): 1419–23

    Article  PubMed  CAS  Google Scholar 

  276. Rose AJ, Broholm C, Kiillerich K, et al. Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men. J Physiol (Lond) 2005; 569 (1): 223–8

    Article  CAS  Google Scholar 

  277. Browne GJ, Proud CG. A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol Cell Biol 2004; 24 (7): 2986–97

    Article  PubMed  CAS  Google Scholar 

  278. Daitoku H, Yamagata K, Matsuzaki H, et al. Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. Diabetes 2003; 52 (3): 642–9

    Article  PubMed  CAS  Google Scholar 

  279. Matsuzaki H, Daitoku H, Hatta M, et al. Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. PNAS 2003; 100 (20): 11285–90

    Article  PubMed  CAS  Google Scholar 

  280. Southgate RJ, Bruce CR, Carey AL, et al. PGC-1a gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FoxO1 in insulin-stimulated skeletal muscle. FASEB J 2005; 19 (14): 2072–4

    PubMed  CAS  Google Scholar 

  281. Hoffman EP, Nader GA. Balancing muscle hypertrophy and atrophy. Nat Med 2004; 10 (6): 584–5

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Work from our laboratory on training adaptation was supported by research grants from the Australian Sports Commission and the RMIT University VRI II grant scheme. The authors have no conflicts of interest relevant to the contents of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John A. Hawley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coffey, V.G., Hawley, J.A. The Molecular Bases of Training Adaptation. Sports Med 37, 737–763 (2007). https://doi.org/10.2165/00007256-200737090-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00007256-200737090-00001

Keywords

Navigation