European Journal of Applied Physiology

, Volume 111, Issue 3, pp 403–420 | Cite as

Disuse of the musculo-skeletal system in space and on earth

  • M. V. NariciEmail author
  • M. D. de Boer
Original Article


Muscle mass and strength are well known to decline in response to actual and simulated microgravity exposure. However, despite the considerable knowledge gained on the physiological changes induced by spaceflight, the mechanisms of muscle atrophy and the effectiveness of in-flight countermeasures still need to be fully elucidated. The present review examines the effects and mechanisms of actual and simulated microgravity on single fibre and whole muscle structural and functional properties, protein metabolism, tendon mechanical properties, neural drive and reflex excitability. The effects of inflight countermeasures are also discussed in the light of recent advances in resistive loading techniques, in combined physical, pharmacological and nutritional interventions as well as in the development of artificial gravity systems. Emphasis has been given to the pioneering work of Pietro Enrico di Prampero in the development of artificial gravity systems and in the progress of knowledge on the limits of human muscular performance in space.


Skeletal muscle Microgravity Spaceflight Countermeasures Atrophy 



A significant portion of this Review paper makes direct reference to published literature of Prof. PE di Prampero and co-workers and indirectly, to work performed through the close and most enjoyable collaboration we shared over the last 30 years. We are also grateful to the funding agencies that partly supported this work (ESA, ASI and the Slovenian Ministry of Defence) and to Prof. Rado Pisot (University of Primorska, Science and Research Centre Koper, Institute for Kinesiology Research, Slovenia) for creating the opportunity for performing some of the ground-based studies cited in this paper.


  1. Adams GR, Hather BM, Dudley GA (1994) Effect of short-term unweighting on human skeletal muscle strength and size. Aviat Space Environ Med 65:1116–1121PubMedGoogle Scholar
  2. Akima H, Kawakami Y, Kubo K, Sekiguchi C, Ohshima H, Miyamoto A, Fukunaga T (2000) Effect of short-duration spaceflight on thigh and leg muscle volume. Med Sci Sports Exerc 32:1743–1747PubMedCrossRefGoogle Scholar
  3. Akima H, Kubo K, Imai M, Kanehisa H, Suzuki Y, Gunji A, Fukunaga T (2001) Inactivity and muscle: effect of resistance training during bed rest on muscle size in the lower limb. Acta Physiol Scand 172:269–278PubMedCrossRefGoogle Scholar
  4. Akima H, Katayama K, Sato K, Ishida K, Masuda K, Takada H, Watanabe Y, Iwase S (2005) Intensive cycle training with artificial gravity maintains muscle size during bed rest. Aviat Space Environ Med 76:923–929PubMedGoogle Scholar
  5. Alkner BA, Tesch PA (2004a) Efficacy of a gravity-independent resistance exercise device as a countermeasure to muscle atrophy during 29-day bed rest. Acta Physiol Scand 181:345–357PubMedCrossRefGoogle Scholar
  6. Alkner BA, Tesch PA (2004b) Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise. Eur J Appl Physiol 93:294–305PubMedCrossRefGoogle Scholar
  7. Andersen JL, Mohr T, Biering-Sorensen F, Galbo H, Kjaer M (1996) Myosin heavy chain isoform transformation in single fibres from m. vastus lateralis in spinal cord injured individuals: effects of long-term functional electrical stimulation (FES). Pflugers Arch 431:513–518PubMedCrossRefGoogle Scholar
  8. Antonutto G, Capelli C, Di Prampero PE (1991) Pedalling in space as a countermeasure to microgravity deconditioning. Microgravity Q 1:93–101Google Scholar
  9. Antonutto G, Capelli C, Girardis M, Zamparo P, di Prampero PE (1999) Effects of microgravity on maximal power of lower limbs during very short efforts in humans. J Appl Physiol 86:85–92PubMedGoogle Scholar
  10. Apseloff G, Girten B, Walker M, Shepard DR, Krecic ME, Stern LS, Gerber N (1993) Aminohydroxybutane bisphosphonate and clenbuterol prevent bone changes and retard muscle atrophy respectively in tail-suspended rats. J Pharmacol Exp Ther 264:1071–1078PubMedGoogle Scholar
  11. Baldwin KM, Haddad F (2001) Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. J Appl Physiol 90:345–357PubMedCrossRefGoogle Scholar
  12. Bamman MM, Clarke MS, Feeback DL, Talmadge RJ, Stevens BR, Lieberman SA, Greenisen MC (1998) Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution. J Appl Physiol 84:157–163PubMedGoogle Scholar
  13. Belavy DL, Miokovic T, Armbrecht G, Richardson CA, Rittweger J, Felsenberg D (2009) Differential atrophy of the lower-limb musculature during prolonged bed-rest. Eur J Appl Physiol 107:489–499PubMedCrossRefGoogle Scholar
  14. Berg HE, Tesch PA (1996) Changes in muscle function in response to 10 days of lower limb unloading in humans. Acta Physiol Scand 157:63–70PubMedCrossRefGoogle Scholar
  15. Berg HE, Tesch PA (1998) Force and power characteristics of a resistive exercise device for use in space. Acta Astronaut 42:219–230Google Scholar
  16. Berg HE, Dudley GA, Haggmark T, Ohlsen H, Tesch PA (1991) Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol 70:1882–1885PubMedCrossRefGoogle Scholar
  17. Berg HE, Dudley GA, Hather B, Tesch PA (1993) Work capacity and metabolic and morphologic characteristics of the human quadriceps muscle in response to unloading. Clin Physiol 13:337–347PubMedCrossRefGoogle Scholar
  18. Berg HE, Larsson L, Tesch PA (1997) Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol 82:182–188PubMedCrossRefGoogle Scholar
  19. Berg HE, Eiken O, Miklavcic L, Mekjavic IB (2007) Hip, thigh and calf muscle atrophy and bone loss after 5-week bedrest inactivity. Eur J Appl Physiol 99:283–289PubMedCrossRefGoogle Scholar
  20. Boudreau NJ, Jones PL (1999) Extracellular matrix and integrin signalling: the shape of things to come. Biochem J 339(Pt 3):481–488PubMedCrossRefGoogle Scholar
  21. Brooks N, Cloutier GJ, Cadena SM, Layne JE, Nelsen CA, Freed AM, Roubenoff R, Castaneda-Sceppa C (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 105:241–248PubMedCrossRefGoogle Scholar
  22. Caiozzo VJ, Baker MJ, Herrick RE, Tao M, Baldwin KM (1994) Effect of spaceflight on skeletal muscle: mechanical properties and myosin isoform content of a slow muscle. J Appl Physiol 76:1764–1773PubMedCrossRefGoogle Scholar
  23. Caiozzo VJ, Haddad F, Baker MJ, Herrick RE, Prietto N, Baldwin KM (1996) Microgravity-induced transformations of myosin isoforms and contractile properties of skeletal muscle. J Appl Physiol 81:123–132PubMedGoogle Scholar
  24. Caiozzo VJ, Haddad F, Lee S, Baker M, Paloski W, Baldwin KM (2009) Artificial gravity as a countermeasure to microgravity: a pilot study examining the effects on knee extensor and plantar flexor muscle groups. J Appl Physiol 107:39–46PubMedCrossRefGoogle Scholar
  25. Caruso J, Hamill J, Yamauchi M, Mercado D, Cook T, Higginson B, O’Meara S, Elias J, Siconolfi S (2005) Albuterol aids resistance exercise in reducing unloading-induced ankle extensor strength losses. J Appl Physiol 98:1705–1711PubMedCrossRefGoogle Scholar
  26. Chase GA, Grave C, Rowell LB (1966) Independence of changes in functional and performance capacities attending prolonged bed rest. Aerosp Med 37:1232–1238PubMedGoogle Scholar
  27. Cherepakhin MA, Pervushin VI (1970) Space flight effect on the neuromuscular system of cosmonauts. Kosm Biol Aviakosm Med 4:46–49Google Scholar
  28. Clark BC, Fernhall B, Ploutz-Snyder LL (2006) Adaptations in human neuromuscular function following prolonged unweighting: I. Skeletal muscle contractile properties and applied ischemia efficacy. J Appl Physiol 101:256–263PubMedCrossRefGoogle Scholar
  29. Clark BC, Pierce JR, Manini TM, Ploutz-Snyder LL (2007) Effect of prolonged unweighting of human skeletal muscle on neuromotor force control. Eur J Appl Physiol 100:53–62PubMedCrossRefGoogle Scholar
  30. Convertino VA (1990) Physiological adaptations to weightlessness: effects on exercise and work performance. Exerc Sport Sci Rev 18:119–166PubMedCrossRefGoogle Scholar
  31. Convertino VA, Doerr DF, Stein SL (1989) Changes in size and compliance of the calf after 30 days of simulated microgravity. J Appl Physiol 66:1509–1512PubMedGoogle Scholar
  32. Criswell DS, Booth FW, DeMayo F, Schwartz RJ, Gordon SE, Fiorotto ML (1998) Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy. Am J Physiol 275:E373–E379PubMedGoogle Scholar
  33. D’Antona G, Pellegrino MA, Adami R, Rossi R, Carlizzi CN, Canepari M, Saltin B, Bottinelli R (2003) The effect of ageing and immobilization on structure and function of human skeletal muscle fibres. J Physiol 552:499–511PubMedCrossRefGoogle Scholar
  34. Danielsen CC, Andreassen TT (1988) Mechanical properties of rat tail tendon in relation to proximal-distal sampling position and age. J Biomech 21:207–212PubMedCrossRefGoogle Scholar
  35. Davies CT, Rutherford IC, Thomas DO (1987) Electrically evoked contractions of the triceps surae during and following 21 days of voluntary leg immobilization. Eur J Appl Physiol Occup Physiol 56:306–312PubMedCrossRefGoogle Scholar
  36. de Boer MD, Maganaris CN, Seynnes OR, Rennie MJ, Narici MV (2007a) Time course of muscular, neural and tendinous adaptations to 23 day unilateral lower-limb suspension in young men. J Physiol 583:1079–1091PubMedCrossRefGoogle Scholar
  37. de Boer MD, Selby A, Atherton P, Smith K, Seynnes OR, Maganaris CN, Maffulli N, Movin T, Narici MV, Rennie MJ (2007b) The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse. J Physiol 585:241–251PubMedCrossRefGoogle Scholar
  38. de Boer MD, Seynnes OR, di Prampero PE, Pisot R, Mekjavic IB, Biolo G, Narici MV (2008) Effect of 5 weeks horizontal bed rest on human muscle thickness and architecture of weight bearing and non-weight bearing muscles. Eur J Appl Physiol 104:401–407PubMedCrossRefGoogle Scholar
  39. Deschenes MR, Giles JA, McCoy RW, Volek JS, Gomez AL, Kraemer WJ (2002) Neural factors account for strength decrements observed after short-term muscle unloading. Am J Physiol 282:R578–R583Google Scholar
  40. Desplanches D, Hoppeler H, Mayet MH, Denis C, Claassen H, Ferretti G (1998) Effects of bedrest on deltoideus muscle morphology and enzymes. Acta Physiol Scand 162:135–140PubMedCrossRefGoogle Scholar
  41. di Prampero PE (2000) Cycling on Earth, in space, on the Moon. Eur J Appl Physiol 82:345–360PubMedCrossRefGoogle Scholar
  42. di Prampero PE, Antonutto G (1997) Cycling in space to simulate gravity. Int J Sports Med 18(Suppl 4):S324–S326PubMedCrossRefGoogle Scholar
  43. di Prampero PE, Narici MV (2003) Muscles in microgravity: from fibres to human motion. J Biomech 36:403–412PubMedCrossRefGoogle Scholar
  44. di Prampero P, Lazzer S, Antonutto G (2009) Human power centrifuges on the Moon and Mars. Microgravity Sci Technol 21:209–215CrossRefGoogle Scholar
  45. Duchateau J (1995) Bed rest induces neural and contractile adaptations in triceps surae. Med Sci Sports Exerc 27:1581–1589PubMedGoogle Scholar
  46. Duchateau J, Hainaut K (1987) Electrical and mechanical changes in immobilized human muscle. J Appl Physiol 62:2168–2173PubMedGoogle Scholar
  47. Dudley GA, Duvoisin MR, Convertino VA, Buchanan P (1989) Alterations of the in vivo torque-velocity relationship of human skeletal muscle following 30 days exposure to simulated microgravity. Aviat Space Environ Med 60:659–663PubMedGoogle Scholar
  48. Dudley GA, Duvoisin MR, Adams GR, Meyer RA, Belew AH, Buchanan P (1992) Adaptations to unilateral lower limb suspension in humans. Aviat Space Environ Med 63:678–683PubMedGoogle Scholar
  49. Duvoisin MR, Convertino VA, Buchanan P, Gollnick PD, Dudley GA (1989) Characteristics and preliminary observations of the influence of electromyostimulation on the size and function of human skeletal muscle during 30 days of simulated microgravity. Aviat Space Environ Med 60:671–678PubMedGoogle Scholar
  50. Edgerton VR, Roy RR (1994) Neuromuscular adaptation to actual and simulated weightlessness. Adv Space Biol Med 4:33–67PubMedCrossRefGoogle Scholar
  51. Edgerton VR, Zhou MY, Ohira Y, Klitgaard H, Jiang B, Bell G, Harris B, Saltin B, Gollnick PD, Roy RR et al (1995) Human fiber size and enzymatic properties after 5 and 11 days of spaceflight. J Appl Physiol 78:1733–1739PubMedGoogle Scholar
  52. Edgerton VR, McCall GE, Hodgson JA, Gotto J, Goulet C, Fleischmann K, Roy RR (2001) Sensorimotor adaptations to microgravity in humans. J Exp Biol 204:3217–3224PubMedGoogle Scholar
  53. Edman KA (1979) The velocity of unloaded shortening and its relation to sarcomere length and isometric force in vertebrate muscle fibres. J Physiol 291:143–159PubMedGoogle Scholar
  54. Ferrando AA, Stuart CA, Brunder DG, Hillman GR (1995) Magnetic resonance imaging quantitation of changes in muscle volume during 7 days of strict bed rest. Aviat Space Environ Med 66:976–981PubMedGoogle Scholar
  55. Ferrando AA, Lane HW, Stuart CA, Davis-Street J, Wolfe RR (1996) Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol 270:E627–E633PubMedGoogle Scholar
  56. Ferrando AA, Tipton KD, Bamman MM, Wolfe RR (1997) Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J Appl Physiol 82:807–810PubMedGoogle Scholar
  57. Ferrando AA, Tipton KD, Doyle D, Phillips SM, Cortiella J, Wolfe RR (1998) Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. Am J Physiol 275:E864–E871PubMedGoogle Scholar
  58. Ferrando AA, Paddon-Jones D, Wolfe RR (2002) Alterations in protein metabolism during space flight and inactivity. Nutrition 18:837–841PubMedCrossRefGoogle Scholar
  59. Ferretti G, Berg HE, Minetti AE, Moia C, Rampichini S, Narici MV (2001) Maximal instantaneous muscular power after prolonged bed rest in humans. J Appl Physiol 90:431–435PubMedGoogle Scholar
  60. Ferrucci L, Guralnik JM (2003) Inflammation, hormones, and body composition at a crossroad. Am J Med 115:501–502PubMedCrossRefGoogle Scholar
  61. Fitts RH, Riley DR, Widrick JJ (2000) Physiology of a microgravity environment invited review: microgravity and skeletal muscle. J Appl Physiol 89:823–839PubMedGoogle Scholar
  62. Fitts RH, Riley DR, Widrick JJ (2001) Functional and structural adaptations of skeletal muscle to microgravity. J Exp Biol 204:3201–3208PubMedGoogle Scholar
  63. Fitts RH, Romatowski JG, Peters JR, Paddon-Jones D, Wolfe RR, Ferrando AA (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–C320PubMedCrossRefGoogle Scholar
  64. Fluck M, Carson JA, Gordon SE, Ziemiecki A, Booth FW (1999) Focal adhesion proteins FAK and paxillin increase in hypertrophied skeletal muscle. Am J Physiol 277:C152–C162PubMedGoogle Scholar
  65. Fluckey JD, Dupont-Versteegden EE, Montague DC, Knox M, Tesch P, Peterson CA, Gaddy-Kurten D (2002) A rat resistance exercise regimen attenuates losses of musculoskeletal mass during hindlimb suspension. Acta Physiol Scand 176:293–300PubMedCrossRefGoogle Scholar
  66. Gamrin L, Berg HE, Essen P, Tesch PA, Hultman E, Garlick PJ, McNurlan MA, Wernerman J (1998) The effect of unloading on protein synthesis in human skeletal muscle. Acta Physiol Scand 163:369–377PubMedCrossRefGoogle Scholar
  67. Gans C, Bock WJ (1965) The functional significance of muscle architecture—a theoretical analysis. Ergeb Anat Entwicklungsgesch 38:115–142PubMedGoogle Scholar
  68. Gardetto PR, Schluter JM, Fitts RH (1989) Contractile function of single muscle fibers after hindlimb suspension. J Appl Physiol 66:2739–2749PubMedGoogle Scholar
  69. Gibson JN, Halliday D, Morrison WL, Stoward PJ, Hornsby GA, Watt PW, Murdoch G, Rennie MJ (1987) Decrease in human quadriceps muscle protein turnover consequent upon leg immobilization. Clin Sci (Lond) 72:503–509Google Scholar
  70. Gogia P, Schneider VS, LeBlanc AD, Krebs J, Kasson C, Pientok C (1988) Bed rest effect on extremity muscle torque in healthy men. Arch Phys Med Rehabil 69:1030–1032PubMedGoogle Scholar
  71. Gopalakrishnan R, Genc KO, Rice AJ, Lee SM, Evans HJ, Maender CC, Ilaslan H, Cavanagh PR (2010) Muscle volume, strength, endurance, and exercise loads during 6-month missions in space. Aviat Space Environ Med 81:91–102Google Scholar
  72. Goubel F (1997) Changes in mechanical properties of human muscle as a result of spaceflight. Int J Sports Med 18(Suppl 4):S285–S287PubMedCrossRefGoogle Scholar
  73. Greenisen MC, Edgerton VR (1994) Human capabilities in the space environment. In: Nicogossian AE, Huntoon CL, Pool SL (eds) Space physiology and medicine. Lea & Febiger, Philadelphia, PA, pp 194–210Google Scholar
  74. Greenleaf JE, Bernauer EM, Ertl AC, Trowbridge TS, Wade CE (1989a) Work capacity during 30 days of bed rest with isotonic and isokinetic exercise training. J Appl Physiol 67:1820–1826PubMedGoogle Scholar
  75. Greenleaf JE, Bulbulian R, Bernauer EM, Haskell WL, Moore T (1989b) Exercise-training protocols for astronauts in microgravity. J Appl Physiol 67:2191–2204PubMedGoogle Scholar
  76. Grogor’eva LS, Kozlovskaia IB (1987) Effect of weightlessness and hypokinesia on the velocity-strength properties of human muscles. Kosm Biol Aviakosm Med 21:27–30PubMedGoogle Scholar
  77. Hather BM, Adams GR, Tesch PA, Dudley GA (1992) Skeletal muscle responses to lower limb suspension in humans. J Appl Physiol 72:1493–1498PubMedGoogle Scholar
  78. Haus JM, Carrithers JA, Carroll CC, Tesch PA, Trappe TA (2007) Contractile and connective tissue protein content of human skeletal muscle: effects of 35 and 90 days of simulated microgravity and exercise countermeasures. Am J Physiol 293:R1722–R1727Google Scholar
  79. Hespel P, Op’t Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, Dymarkowski S, Van Hecke P, Richter EA (2001) Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol 536:625–633PubMedCrossRefGoogle Scholar
  80. Hikida RS, Gollnick PD, Dudley GA, Convertino VA, Buchanan P (1989) Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity. Aviat Space Environ Med 60:664–670PubMedGoogle Scholar
  81. Hortobagyi T, Dempsey L, Fraser D, Zheng D, Hamilton G, Lambert J, Dohm L (2000) Changes in muscle strength, muscle fibre size and myofibrillar gene expression after immobilization and retraining in humans. J Physiol 524(Pt 1):293–304PubMedCrossRefGoogle Scholar
  82. Jaweed MM (1994) Muscle structure and function. In: Nicogossian AE, Huntoon CL, Pool SL (eds) Space physiology and medicine. Lea & Febiger, Philadelphia, pp 317–326Google Scholar
  83. Kakurin LI, Cherepakhin MA, Pervushin VI (1971) Effect of brief space flights on the human neuromuscular system. Kosm Biol Aviakosm Med 5:53–56Google Scholar
  84. Kawakami Y, Muraoka Y, Kubo K, Suzuki Y, Fukunaga T (2000) Changes in muscle size and architecture following 20 days of bed rest. J Gravit Physiol 7:53–59PubMedGoogle Scholar
  85. Kawakami Y, Akima H, Kubo K, Muraoka Y, Hasegawa H, Kouzaki M, Imai M, Suzuki Y, Gunji A, Kanehisa H, Fukunaga T (2001) Changes in muscle size, architecture, and neural activation after 20 days of bed rest with and without resistance exercise. Eur J Appl Physiol 84:7–12PubMedCrossRefGoogle Scholar
  86. Klossner S, Durieux AC, Freyssenet D, Flueck M (2009) Mechano-transduction to muscle protein synthesis is modulated by FAK. Eur J Appl Physiol 106:389–398PubMedCrossRefGoogle Scholar
  87. Koryak Y (1995) Contractile properties of the human triceps surae muscle during simulated weightlessness. Eur J Appl Physiol Occup Physiol 70:344–350PubMedCrossRefGoogle Scholar
  88. Koryak Y (1998) Effect of 120 days of bed-rest with and without countermeasures on the mechanical properties of the triceps surae muscle in young women. Eur J Appl Physiol Occup Physiol 78:128–135PubMedCrossRefGoogle Scholar
  89. Koryak Y (1999) The effects of long-term simulated microgravity on neuromuscular performance in men and women. Eur J Appl Physiol Occup Physiol 79:168–175PubMedCrossRefGoogle Scholar
  90. Koryak YU (2001) Electrically evoked and voluntary properties of the human triceps surae muscle: effects of long-term spaceflights. Acta Physiol Pharmacol Bulg 26:21–27PubMedGoogle Scholar
  91. Kozlovskaya IB, Grigoriev AI (2004) Russian system of countermeasures on board of the International Space Station (ISS): the first results. Acta Astronaut 55:233–237PubMedCrossRefGoogle Scholar
  92. Kozlovskaya IB, Kreidich Yu V, Oganov VS, Koserenko OP (1981) Pathophysiology of motor functions in prolonged manned space flights. Acta Astronaut 8:1059–1072PubMedCrossRefGoogle Scholar
  93. Kubo K, Akima H, Kouzaki M, Ito M, Kawakami Y, Kanehisa H, Fukunaga T (2000) Changes in the elastic properties of tendon structures following 20 days bed-rest in humans. Eur J Appl Physiol 83:463–468PubMedCrossRefGoogle Scholar
  94. Kubo K, Akima H, Ushiyama J, Tabata I, Fukuoka H, Kanehisa H, Fukunaga T (2004) Effects of 20 days of bed rest on the viscoelastic properties of tendon structures in lower limb muscles. Br J Sports Med 38:324–330PubMedCrossRefGoogle Scholar
  95. Lalani R, Bhasin S, Byhower F, Tarnuzzer R, Grant M, Shen R, Asa S, Ezzat S, Gonzalez-Cadavid NF (2000) Myostatin and insulin-like growth factor-I and -II expression in the muscle of rats exposed to the microgravity environment of the NeuroLab space shuttle flight. J Endocrinol 167:417–428PubMedCrossRefGoogle Scholar
  96. Lambertz D, Perot C, Kaspranski R, Goubel F (2001) Effects of long-term spaceflight on mechanical properties of muscles in humans. J Appl Physiol 90:179–188PubMedGoogle Scholar
  97. Larsson L, Li X, Berg HE, Frontera WR (1996) Effects of removal of weight-bearing function on contractility and myosin isoform composition in single human skeletal muscle cells. Pflugers Arch 432:320–328PubMedCrossRefGoogle Scholar
  98. Lazzer S, Plaino L, Antonutto G (2010) The energetics of cycling on Earth, Moon and Mars. Eur J Appl Physiol (Epub)Google Scholar
  99. LeBlanc A, Gogia P, Schneider V, Krebs J, Schonfeld E, Evans H (1988) Calf muscle area and strength changes after five weeks of horizontal bed rest. Am J Sports Med 16:624–629PubMedCrossRefGoogle Scholar
  100. LeBlanc AD, Schneider VS, Evans HJ, Pientok C, Rowe R, Spector E (1992) Regional changes in muscle mass following 17 weeks of bed rest. J Appl Physiol 73:2172–2178PubMedGoogle Scholar
  101. LeBlanc A, Rowe R, Schneider V, Evans H, Hedrick T (1995) Regional muscle loss after short duration spaceflight. Aviat Space Environ Med 66:1151–1154PubMedGoogle Scholar
  102. LeBlanc A, Rowe R, Evans H, West S, Shackelford L, Schneider V (1997) Muscle atrophy during long duration bed rest. Int J Sports Med 18(Suppl 4):S283–S285PubMedCrossRefGoogle Scholar
  103. LeBlanc A, Lin C, Shackelford L, Sinitsyn V, Evans H, Belichenko O, Schenkman B, Kozlovskaya I, Oganov V, Bakulin A, Hedrick T, Feeback D (2000) Muscle volume, MRI relaxation times (T2), and body composition after spaceflight. J Appl Physiol 89:2158–2164PubMedGoogle Scholar
  104. Lynch GS, Hinkle RT, Faulkner JA (2001) Force and power output of diaphragm muscle strips from mdx and control mice after clenbuterol treatment. Neuromuscul Disord 11:192–196PubMedCrossRefGoogle Scholar
  105. Maltin CA, Delday MI, Watson JS, Heys SD, Nevison IM, Ritchie IK, Gibson PH (1993) Clenbuterol, a beta-adrenoceptor agonist, increases relative muscle strength in orthopaedic patients. Clin Sci (Lond) 84:651–654Google Scholar
  106. McDonald KS, Fitts RH (1995) Effect of hindlimb unloading on rat soleus fiber force, stiffness, and calcium sensitivity. J Appl Physiol 79:1796–1802PubMedGoogle Scholar
  107. Milesi S, Capelli C, Denoth J, Hutchinson T, Stussi E (2000) Effects of 17 days bedrest on the maximal voluntary isometric torque and neuromuscular activation of the plantar and dorsal flexors of the ankle. Eur J Appl Physiol 82:197–205PubMedCrossRefGoogle Scholar
  108. Montgomery LD (1993) Body volume changes during simulated microgravity. II: comparison of horizontal and head-down bed rest. Aviat Space Environ Med 64:899–904PubMedGoogle Scholar
  109. Murton AJ, Constantin D, Greenhaff PL (2008) The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling and atrophy. Biochim Biophys Acta 1782:730–743PubMedGoogle Scholar
  110. Narici M, Capodaglio P (1998) Changes in muscle size and architecture in disuse atrophy. In: Capodaglio P, Narici M (eds) Muscle atrophy: disuse and disease. Le Collane della Fondazione Salvatore Maugeri, PI-ME Press, Pavia, Italy, pp 55–64Google Scholar
  111. Narici M, Cerretelli P (1998) Changes in human muscle architecture in disuse-atrophy evaluated by ultrasound imaging. J Gravit Physiol 5:P73–P74PubMedGoogle Scholar
  112. Narici M, Kayser B, Barattini P, Cerretelli P (2003) Effects of 17-day spaceflight on electrically evoked torque and cross-sectional area of the human triceps surae. Eur J Appl Physiol 90:275–282Google Scholar
  113. Ohira Y, Jiang B, Roy RR, Oganov V, Ilyina-Kakueva E, Marini JF, Edgerton VR (1992) Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb suspension. J Appl Physiol 73:51S–57SPubMedGoogle Scholar
  114. Ohira Y, Yoshinaga T, Ohara M, Nonaka I, Yoshioka T, Yamashita-Goto K, Shenkman BS, Kozlovskaya IB, Roy RR, Edgerton VR (1999) Myonuclear domain and myosin phenotype in human soleus after bed rest with or without loading. J Appl Physiol 87:1776–1785PubMedGoogle Scholar
  115. Paddon-Jones D, Sheffield-Moore M, Cree MG, Hewlings SJ, Aarsland A, Wolfe RR, Ferrando AA (2006) Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. J Clin Endocrinol Metab 91:4836–4841PubMedCrossRefGoogle Scholar
  116. Pavy-Le Traon A, Heer M, Narici MV, Rittweger J, Vernikos J (2007) From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 101:143–194PubMedCrossRefGoogle Scholar
  117. Payette H, Roubenoff R, Jacques PF, Dinarello CA, Wilson PW, Abad LW, Harris T (2003) Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study. J Am Geriatr Soc 51:1237–1243PubMedCrossRefGoogle Scholar
  118. Ploutz-Snyder LL, Tesch PA, Crittenden DJ, Dudley GA (1995) Effect of unweighting on skeletal muscle use during exercise. J Appl Physiol 79:168–175PubMedGoogle Scholar
  119. Ploutz-Snyder LL, Tesch PA, Hather BM, Dudley GA (1996) Vulnerability to dysfunction and muscle injury after unloading. Arch Phys Med Rehabil 77:773–777PubMedCrossRefGoogle Scholar
  120. Prockop DJ, Kivirikko KI (1995) Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem 64:403–434PubMedCrossRefGoogle Scholar
  121. Rapcsak M, Oganov VS, Szoor A, Skuratova SA, Szilagyi T, Takacs O (1983) Effect of weightlessness on the function of rat skeletal muscles on the biosatellite “Cosmos-1129”. Acta Physiol Hung 62:225–228PubMedGoogle Scholar
  122. Reeves ND, Maganaris CN, Ferretti G, Narici MV (2002) Influence of simulated microgravity on human skeletal muscle architecture and function. J Gravit Physiol 9:P153–P154PubMedGoogle Scholar
  123. Reeves ND, Maganaris CN, Ferretti G, Narici MV (2005) Influence of 90-day simulated microgravity on human tendon mechanical properties and the effect of resistive countermeasures. J Appl Physiol 98:2278–2286PubMedCrossRefGoogle Scholar
  124. Rennie MJ, Selby A, Atherton P, Smith K, Kumar V, Glover EL, Philips SM (2010) Facts, noise and wishful thinking: muscle protein turnover in aging and human disuse atrophy. Scand J Med Sci Sports 20:5–9Google Scholar
  125. Riley DA, Bain JL, Thompson JL, Fitts RH, Widrick JJ, Trappe SW, Trappe TA, Costill DL (2000) Decreased thin filament density and length in human atrophic soleus muscle fibers after spaceflight. J Appl Physiol 88:567–572PubMedGoogle Scholar
  126. Rittweger J, Felsenberg D, Maganaris C, Ferretti JL (2007) Vertical jump performance after 90 days bed rest with and without flywheel resistive exercise, including a 180 days follow-up. Eur J Appl Physiol 100:427–436PubMedCrossRefGoogle Scholar
  127. Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ (2001) Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 3:1009–1013PubMedCrossRefGoogle Scholar
  128. Roy RR, Bello MA, Bouissou P, Edgerton VR (1987) Size and metabolic properties of fibers in rat fast-twitch muscles after hindlimb suspension. J Appl Physiol 62:2348–2357PubMedGoogle Scholar
  129. Rozier CK, Elder JD, Brown M (1979) Prevention of atrophy by isometric exercise of a casted leg. J Sports Med Phys Fitness 19:191–194PubMedGoogle Scholar
  130. Rudnick J, Puttmann B, Tesch PA, Alkner B, Schoser BG, Salanova M, Kirsch K, Gunga HC, Schiffl G, Luck G, Blottner D (2004) Differential expression of nitric oxide synthases (NOS 1-3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest. FASEB J 18:1228–1230Google Scholar
  131. Rummel JA, Sawin CF, Michel EL, Buderer MC, Thornton WT (1975) Exercise and long duration spaceflight through 84 days. J Am Med Womens Assoc 30:173–187PubMedGoogle Scholar
  132. Ryan AS, Dobrovolny CL, Smith GV, Silver KH, Macko RF (2002) Hemiparetic muscle atrophy and increased intramuscular fat in stroke patients. Arch Phys Med Rehabil 83:1703–1707PubMedCrossRefGoogle Scholar
  133. Sargeant AJ, Davies CT, Edwards RH, Maunder C, Young A (1977) Functional and structural changes after disuse of human muscle. Clin Sci Mol Med 52:337–342PubMedGoogle Scholar
  134. Schulze K, Gallagher P, Trappe S (2002) Resistance training preserves skeletal muscle function during unloading in humans. Med Sci Sports Exerc 34:303–313PubMedCrossRefGoogle Scholar
  135. Seynnes OR, Maffiuletti NA, Maganaris CN, de Boer MD, Pensini M, di Prampero PE, Narici MV (2008) Soleus T reflex modulation in response to spinal and tendinous adaptations to unilateral lower limb suspension in humans. Acta Physiol (Oxf) 194:239–251CrossRefGoogle Scholar
  136. Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, Spector E, Feeback DL, Lai D (2004) Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol 97:119–129PubMedCrossRefGoogle Scholar
  137. Shyy JY, Chien S (1997) Role of integrins in cellular responses to mechanical stress and adhesion. Curr Opin Cell Biol 9:707–713PubMedCrossRefGoogle Scholar
  138. Stevens L, Mounier Y, Holy X (1993) Functional adaptation of different rat skeletal muscles to weightlessness. Am J Physiol 264:R770–R776PubMedGoogle Scholar
  139. Stewart CE (2004) The physiology of stem cells: potential for the elderly patient. J Musculoskelet Neuronal Interact 4:179–183PubMedGoogle Scholar
  140. Suzuki Y, Kashihara H, Takenaka K, Kawakubo K, Makita Y, Goto S, Ikawa S, Gunji A (1994) Effects of daily mild supine exercise on physical performance after 20 days bed rest in young persons. Acta Astronaut 33:101–111PubMedCrossRefGoogle Scholar
  141. Talmadge RJ (2000) Myosin heavy chain isoform expression following reduced neuromuscular activity: potential regulatory mechanisms. Muscle Nerve 23:661–679PubMedCrossRefGoogle Scholar
  142. Templeton GH, Padalino M, Manton J, Glasberg M, Silver CJ, Silver P, DeMartino G, Leconey T, Klug G, Hagler H et al (1984) Influence of suspension hypokinesia on rat soleus muscle. J Appl Physiol 56:278–286PubMedGoogle Scholar
  143. Tesch PA, Berg HE (1997) Resistance training in space. Int J Sports Med 18(Suppl 4):S322–S324PubMedCrossRefGoogle Scholar
  144. Tesch PA, Trieschmann JT, Ekberg A (2004) Hypertrophy of chronically unloaded muscle subjected to resistance exercise. J Appl Physiol 96:1451–1458PubMedCrossRefGoogle Scholar
  145. Tesch PA, Berg HE, Bring D, Evans HJ, LeBlanc AD (2005) Effects of 17-day spaceflight on knee extensor muscle function and size. Eur J Appl Physiol 93:463–468PubMedCrossRefGoogle Scholar
  146. Thom JM, Thompson MW, Ruell PA, Bryant GJ, Fonda JS, Harmer AR, De Jonge XA, Hunter SK (2001) Effect of 10-day cast immobilization on sarcoplasmic reticulum calcium regulation in humans. Acta Physiol Scand 172:141–147PubMedCrossRefGoogle Scholar
  147. Thomason DB, Booth FW (1990) Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol 68:1–12PubMedCrossRefGoogle Scholar
  148. Thorton WE, Rummel JA (1977) Muscular deconditioning and its prevention in space flight. In: Johnson RS, Deitlein LF (eds) Biomedical results from skylab. NASA, Washington, DC, pp 191–197Google Scholar
  149. Trappe SW, Trappe TA, Lee GA, Widrick JJ, Costill DL, Fitts RH (2001) Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function. J Appl Physiol 91:57–64PubMedGoogle Scholar
  150. Trappe S, Trappe T, Gallagher P, Harber M, Alkner B, Tesch P (2004) Human single muscle fibre function with 84 day bed-rest and resistance exercise. J Physiol 557:501–513PubMedCrossRefGoogle Scholar
  151. Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW (2007) Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol (Oxf) 191:147–159CrossRefGoogle Scholar
  152. Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, Ferrando A (1995) Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 269:E820–E826PubMedGoogle Scholar
  153. Veldhuizen JW, Verstappen FT, Vroemen JP, Kuipers H, Greep JM (1993) Functional and morphological adaptations following four weeks of knee immobilization. Int J Sports Med 14:283–287PubMedCrossRefGoogle Scholar
  154. Wade CE, Stanford KI, Stein TP, Greenleaf JE (2005) Intensive exercise training suppresses testosterone during bed rest. J Appl Physiol 99:59–63PubMedCrossRefGoogle Scholar
  155. Wang H, Casaburi R, Taylor WE, Aboellail H, Storer TW, Kopple JD (2005) Skeletal muscle mRNA for IGF-IEa, IGF-II, and IGF-I receptor is decreased in sedentary chronic hemodialysis patients. Kidney Int 68:352–361PubMedCrossRefGoogle Scholar
  156. White MJ, Davies CT, Brooksby P (1984) The effects of short-term voluntary immobilization on the contractile properties of the human triceps surae. Q J Exp Physiol 69:685–691PubMedGoogle Scholar
  157. Widrick JJ, Romatowski JG, Bain JL, Trappe SW, Trappe TA, Thompson JL, Costill DL, Riley DA, Fitts RH (1997) Effect of 17 days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers. Am J Physiol 273:C1690–C1699PubMedGoogle Scholar
  158. Widrick JJ, Knuth ST, Norenberg KM, Romatowski JG, Bain JL, Riley DA, Karhanek M, Trappe SW, Trappe TA, Costill DL, Fitts RH (1999) Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres. J Physiol 516(Pt 3):915–930PubMedCrossRefGoogle Scholar
  159. Widrick JJ, Trappe SW, Romatowski JG, Riley DA, Costill DL, Fitts RH (2002) Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function. J Appl Physiol 93:354–360PubMedGoogle Scholar
  160. Wilkie DR (1949) The relation between force and velocity in human muscle. J Physiol 110:249–280PubMedGoogle Scholar
  161. Wineski LE, von Deutsch DA, Abukhalaf IK, Pitts SA, Potter DE, Paulsen DF (2002) Muscle-specific effects of hindlimb suspension and clenbuterol in mature male rats. Cells Tissues Organs 171:188–198PubMedCrossRefGoogle Scholar
  162. Yamashita-Goto K, Okuyama R, Honda M, Kawasaki K, Fujita K, Yamada T, Nonaka I, Ohira Y, Yoshioka T (2001) Maximal and submaximal forces of slow fibers in human soleus after bed rest. J Appl Physiol 91:417–424PubMedGoogle Scholar
  163. Yoshida N, Sairyo K, Sasa T, Fukunaga M, Koga K, Ikata T, Yasui N (2003) Electrical stimulation prevents deterioration of the oxidative capacity of disuse-atrophied muscles in rats. Aviat Space Environ Med 74:207–211PubMedGoogle Scholar
  164. Zachwieja JJ, Smith SR, Lovejoy JC, Rood JC, Windhauser MM, Bray GA (1999) Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest. J Clin Endocrinol Metab 84:207–212PubMedCrossRefGoogle Scholar
  165. Zange J, Muller K, Schuber M, Wackerhage H, Hoffmann U, Gunther RW, Adam G, Neuerburg JM, Sinitsyn VE, Bacharev AO, Belichenko OI (1997) Changes in calf muscle performance, energy metabolism, and muscle volume caused by long-term stay on space station MIR. Int J Sports Med 18(Suppl 4):S308–S309PubMedCrossRefGoogle Scholar
  166. Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, McPherron AC, Wolfman NM, Lee SJ (2002) Induction of cachexia in mice by systemically administered myostatin. Science 296:1486–1488PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Institute for Biomedical Research into Human Movement and Health, Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK
  2. 2.Division of Applied Medicine, School of Medicine and DentistryUniversity of AberdeenScotlandUK

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