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Exercise Countermeasures to Neuromuscular Deconditioning in Spaceflight

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Abstract

The mechanical unloading of spaceflight elicits a host of physiological adaptations including reductions in muscle mass, muscle strength, and muscle function and alterations in central interpretation of visual, vestibular, and proprioceptive information. Upon return to a terrestrial, gravitational environment, these result in reduced function and performance, the potential consequences of which will be exacerbated during exploration missions to austere and distant destinations such as the moon and Mars. Exercise is a potent countermeasure to unloading‐induced physiological maladaptations and has been employed since the early days of spaceflight. In‐flight exercise hardware has evolved from rudimentary and largely ineffective devices to the current suite onboard the International Space Station (ISS) comprised of a cycle ergometer, treadmill, and resistance exercise device; these contemporary devices have either fully protected or significantly attenuated neuromuscular degradation in spaceflight. However, unlike current microgravity operations on the ISS, future exploration missions will include surface operations in partial gravity environments, which will require greater physiological capacity and work output of their crews. For these flights, it is critical to identify physiological thresholds below which task performance will be impaired and to develop exercise countermeasures—both pre‐ and in‐flight—to ensure that crewmembers are able to safely and effectively complete physically demanding mission objectives. © 2020 American Physiological Society. Compr Physiol 10:171‐196, 2020.

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Figure 1. Figure 1. The exercise device used on some Apollo missions was based on the Exer‐Genie (Exer‐Genie, Inc., Fullerton, CA). Within the cylinder, the nylon cords rotate around a shaft, developing controlled resistance. The cords are attached to loop handles. When not in use, the flight device was stored in a cloth bag (inset).
Figure 2. Figure 2. Ground reaction forces during an iRED squat in 1‐g 8.
Figure 3. Figure 3. Ground reaction forces during a free‐weight (Smith machine) squat in 1‐g 8.
Figure 4. Figure 4. (A) The Advanced Resistive Exercise Device (ARED), pictured on the ground; (B) ARED deployed on the International Space Station with a crewmember performing a deadlift.
Figure 5. Figure 5. The second‐generation treadmill (T2) on the International Space Station; the crewmember is loaded via a harness and bungee cord system.
Figure 6. Figure 6. The Cycle Ergometer with Vibration Isolation System (CEVIS) on the International Space Station. The crewmember clips into the pedals via cleated shoes and stabilizes himself using handholds on the frame; there is no seat/saddle.
Figure 7. Figure 7. (A) Scatter plot of time to complete the course (TCC) for 18 long‐duration subjects (6‐month exposure to spaceflight) showing a 48% increase in time to traverse the obstacle course 1 day after landing. (B) Diagram of obstacle course. (C) Recovery of function took an average of 15 days to return to within 95% of their preflight level of performance.
Figure 8. Figure 8. Results from two tests of postural stability (top two rows) along with an assessment of lower body muscle function (bottom row) in long‐duration ISS crewmembers (Spaceflight group) and bed rest subjects who performed exercise while in bed (Exercise group) and those who did not exercise (Control group).
Figure 9. Figure 9. A subset of prominent physiological systems that are (i) altered by the microgravity of spaceflight and (ii) amenable to protection via exercise countermeasures.


Figure 1. The exercise device used on some Apollo missions was based on the Exer‐Genie (Exer‐Genie, Inc., Fullerton, CA). Within the cylinder, the nylon cords rotate around a shaft, developing controlled resistance. The cords are attached to loop handles. When not in use, the flight device was stored in a cloth bag (inset).


Figure 2. Ground reaction forces during an iRED squat in 1‐g 8.


Figure 3. Ground reaction forces during a free‐weight (Smith machine) squat in 1‐g 8.


Figure 4. (A) The Advanced Resistive Exercise Device (ARED), pictured on the ground; (B) ARED deployed on the International Space Station with a crewmember performing a deadlift.


Figure 5. The second‐generation treadmill (T2) on the International Space Station; the crewmember is loaded via a harness and bungee cord system.


Figure 6. The Cycle Ergometer with Vibration Isolation System (CEVIS) on the International Space Station. The crewmember clips into the pedals via cleated shoes and stabilizes himself using handholds on the frame; there is no seat/saddle.


Figure 7. (A) Scatter plot of time to complete the course (TCC) for 18 long‐duration subjects (6‐month exposure to spaceflight) showing a 48% increase in time to traverse the obstacle course 1 day after landing. (B) Diagram of obstacle course. (C) Recovery of function took an average of 15 days to return to within 95% of their preflight level of performance.


Figure 8. Results from two tests of postural stability (top two rows) along with an assessment of lower body muscle function (bottom row) in long‐duration ISS crewmembers (Spaceflight group) and bed rest subjects who performed exercise while in bed (Exercise group) and those who did not exercise (Control group).


Figure 9. A subset of prominent physiological systems that are (i) altered by the microgravity of spaceflight and (ii) amenable to protection via exercise countermeasures.
References
 1.Ade CJ, Broxterman RM, Craig JC, Schlup SJ, Wilcox SL, Barstow TJ. Relationship between simulated extravehicular activity tasks and measurements of physical performance. Respir Physiol Neurobiol 203: 19‐27, 2014.
 2.Ade CJ, Broxterman RM, Craig JC, Schlup SJ, Wilcox SL, Barstow TJ. Standardized exercise tests and simulated terrestrial mission task performance. Aerosp Med Hum Perform 86 (11): 982‐989, 2015.
 3.Ade CJ, Broxterman RM, Craig JC, Schlup SJ, Wilcox SL, Warren S, Kuehl P, Gude D, Jia C, Barstow TJ. Prediction of lunar‐ and martian‐based intra‐ and site‐to‐site task performance. Aerosp Med Hum Perform 87 (4): 367‐374, 2016.
 4.Akima H, Kubo K, Kanehisa H, Suzuki Y, Gunji A, Fukunaga T. Leg‐press resistance training during 20 days of 6 degrees head‐down‐tilt bed rest prevents muscle deconditioning. Eur J Appl Physiol 82 (1‐2): 30‐38, 2000.
 5.Alkner BA, Berg HE, Kozlovskaya I, Sayenko D, Tesch PA. Effects of strength training, using a gravity‐independent exercise system, performed during 110 days of simulated space station confinement. Eur J Appl Physiol 90 (1‐2): 44‐49, 2003.
 6.Alkner BA, Tesch PA. Efficacy of a gravity‐independent resistance exercise device as a countermeasure to muscle atrophy during 29‐day bed rest. Acta Physiol Scand 181 (3): 345‐357, 2004.
 7.Alkner BA, Tesch PA. 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 (3): 294‐305, 2004.
 8.Amonette WE, Bentley JR, Lee SMC, Loehr JA, Schneider SM. Ground reaction force and mechanical differences between the interim resistive exercise device (iRED) and smith machine while performing a squat. NASA Technical Paper, TP‐212063, Washington, DC, 2004.
 9.Attaix D, Baracos VE, Pichard C. Muscle wasting: A crosstalk between protein synthesis and breakdown signalling. Curr Opin Clin Nutr Metab Care 15 (3): 209‐210, 2012.
 10.Bamman MM, Clarke MS, Feeback DL, Talmadge RJ, Stevens BR, Lieberman SA, Greenisen MC. Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution. J Appl Physiol (1985) 84 (1): 157‐163, 1998.
 11.Bamman MM, Clarke MS, Talmadge RJ, Feeback DL. Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms. Electrophoresis 20 (3): 466‐468, 1999.
 12.Bamman MM, Hunter GR, Stevens BR, Guilliams ME, Greenisen MC. Resistance exercise prevents plantar flexor deconditioning during bed rest. Med Sci Sports Exerc 29 (11): 1462‐1468, 1997.
 13.Bastiaanse CM, Duysens J, Dietz V. Modulation of cutaneous reflexes by load receptor input during human walking. Exp Brain Res 135 (2): 189‐198, 2000.
 14.Belavy DL, Ohshima H, Rittweger J, Felsenberg D. High‐intensity flywheel exercise and recovery of atrophy after 90 days bed‐rest. BMJ Open Sport Exerc Med 3 (1): e000196, 2017.
 15.Berg HE. Effects of unloading on skeletal muscle mass and function in man. [Ph.D. Thesis]. Stockholm: Karolinska Institute, 1997.
 16.Berg HE, Dudley GA, Haggmark T, Ohlsen H, Tesch PA. Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol 70 (4): 1882‐1885, 1991.
 17.Berg HE, Dudley GA, Hather B, Tesch PA. Work capacity and metabolic and morphologic characteristics of the human quadriceps muscle in response to unloading. Clin Physiol 13 (4): 337‐347, 1993.
 18.Berg HE, Eiken O, Miklavcic L, Mekjavic IB. Hip, thigh and calf muscle atrophy and bone loss after 5‐week bedrest inactivity. Eur J Appl Physiol 99 (3): 283‐289, 2007.
 19.Berg HE, Larsson L, Tesch PA. Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol (1985) 82 (1): 182‐188, 1997.
 20.Berger M, Mescheriakov S, Molokanova E, Lechner‐Steinleitner S, Seguer N, Kozlovskaya I. Pointing arm movements in short‐ and long‐term spaceflights. Aviat Space Environ Med 68 (9): 781‐787, 1997.
 21.Berry P, Berry I, Manelfe C. Magnetic resonance imaging evaluation of lower limb muscles during bed rest—a microgravity simulation model. Aviat Space Environ Med 64 (3 Pt 1): 212‐218, 1993.
 22.Biolo G, Agostini F, Simunic B, Sturma M, Torelli L, Preiser JC, Deby‐Dupont G, Magni P, Strollo F, di Prampero P, Guarnieri G, Mekjavic IB, Pisot R, Narici MV. Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest. Am J Clin Nutr 88 (4): 950‐958, 2008.
 23.Biolo G, Ciocchi B, Stulle M, Bosutti A, Barazzoni R, Zanetti M, Antonione R, Lebenstedt M, Platen P, Heer M, Guarnieri G. Calorie restriction accelerates the catabolism of lean body mass during 2 wk of bed rest. Am J Clin Nutr 86 (2): 366‐372, 2007.
 24.Black FO, Paloski WH. Computerized dynamic posturography: what have we learned from space? Otolaryngol Head Neck Surg 118 (3 Pt 2): S45‐S51, 1998.
 25.Bloomberg JJ, Mulavara AP. Changes in walking strategies after spaceflight. IEEE Eng Med Biol Mag 22 (2): 58‐62, 2003.
 26.Bloomberg JJ, Peters BT, Cohen HS, Mulavara AP. Enhancing astronaut performance using sensorimotor adaptability training. Front Syst Neurosci 9: 129, 2015.
 27.Bloomberg JJ, Peters BT, Smith SL, Huebner WP, Reschke MF. Locomotor head‐trunk coordination strategies following space flight. J Vestib Res 7 (2‐3): 161‐177, 1997.
 28.Bloomberg JJ, Reschke MF, Clement GR, Mulavara AP, Taylor LC. Risk of impaired control of spacecraft/associated systems and decreased mobility due to vestibular/sensorimotor alterations associated with spaceflight. In: Human Research Program, Human Health Countermeasures Element. Houston TX: National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, 2016.
 29.Bottaro M, Machado SN, Nogueira W, Scales R, Veloso J. Effect of high versus low‐velocity resistance training on muscular fitness and functional performance in older men. Eur J Appl Physiol 99 (3): 257‐264, 2007.
 30.Brandenburg JP, Docherty D. The effects of accentuated eccentric loading on strength, muscle hypertrophy, and neural adaptations in trained individuals. J Strength Cond Res 16 (1): 25‐32, 2002.
 31.Brocca L, Cannavino J, Coletto L, Biolo G, Sandri M, Bottinelli R, Pellegrino MA. The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms. J Physiol 590 (Pt 20): 5211‐5230, 2012.
 32.Brooks N, Cloutier GJ, Cadena SM, Layne JE, Nelsen CA, Freed AM, Roubenoff R, Castaneda‐Sceppa C. 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 (1985) 105 (1): 241‐248, 2008.
 33.Buderer MC, Rummel JA, Sawin CF, Mauldin DG. Use of the single‐breath method of estimating cardiac output during exercise‐stress testing. Aerosp Med 44 (7): 756‐763, 1973.
 34.Campbell MR, Charles JB. Historical review of lower body negative pressure research in space medicine. Aerosp Med Hum Perform 86 (7): 633‐640, 2015.
 35.Campos GE, Luecke TJ, Wendeln HK, Toma K, Hagerman FC, Murray TF, Ragg KE, Ratamess NA, Kraemer WJ, Staron RS. Muscular adaptations in response to three different resistance‐training regimens: Specificity of repetition maximum training zones. Eur J Appl Physiol 88 (1‐2): 50‐60, 2002.
 36.Carriot J, Jamali M, Cullen KE. Rapid adaptation of multisensory integration in vestibular pathways. Front Syst Neurosci 9: 59, 2015.
 37.Cescon C, Gazzoni M. Short term bed‐rest reduces conduction velocity of individual motor units in leg muscles. J Electromyogr Kinesiol 20 (5): 860‐867, 2010.
 38.Churchward‐Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. Supplementation of a suboptimal protein dose with leucine or essential amino acids: Effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol 590 (Pt 11): 2751‐2765, 2012.
 39.Clement G. Evidence report: Artificial gravity. In: Human Research Program, Human Health Countermeasures Element. Houston, TX: National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, 2015.
 40.Clement G, Reschke MF. Neuroscience in Space. New York, NY: Springer Science & Business Media, 2008.
 41.Clement GR, Bukley AP, Paloski WH. Artificial gravity as a countermeasure for mitigating physiological deconditioning during long‐duration space missions. Front Syst Neurosci 9: 92, 2015.
 42.Colliander EB, Tesch PA. Effects of eccentric and concentric muscle actions in resistance training. Acta Physiol Scand 140 (1): 31‐39, 1990.
 43.Courtine G, Papaxanthis C, Pozzo T. Prolonged exposure to microgravity modifies limb endpoint kinematics during the swing phase of human walking. Neurosci Lett 332 (1): 70‐74, 2002.
 44.Courtine G, Pozzo T. Recovery of the locomotor function after prolonged microgravity exposure. I. Head‐trunk movement and locomotor equilibrium during various tasks. Exp Brain Res 158 (1): 86‐99, 2004.
 45.Cree MG, Paddon‐Jones D, Newcomer BR, Ronsen O, Aarsland A, Wolfe RR, Ferrando A. Twenty‐eight‐day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides. Metabolism 59 (5): 703‐710, 2010.
 46.Davis BL, Cavanagh PR, Sommer HJ 3rd, Wu G. Ground reaction forces during locomotion in simulated microgravity. Aviat Space Environ Med 67 (3): 235‐242, 1996.
 47.de Boer MD, Maganaris CN, Seynnes OR, Rennie MJ, Narici MV. Time course of muscular, neural and tendinous adaptations to 23 day unilateral lower‐limb suspension in young men. J Physiol 583 (Pt 3): 1079‐1091, 2007.
 48.de Boer MD, Selby A, Atherton P, Smith K, Seynnes OR, Maganaris CN, Maffulli N, Movin T, Narici MV, Rennie MJ. The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse. J Physiol 585 (Pt 1): 241‐251, 2007.
 49.Devkota S, Layman DK. Protein metabolic roles in treatment of obesity. Curr Opin Clin Nutr Metab Care 13 (4): 403‐407, 2010.
 50.Dickinson JM, Fry CS, Drummond MJ, Gundermann DM, Walker DK, Glynn EL, Timmerman KL, Dhanani S, Volpi E, Rasmussen BB. Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids. J Nutr 141 (5): 856‐862, 2011.
 51.Dietlein LF. Summary and conclusions. In: Johnston RS, Dietlein LF, Berry CA, editors. Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 573‐580.
 52.Dietz V. Interaction between central programs and afferent input in the control of posture and locomotion. J Biomech 29 (7): 841‐844, 1996.
 53.Dietz V, Duysens J. Significance of load receptor input during locomotion: A review. Gait Posture 11 (2): 102‐110, 2000.
 54.Dietz V, Horstmann GA, Trippel M, Gollhofer A. Human postural reflexes and gravity—An underwater simulation. Neurosci Lett 106 (3): 350‐355, 1989.
 55.Dietz V, Muller R, Colombo G. Locomotor activity in spinal man: Significance of afferent input from joint and load receptors. Brain 125 (Pt 12): 2626‐2634, 2002.
 56.Dirks ML, Wall BT, van de Valk B, Holloway TM, Holloway GP, Chabowski A, Goossens GH, van Loon LJ. One week of bed rest leads to substantial muscle atrophy and induces whole‐body insulin resistance in the absence of skeletal muscle lipid accumulation. Diabetes 65 (10): 2862‐2875, 2016.
 57.Dolkas CB, Greenleaf JE. Insulin and glucose responses during bed rest with isotonic and isometric exercise. J Appl Physiol 43 (6): 1033‐1038, 1977.
 58.Donelan JM, Kram R. The effect of reduced gravity on the kinematics of human walking: A test of the dynamic similarity hypothesis for locomotion. J Exp Biol 200 (Pt 24): 3193‐3201, 1997.
 59.Drummond MJ, Dickinson JM, Fry CS, Walker DK, Gundermann DM, Reidy PT, Timmerman KL, Markofski MM, Paddon‐Jones D, Rasmussen BB, Volpi E. Bed rest impairs skeletal muscle amino acid transporter expression, mtorc1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab 302 (9): E1113‐E1122, 2012.
 60.Dudley GA, Duvoisin MR, Adams GR, Convertino VA, Buchanan P. Alterations of the in vivo torque‐velocity relationship of human skeletal muscle following 30 days exposure to simulated microgravity. Aviat Space Environ Med 60: 659‐663, 1989.
 61.Dudley GA, Duvoisin MR, Adams GR, Meyer RA, Belew AH, Buchanan P. Adaptations to unilateral lower limb suspension in humans. Aviat Space Environ Med 63: 678‐683, 1992.
 62.Dudley GA, Gollnick PD, Convertino VA, Buchanan P. Changes of muscle function and size with bedrest. Physiologist 32 (1 Suppl): S65‐S66, 1989.
 63.Duysens J, Clarac F, Cruse H. Load‐regulating mechanisms in gait and posture: Comparative aspects. Physiol Rev 80 (1): 83‐133, 2000.
 64.English KL, Lee SM, Loehr JA, Ploutz‐Snyder RJ, Ploutz‐Snyder LL. Isokinetic strength changes following long‐duration spaceflight on the ISS. Aerosp Med Hum Perform 86 (12 Suppl): A68‐A77, 2015.
 65.English KL, Loehr JA, Lee SM, Smith SM. Early‐phase musculoskeletal adaptations to different levels of eccentric resistance after 8 weeks of lower body training. Eur J Appl Physiol, 2014.
 66.English KL, Mettler JA, Ellison JB, Mamerow MM, Arentson‐Lantz E, Pattarini JM, Ploutz‐Snyder R, Sheffield‐Moore M, Paddon‐Jones D. Leucine partially protects muscle mass and function during bed rest in middle‐aged adults. Am J Clin Nutr 103 (2): 465‐473, 2016.
 67.English KL, Paddon‐Jones D. Protecting muscle mass and function in older adults during bed rest. Curr Opin Clin Nutr Metab Care 13 (1): 34‐39, 2010.
 68.Ferrando AA, Lane HW, Stuart CA, Davis‐Street J, Wolfe RR. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol 270 (4 Pt 1): E627‐E633, 1996.
 69.Ferrando AA, Paddon‐Jones D, Hays NP, Kortebein P, Ronsen O, Williams RH, McComb A, Symons TB, Wolfe RR, Evans W. EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr 29 (1): 18‐23, 2010.
 70.Ferrando AA, Stuart CA, Brunder DG, Hillman GR. Magnetic resonance imaging quantitation of changes in muscle volume during 7 days of strict bed rest. Aviat Space Environ Med 66 (10): 976‐981, 1995.
 71.Ferrando AA, Tipton KD, Bamman MM, Wolfe RR. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J Appl Physiol (1985) 82 (3): 807‐810, 1997.
 72.Finch L, Barbeau H, Arsenault B. Influence of body weight support on normal human gait: Development of a gait retraining strategy. Phys Ther 71 (11): 842‐855; discussion 855–846, 1991.
 73.Fitts RH, Trappe SW, Costill DL, Gallagher PM, Creer AC, Colloton PA, Peters JR, Romatowski JG, Bain JL, Riley DA. Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres. J Physiol 588 (Pt 18): 3567‐3592, 2010.
 74.Fouad K, Bastiaanse CM, Dietz V. Reflex adaptations during treadmill walking with increased body load. Exp Brain Res 137 (2): 133‐140, 2001.
 75.Gallagher P, Trappe S, Harber M, Creer A, Mazzetti S, Trappe T, Alkner B, Tesch P. Effects of 84‐days of bedrest and resistance training on single muscle fibre myosin heavy chain distribution in human vastus lateralis and soleus muscles. Acta Physiol Scand 185 (1): 61‐69, 2005.
 76.Garrett‐Bakelman FE, Darshi M, Green SJ, Gur RC, Lin L, Macias BR, McKenna MJ, Meydan C, Mishra T, Nasrini J, Piening BD, Rizzardi LF, Sharma K, Siamwala JH, Taylor L, Vitaterna MH, Afkarian M, Afshinnekoo E, Ahadi S, Ambati A, Arya M, Bezdan D, Callahan CM, Chen S, Choi AMK, Chlipala GE, Contrepois K, Covington M, Crucian BE, De Vivo I, Dinges DF, Ebert DJ, Feinberg JI, Gandara JA, George KA, Goutsias J, Grills GS, Hargens AR, Heer M, Hillary RP, Hoofnagle AN, Hook VYH, Jenkinson G, Jiang P, Keshavarzian A, Laurie SS, Lee‐McMullen B, Lumpkins SB, MacKay M, Maienschein‐Cline MG, Melnick AM, Moore TM, Nakahira K, Patel HH, Pietrzyk R, Rao V, Saito R, Salins DN, Schilling JM, Sears DD, Sheridan CK, Stenger MB, Tryggvadottir R, Urban AE, Vaisar T, Van Espen B, Zhang J, Ziegler MG, Zwart SR, Charles JB, Kundrot CE, GBI S, Bailey SM, Basner M, Feinberg AP, SMC L, Mason CE, Mignot E, Rana BK, Smith SM, Snyder MP, Turek FW. The NASA Twins Study: A multidimensional analysis of a year‐long human spaceflight. Science 364 (6436), eaau8650, 2019.
 77.Genc KO, Gopalakrishnan R, Kuklis MM, Maender CC, Rice AJ, Bowersox KD, Cavanagh PR. Foot forces during exercise on the International Space Station. J Biomech 43 (15): 3020‐3027, 2010.
 78.Glasauer S, Amorim MA, Bloomberg JJ, Reschke MF, Peters BT, Smith SL, Berthoz A. Spatial orientation during locomotion [correction of locomation] following space flight. Acta Astronaut 36 (8‐12): 423‐431, 1995.
 79.Glover EI, Phillips SM, Oates BR, Tang JE, Tarnopolsky MA, Selby A, Smith K, Rennie MJ. Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion. J Physiol 586 (Pt 24): 6049‐6061, 2008.
 80.Glover EI, Yasuda N, Tarnopolsky MA, Abadi A, Phillips SM. Little change in markers of protein breakdown and oxidative stress in humans in immobilization‐induced skeletal muscle atrophy. Appl Physiol Nutr Metab 35 (2): 125‐133, 2010.
 81.Gogia P, Schneider VS, LeBlanc AD, Krebs J, Kasson C, Pientok C. Bed rest effect on extremity muscle torque in healthy men. Arch Phys Med Rehabil 69 (12): 1030‐1032, 1988.
 82.Gopalakrishnan R, Genc KO, Rice AJ, Lee SM, Evans HJ, Maender CC, Ilaslan H, Cavanagh PR. Muscle volume, strength, endurance, and exercise loads during 6‐month missions in space. Aviat Space Environ Med 81 (2): 91‐102, 2010.
 83.Grana EA, Chiou‐Tan F, Jaweed MM. Endplate dysfunction in healthy muscle following a period of disuse. Muscle Nerve 19 (8): 989‐993, 1996.
 84.Greenisen MC, Hayes JC, Siconolfi SF, Moore AD. Functional performance evaluation. In: Sawin CF, Taylor GR, Smith WL, editors. Extended Duration Orbiter Medical Project: Final Report 1989–1995. Houston, TX: National Aeronautics and Space Administration, 1999.
 85.Grigoryeva LS, Kozlovskaya IB. Effects of 7‐day immersion hypokinesia on characteristics of precision of movements. Kosm Biol Aviakosm Med 19: 38‐42, 1985.
 86.Grindeland RE, Kraemer WJ, Hymer WC. Two types of rat pituitary somatotrophs secrete growth hormone with different biological and immunological profiles. Growth Horm IGF Res 36: 52‐56, 2017.
 87.Hackney KJ, Scott JM, Hanson AM, English KL, Downs ME, Ploutz‐Snyder LL. The astronaut‐athlete: Optimizing human performance in space. J Strength Cond Res 29 (12): 3531‐3545, 2015.
 88.Harkema SJ, Hurley SL, Patel UK, Requejo PS, Dobkin BH, Edgerton VR. Human lumbosacral spinal cord interprets loading during stepping. J Neurophysiol 77 (2): 797‐811, 1997.
 89.Hather BM, Adams GR, Tesch PA, Dudley GA. Skeletal muscle responses to lower limb suspension in humans. J Appl Physiol 72 (4): 1493‐1498, 1992.
 90.Hikida RS, Gollnick PD, Dudley GA, Convertino VA, Buchanan P. Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity. Aviat Space Environ Med 60 (7): 664‐670, 1989.
 91.Hortobagyi T, Dempsey L, Fraser D, Zheng D, Hamilton G, Lambert J, Dohm L. Changes in muscle strength, muscle fibre size and myofibrillar gene expression after immobilization and retraining in humans. J Physiol 524 (Pt 1): 293‐304, 2000.
 92.Hughson RL, Robertson AD, Arbeille P, Shoemaker JK, Rush JW, Fraser KS, Greaves DK. Increased postflight carotid artery stiffness and inflight insulin resistance resulting from 6‐mo spaceflight in male and female astronauts. Am J Physiol Heart Circ Physiol 310 (5): H628‐H638, 2016.
 93.Human Research Program. Evidence Book: Risk of Impaired Performance Due to Reduced Muscle Mass, Strength, and Endurance. Houston, TX: National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, 2008.
 94.Il'ina‐Kakuyeva YI, Portugalov VV, Krivenkov NP, Kakurin LI, Chtrcpahkin MA, Fedorenko GT, Permshin VI, Shaposhnikov YA. Effects of physical conditioning and electric stimulation on metabolic processes in the soleus muscle and structure thereof in hypokinetic man. Kosm Biol Aviakosm Med 13: 35‐38, 1979.
 95.Ivanenko YP, Grasso R, Macellari V, Lacquaniti F. Control of foot trajectory in human locomotion: Role of ground contact forces in simulated reduced gravity. J Neurophysiol 87 (6): 3070‐3089, 2002.
 96.Jain V, Wood SJ, Feiveson AH, Black FO, Paloski WH. Diagnostic accuracy of dynamic posturography testing after short‐duration spaceflight. Aviat Space Environ Med 81 (7): 625‐631, 2010.
 97.Johnston RS. Introduction. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 3‐7.
 98.Katkovskiy BS, Machinskiy GV, Toman PS, Danilova VI, Demida BF. Man's physical performance after 30‐day hypokinesia with countermeasures. Kosm Biol Aviakosm Med 8: 43‐47, 1974.
 99.Katsanos CS, Kobayashi H, Sheffield‐Moore M, Aarsland A, Wolfe RR. Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 82 (5): 1065‐1073, 2005.
 100.Katsanos CS, Kobayashi H, Sheffield‐Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab 291 (2): E381‐E387, 2006.
 101.Kawakami Y, Akima H, Kubo K, Muraoka Y, Hasegawa H, Kouzaki M, Imai M, Suzuki Y, Gunji A, Kanehisa H, Fukunaga T. Changes in muscle size, architecture, and neural activation after 20 days of bed rest with and without resistance exercise. Eur J Appl Physiol 84 (1‐2): 7‐12, 2001.
 102.Kim TS, Rahn H, Farhi LE. Estimation of true venous and arterial PCO2 by gas analysis of a single breath. J Appl Physiol 21 (4): 1338‐1344, 1966.
 103.Kornilova LN. Vestibular function and sensory interaction in altered gravity. Adv Space Biol Med 6: 275‐313, 1997.
 104.Kortebein P, Ferrando A, Lombeida J, Wolfe R, Evans WJ. Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 297 (16): 1772‐1774, 2007.
 105.Kortebein P, Symons TB, Ferrando A, Paddon‐Jones D, Ronsen O, Protas E, Conger S, Lombeida J, Wolfe R, Evans WJ. Functional impact of 10 days of bed rest in healthy older adults. J Gerontol A Biol Sci Med Sci 63 (10): 1076‐1081, 2008.
 106.Korth DW. Exercise countermeasure hardware evolution on ISS: The first decade. Aerosp Med Hum Perform 86 (12 Suppl): A7‐A13, 2015.
 107.Koryak Y. Contractile properties of the human triceps surae muscle during simulated weightlessness. Eur J Appl Physiol Occup Physiol 70 (4): 344‐350, 1995.
 108.Koryak Y. “Dry” immersion induces neural and contractile adaptations in the human triceps surae muscle. Environ Med 46 (1‐2): 17‐27, 2002.
 109.Kozlovskaya IB, Aslanova IF, Barmin VA. The nature and characteristics of gravitational ataxia. Physiologist 510 (Pt. 1): 287‐295, 1983.
 110.Kozlovskaya IB, Aslanova IF, Grigorieva LS, Kreidich Y. Experimental analysis of motor effects of weightlessness. Physiologist 25: S108‐S109, 1982.
 111.Kozlovskaya IB, Grigoriev AI. Russian system of countermeasures on board of the International Space Station (ISS): The first results. Acta Astronaut 55 (3‐9): 233‐237, 2004.
 112.Kozlovskaya IB, Grigoriev AI, Stepantzov VI. Countermeasure of the negative effects of weightlessness on physical systems in long‐term space flights. Acta Astronaut 36 (8‐12): 661‐668, 1995.
 113.Kozlovskaya IB, Kreidich YV, Oganov VS, Koserenko OP. Pathophysiology of motor functions in prolonged manned space flights. Acta Astronaut 8 (9‐10): 1059‐1072, 1981.
 114.Kozlovskaya IB, Sayenko IV, Sayenko DG, Miller TF, Khusnutdinova DR, Melnik KA. Role of support afferentation in control of the tonic muscle activity. Acta Astronaut 60 (4‐7): 285‐294, 2007.
 115.Kozlovskaya IB, Yarmanova EN, Yegorov AD, Stepantsov VI, Fomina EV, Tomilovaskaya ES. Russian countermeasure systems for adverse effects of microgravity on long‐duration ISS flights. Aerosp Med Hum Perform 86 (12 Suppl): A24‐A31, 2015.
 116.Kramer A, Kummel J, Mulder E, Gollhofer A, Frings‐Meuthen P, Gruber M. High‐intensity jump training is tolerated during 60 days of bed rest and is very effective in preserving leg power and lean body mass: An overview of the Cologne RSL Study. PLoS One 12 (1): e0169793, 2017.
 117.Lackner JR, DiZio P. Gravitoinertial force level affects the appreciation of limb position during muscle vibration. Brain Res 592 (1‐2): 175‐180, 1992.
 118.Lafortune MA, Lake MJ, Hennig EM. Differential shock transmission response of the human body to impact severity and lower limb posture. J Biomech 29 (12): 1531‐1537, 1996.
 119.Laughlin MS, Guilliams ME, Nieschwitz BA, Hoellen D. Functional fitness testing results following long‐duration ISS missions. Aerosp Med Hum Perform 86 (12 Suppl): A87‐A91, 2015.
 120.Layman DK. Dietary guidelines should reflect new understandings about adult protein needs. Nutr Metab (Lond) 6: 12, 2009.
 121.Layne CS, Forth KE. Plantar stimulation as a possible countermeasure to microgravity‐induced neuromotor degradation. Aviat Space Environ Med 79 (8): 787‐794, 2008.
 122.Layne CS, Lange GW, Pruett CJ, McDonald PV, Merkle LA, Mulavara AP, Smith SL, Kozlovskaya IB, Bloomberg JJ. Adaptation of neuromuscular activation patterns during treadmill walking after long‐duration space flight. Acta Astronaut 43 (3‐6): 107‐119, 1998.
 123.Layne CS, McDonald PV, Bloomberg JJ. Neuromuscular activation patterns during treadmill walking after space flight. Exp Brain Res 113 (1): 104‐116, 1997.
 124.Layne CS, Mulavara AP, McDonald PV, Pruett CJ, Kozlovskaya IB, Bloomberg JJ. Effect of long‐duration spaceflight on postural control during self‐generated perturbations. J Appl Physiol (1985) 90 (3): 997‐1006, 2001.
 125.Layne CS, Mulavara AP, McDonald PV, Pruett CJ, Kozlovskaya IB, Bloomberg JJ. Alterations in human neuromuscular activation during over ground locomotion after long‐duration spaceflight. J Gravit Physiol 11: 1‐16, 2004.
 126.Leach CS, Rambaut PC. Biochemical responses of the skylab crewmen: An overview. In: Johnson RS, Dietlein LF, editors. Biomedical Results from Skylab. U.S. Government Printing Office, (NASA SP‐377). Washington, DC: U.S. Government Printing Office, 1977, p. 204‐216.
 127.LeBlanc A, Gogia P, Schneider V, Krebs J, Schonfeld E, Evans H. Calf muscle area and strength changes after five weeks of horizontal bed rest. Am J Sports Med 16 (6): 624‐629, 1988.
 128.LeBlanc A, Lin C, Shackelford L, Sinitsyn V, Evans H, Belichenko O, Schenkman B, Kozlovskaya I, Oganov V, Bakulin A, Hedrick T, Feeback D. Muscle volume, MRI relaxation times (t2), and body composition after spaceflight. J Appl Physiol (1985) 89 (6): 2158‐2164, 2000.
 129.LeBlanc AD, Schneider VS, Evans HJ, Pientok C, Rowe R, Spector E. Regional changes in muscle mass following 17 weeks of bed rest. J Appl Physiol (1985) 73 (5): 2172‐2178, 1992.
 130.Lee SM, Schneider SM, Boda WL, Watenpaugh DE, Macias BR, Meyer RS, Hargens AR. Supine LBNP exercise maintains exercise capacity in male twins during 30‐d bed rest. Med Sci Sports Exerc 39 (8): 1315‐1326, 2007.
 131.Lee SM, Schneider SM, Boda WL, Watenpaugh DE, Macias BR, Meyer RS, Hargens AR. LBNP exercise protects aerobic capacity and sprint speed of female twins during 30 days of bed rest. J Appl Physiol (1985) 106 (3): 919‐928, 2009.
 132.Link MM. Space Medicine in Project Mercury. Washington, DC: NASA, 1965.
 133.Linnarsson D, Hughson RL, Fraser KS, Clement G, Karlsson LL, Mulder E, Paloski WH, Rittweger J, Wuyts FL, Zange J. Effects of an artificial gravity countermeasure on orthostatic tolerance, blood volumes and aerobic power after short‐term bed rest (br‐ag1). J Appl Physiol (1985) 118 (1): 29‐35, 2015.
 134.Lipman RL, Raskin P, Love T, Triebwasser J, Lecocq FR, Schnure JJ. Glucose intolerance during decreased physical activity in man. Diabetes 21 (2): 101‐107, 1972.
 135.Loehr JA, Guilliams ME, Petersen N, Hirsch N, Kawashima S, Ohshima H. Physical training for long‐duration spaceflight. Aerosp Med Hum Perform 86 (12 Suppl): A14‐A23, 2015.
 136.Loehr JA, Lee SM, English KL, Sibonga J, Smith SM, Spiering BA, Hagan RD. Musculoskeletal adaptations to training with the advanced resistive exercise device. Med Sci Sports Exerc 43 (1): 146‐156, 2011.
 137.Loerch LH. Exercise countermeasures on ISS: Summary and future directions. Aerosp Med Hum Perform 86 (12 Suppl): A92‐A93, 2015.
 138.Lowrey CR, Perry SD, Strzalkowski ND, Williams DR, Wood SJ, Bent LR. Selective skin sensitivity changes and sensory reweighting following short‐duration space flight. J Appl Physiol (1985) 116 (6): 683‐692, 2014.
 139.Mamerow MM, Mettler JA, English KL, Casperson SL, Arentson‐Lantz E, Sheffield‐Moore M, Layman DK, Paddon‐Jones D. Dietary protein distribution positively influences 24‐h muscle protein synthesis in healthy adults. J Nutr 144 (6): 876‐880, 2014.
 140.Marimuthu K, Murton AJ, Greenhaff PL. Mechanisms regulating muscle mass during disuse atrophy and rehabilitation in humans. J Appl Physiol (1985) 110 (2): 555‐560, 2011.
 141.Maxfield ME, Brouha L. Validity of heart rate as an indicator of cardiac strain. J Appl Physiol 18: 1099‐1104, 1963.
 142.McDonald PV, Basdogan C, Bloomberg JJ, Layne CS. Lower limb kinematics during treadmill walking after space flight: Implications for gaze stabilization. Exp Brain Res 112 (2): 325‐334, 1996.
 143.McDonald PV, Bloomberg JJ, Layne CS. A review of adaptive change in musculoskeletal impedance during space flight and associated implications for postflight head movement control. J Vestib Res 7 (2‐3): 239‐250, 1997.
 144.Miller CA, Kofman IS, Brady RR, May‐Phillips TR, Batson CD, Lawrence EL, Taylor LC, Peters BT, Mulavara AP, Feiveson AH, Reschke MF, Bloomberg JJ. Functional task and balance performance in bed rest subjects and astronauts. Aerosp Med Hum Perform 89 (9): 805‐815, 2018.
 145.Miller CA, Peters BT, Brady RR, Richards JR, Ploutz‐Snyder RJ, Mulavara AP, Bloomberg JJ. Changes in toe clearance during treadmill walking after long‐duration spaceflight. Aviat Space Environ Med 81 (10): 919‐928, 2010.
 146.Miller TF, Saenko IV, Popov DV, Vinogradova OL, Kozlovskaya IB. Effect of mechanical stimulation of the support zones of soles on the muscle stiffness in 7‐day dry immersion. J Gravit Physiol 11 (2): P135‐P136, 2004.
 147.Moore AD Jr, Downs ME, Lee SM, Feiveson AH, Knudsen P, Ploutz‐Snyder L. Peak exercise oxygen uptake during and following long‐duration spaceflight. J Appl Physiol (1985) 117 (3): 231‐238, 2014.
 148.Moore AD, Lynn PA, Feiveson AH. The first 10 years of aerobic exercise responses to long‐duration ISS flights. Aerosp Med Hum Perform 86 (12, Suppl 1): 78‐86, 2015.
 149.Moritani T, deVries HA. Neural factors versus hypertrophy in the time course of muscle strength gain. Am J Phys Med 58 (3): 115‐130, 1979.
 150.Mulavara AP, Bloomberg JJ. Identifying head‐trunk and lower limb contributions to gaze stabilization during locomotion. J Vestib Res 12 (5‐6): 255‐269, 2002.
 151.Mulavara AP, Feiveson AH, Fiedler J, Cohen H, Peters BT, Miller C, Brady R, Bloomberg JJ. Locomotor function after long‐duration space flight: Effects and motor learning during recovery. Exp Brain Res 202 (3): 649‐659, 2010.
 152.Mulavara AP, Houser J, Miller C, Bloomberg JJ. Full‐body gaze control mechanisms elicited during locomotion: Effects of VOR adaptation. J Vestib Res 15 (5‐6): 279‐289, 2005.
 153.Mulavara AP, Peters BT, Miller CA, Kofman IS, Reschke MF, Taylor LC, Lawrence EL, Wood SJ, Laurie SS, Lee SMC, Buxton RE, May‐Phillips TR, Stenger MB, Ploutz‐Snyder LL, Ryder JW, Feiveson AH, Bloomberg JJ. Physiological and functional alterations after spaceflight and bed rest. Med Sci Sports Exerc 50 (9): 1961‐1980, 2018.
 154.Mulavara AP, Ruttley T, Cohen HS, Peters BT, Miller C, Brady R, Merkle L, Bloomberg JJ. Vestibular‐somatosensory convergence in head movement control during locomotion after long‐duration space flight. J Vestib Res 22 (2): 153‐166, 2012.
 155.Mulder ER, Gerrits KH, Kleine BU, Rittweger J, Felsenberg D, de Haan A, Stegeman DF. High‐density surface EMG study on the time course of central nervous and peripheral neuromuscular changes during 8 weeks of bed rest with or without resistive vibration exercise. J Electromyogr Kinesiol 19 (2): 208‐218, 2009.
 156.Mulder ER, Horstman AM, Stegeman DF, de Haan A, Belavy DL, Miokovic T, Armbrecht G, Felsenberg D, Gerrits KH. Influence of vibration resistance training on knee extensor and plantar flexor size, strength, and contractile speed characteristics after 60 days of bed rest. J Appl Physiol (1985) 107 (6): 1789‐1798, 2009.
 157.Musienko P, Courtine G, Tibbs JE, Kilimnik V, Savochin A, Garfinkel A, Roy RR, Edgerton VR, Gerasimenko Y. Somatosensory control of balance during locomotion in decerebrated cat. J Neurophysiol 107 (8): 2072‐2082, 2012.
 158.NASA. NASA Space Flight Human‐System Standard Volume 1, Revision A: Crew Health (NASA‐STD‐3001). NASA Johnson Space Center Reports, 2014.
 159.Netreba AI, Khusnutdinova DR, Vinogradova OL, Kozlovskaya IB. Effect of dry immersion in combination with stimulation of foot support zones upon muscle force‐velocity characteristics. J Gravit Physiol 11 (2): P129‐P130, 2004.
 160.Newman DJ, Alexander HL, Webbon BW. Energetics and mechanics for partial gravity locomotion. Aviat Space Environ Med 65 (9): 815‐823, 1994.
 161.Newman DJ, Jackson DK, Bloomberg JJ. Altered astronaut lower limb and mass center kinematics in downward jumping following space flight. Exp Brain Res 117 (1): 30‐42, 1997.
 162.Norcross JR, Clowers KG, Clark T, Harvill L, Morency RM, Stroud LC, Desantis L, Vos JR, Gernhardt ML. Metabolic costs and biomechanics of inclined ambulation and exploration tasks in a planetary suit. NASA Technical Paper, TP‐216125, Washington DC, 2010.
 163.Norcross JR, Lee LR, Clowers KG, Morency RM, Desantis L, De Witt JK, Jones JA, Vos JR, Gernhardt ML. Feasibility of performing a suited 10‐km ambulation on the moon‐‐final report of the EVA Walkback Test (EWT). NASA Technical Paper, Washington, DC, 2009.
 164.Norrbrand L, Fluckey JD, Pozzo M, Tesch PA. Resistance training using eccentric overload induces early adaptations in skeletal muscle size. Eur J Appl Physiol 102 (3): 271‐281, 2008.
 165.Paddon‐Jones D, Leidy H. Dietary protein and muscle in older persons. Curr Opin Clin Nutr Metab Care 17 (1): 5‐11, 2014.
 166.Paddon‐Jones D, Rasmussen BB. Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Metab Care 12 (1): 86‐90, 2009.
 167.Paddon‐Jones D, Sheffield‐Moore M, Cree MG, Hewlings SJ, Aarsland A, Wolfe RR, Ferrando AA. Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. J Clin Endocrinol Metab 91 (12): 4836‐4841, 2006.
 168.Paddon‐Jones D, Sheffield‐Moore M, Urban RJ, Sanford AP, Aarsland A, Wolfe RR, Ferrando AA. Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab 89 (9): 4351‐4358, 2004.
 169.Paloski WH, Black FO, Reschke MF, Calkins DS, Shupert C. Vestibular ataxia following shuttle flights: Effects of microgravity on otolith‐mediated sensorimotor control of posture. Am J Otol 14 (1): 9‐17, 1993.
 170.Paloski WH, Bloomberg JJ, Reschke MF, Harm DL. Spaceflight‐induced changes in posture and locomotion. J Biomech 27 (6): 812, 1994.
 171.Paloski WH, Reschke MF, Black FO, Doxey DD, Harm DL. Recovery of postural equilibrium control following spaceflight. Ann N Y Acad Sci 656: 747‐754, 1992.
 172.Paloski WH, Reschke MF, Feiveson AH. Bed rest and intermittent centrifugation effects on human balance and neuromotor reflexes. Aerosp Med Hum Perform 88 (9): 812‐818, 2017.
 173.Pescatello LS. ACSM'S Guidelines for Exercise Testing and Prescription. 9th ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins, 2014.
 174.Peters BT, Miller CA, Brady RA, Richards JT, Mulavara AP, Bloomberg JJ. Dynamic visual acuity during walking after long‐duration spaceflight. Aviat Space Environ Med 82 (4): 463‐466, 2011.
 175.Ploutz‐Snyder LL, Downs M, Goetchius E, Crowell B, English KL, Ploutz‐Snyder R, Ryder JW, Dillon EL, Sheffield‐Moore M, Scott JM. Exercise training mitigates multisystem deconditioning during bed rest. Med Sci Sports Exerc 50 (9): 1920‐1928, 2018.
 176.Ploutz‐Snyder LL, Downs M, Ryder J, Hackney K, Scott J, Buxton R, Goetchius E, Crowell B. Integrated resistance and aerobic exercise protects fitness during bed rest. Med Sci Sports Exerc 46 (2): 358‐368, 2014.
 177.Poyhonen T, Avela J. Effect of head‐out water immersion on neuromuscular function of the plantarflexor muscles. Aviat Space Environ Med 73 (12): 1215‐1218, 2002.
 178.Pozzo T, Berthoz A, Lefort L. Head stabilization during various locomotor tasks in humans. I. Normal subjects. Exp Brain Res 82 (1): 97‐106, 1990.
 179.Recktenwald MR, Hodgson JA, Roy RR, Riazanski S, McCall GE, Kozlovskaya I, Washburn DA, Fanton JW, Edgerton VR. Effects of spaceflight on rhesus quadrupedal locomotion after return to 1g. J Neurophysiol 81 (5): 2451‐2463, 1999.
 180.Res PT, Groen B, Pennings B, Beelen M, Wallis GA, Gijsen AP, Senden JM, VAN Loon LJ. Protein ingestion before sleep improves postexercise overnight recovery. Med Sci Sports Exerc 44 (8): 1560‐1569, 2012.
 181.Reschke MF, Anderson DJ, Homick JL. Vestibulo‐spinal response modification as determined with the h‐reflex during the spacelab‐1 flight. Exp Brain Res 64 (2): 367‐379, 1986.
 182.Reschke MF, Bloomberg JJ, Harm DL, Paloski WH. Space flight and neurovestibular adaptation. J Clin Pharmacol 34 (6): 609‐617, 1994.
 183.Reschke MF, Bloomberg JJ, Paloski WH, Mulavara AP, Feiveson AH, Harm DL. Postural reflexes, balance control, and functional mobility with long‐duration head‐down bed rest. Aviat Space Environ Med 80 (5 Suppl): A45‐A54, 2009.
 184.Rieu I, Balage M, Sornet C, Giraudet C, Pujos E, Grizard J, Mosoni L, Dardevet D. Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 575 (Pt 1): 305‐315, 2006.
 185.Ritzmann R, Freyler K, Kummel J, Gruber M, Belavy DL, Felsenberg D, Gollhofer A, Kramer A, Ambrecht G. High intensity jump exercise preserves posture control, gait, and functional mobility during 60 days of bed‐rest: An RCT including 90 days of follow‐up. Front Physiol 9: 1713, 2018.
 186.Riva D, Rossitto F, Battocchio L. Postural muscle atrophy prevention and recovery and bone remodelling through high frequency proprioception for astronauts. Acta Astronaut 65 (5‐6): 813‐819, 2009.
 187.Roll JP, Popov K, Gurfinkel V, Lipshits M, Andre‐Deshays C, Gilhodes JC, Quoniam C. Sensorimotor and perceptual function of muscle proprioception in microgravity. J Vestib Res 3 (3): 259‐273, 1993.
 188.Ross H, Brodie E, Benson A. Mass discrimination during prolonged weightlessness. Science 225 (4658): 219‐221, 1984.
 189.Rudnick J, Puttmann B, Tesch PA, Alkner B, Schoser BG, Salanova M, Kirsch K, Gunga HC, Schiffl G, Luck G, Blottner D. 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 (11): 1228‐1230, 2004.
 190.Rummel JA, Sawin CF, Michel EL, Michel MS. Exercise response. In: Johnston RS, Dietlein LF, Berry CA, editors. Biomedical Results of Apollo. Washington, DC: NASA, 1975.
 191.Ruttley TM. The role of body load‐regulating mechanisms in gaze stabilization during locomotion. University of Texas Medical Branch Doctoral Dissertation, 2011.
 192.Ryder JW, Buxton RE, Goetchius E, Scott‐Pandorf M, Hackney KJ, Fiedler J, Ploutz‐Snyder RJ, Bloomberg JJ, Ploutz‐Snyder LL. Influence of muscle strength to weight ratio on functional task performance. Eur J Appl Physiol 113 (4): 911‐921, 2013.
 193.Ryder JW, Fullmer P, Buxton RE, Crowell JB, Goetchius E, Bekdash O, DeWitt JK, Hwang EY, Feiveson A, English KL, Ploutz‐Snyder LL. A novel approach for establishing fitness standards for occupational task performance. Eur J Appl Physiol 119 (7): 1633‐1648, 2019.
 194.Schmitt HH, Reid DJ. Anecdotal Information on Space‐Adaptation Syndrome. Houston, TX: Space Adaptation Syndrome Drug Workshop, 1985.
 195.Schneider SM, Amonette WE, Blazine K, Bentley J, Lee SMC, Loehr JA, Moore AD Jr, Rapley M, Mulder ER, Smith SM. Training with the International Space Station interim resistive exercise device. Med Sci Sports Exerc 35 (11): 1935‐1945, 2003.
 196.Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, Spector E, Feeback DL, Lai D. Resistance exercise as a countermeasure to disuse‐induced bone loss. J Appl Physiol (1985) 97 (1): 119‐129, 2004.
 197.Shenkman BS, Litvinova KS, Nemirovskaya TL, Podlubnaya ZA, Vikhlyantsev IM, Kozlovskaya IB. Afferent and peripheral control of muscle fiber properties during gravitational unloading. J Gravit Physiol 11 (2): P111‐P114, 2004.
 198.Smith SM, Heer MA, Shackelford L, Sibonga JD, Ploutz‐Snyder L, Zwart SR. Benefits for bone from resistance exercise and nutrition in long‐duration spaceflight: Evidence from biochemistry and densitometry. J Bone Miner Res 27 (9): 1896‐1906, 2012.
 199.Smith SM, McCoy T, Gazda D, Morgan JL, Heer M, Zwart SR. Space flight calcium: Implications for astronaut health, spacecraft operations, and earth. Nutrients 4 (12): 2047‐2068, 2012.
 200.Smith SM, Zwart SR, Block G, Rice BL, Davis‐Street JE. The nutritional status of astronauts is altered after long‐term space flight aboard the International Space Station. J Nutr 135 (3): 437‐443, 2005.
 201.Spiering BA, Lee SM, Mulavara AP, Bentley JR, Buxton RE, Lawrence EL, Sinka J, Guilliams ME, Ploutz‐Snyder LL, Bloomberg JJ. Test battery designed to quickly and safely assess diverse indices of neuromuscular function after unweighting. J Strength Cond Res 25 (2): 545‐555, 2011.
 202.Staron RS, Kraemer WJ, Hikida RS, Reed DW, Murray JD, Campos GE, Gordon SE. Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days. Histochem Cell Biol 110 (1): 73‐80, 1998.
 203.Stein TP, Blanc S. Does protein supplementation prevent muscle disuse atrophy and loss of strength? Crit Rev Food Sci Nutr 51 (9): 828‐834, 2011.
 204.Stein TP, Donaldson MR, Leskiw MJ, Schluter MD, Baggett DW, Boden G. Branched‐chain amino acid supplementation during bed rest: Effect on recovery. J Appl Physiol (1985) 94 (4): 1345‐1352, 2003.
 205.Stein TP, Leskiw MJ, Schluter MD, Hoyt RW, Lane HW, Gretebeck RE, LeBlanc AD. Energy expenditure and balance during spaceflight on the space shuttle. Am J Physiol 276 (6 Pt 2): R1739‐R1748, 1999.
 206.Stein TP, Schulter MD, Boden G. Development of insulin resistance by astronauts during spaceflight. Aviat Space Environ Med 65 (12): 1091‐1096, 1994.
 207.Stephens MJ, Yang JF. Loading during the stance phase of walking in humans increases the extensor EMG amplitude but does not change the duration of the step cycle. Exp Brain Res 124 (3): 363‐370, 1999.
 208.Stuart CA, Shangraw RE, Peters EJ, Wolfe RR. Effect of dietary protein on bed‐rest‐related changes in whole‐body‐protein synthesis. Am J Clin Nutr 52 (3): 509‐514, 1990.
 209.Stuart CA, Shangraw RE, Prince MJ, Peters EJ, Wolfe RR. Bed‐rest‐induced insulin resistance occurs primarily in muscle. Metabolism 37 (8): 802‐806, 1988.
 210.Sutterfield SL, Alexander AM, Hammer SM, Didier KD, Caldwell JT, Barstow TJ, Ade CJ. Prediction of planetary mission task performance for long‐duration spaceflight. Med Sci Sports Exerc, 2019.
 211.Suzuki Y, Akima H, Igawa S, Fukunaga T, Kawakub K, Goto S, Makita Y, Gunji A. Decrease of bone mineral density and muscle and/or strength in the leg during 20 days horizontal bed rest. J Gravit Physiol 3 (2): 42‐43, 1996.
 212.Symons TB, Sheffield‐Moore M, Chinkes DL, Ferrando AA, Paddon‐Jones D. Artificial gravity maintains skeletal muscle protein synthesis during 21 days of simulated microgravity. J Appl Physiol (1985) 107 (1): 34‐38, 2009.
 213.Symons TB, Sheffield‐Moore M, Mamerow MM, Wolfe RR, Paddon‐Jones D. The anabolic response to resistance exercise and a protein‐rich meal is not diminished by age. J Nutr Health Aging 15 (5): 376‐381, 2011.
 214.Symons TB, Sheffield‐Moore M, Wolfe RR, Paddon‐Jones D. A moderate serving of high‐quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Diet Assoc 109 (9): 1582‐1586, 2009.
 215.Tabata I, Nishimura K, Kouzaki M, Hirai Y, Ogita F, Miyachi M, Yamamoto K. Effects of moderate‐intensity endurance and high‐intensity intermittent training on anaerobic capacity and VO2max. Med Sci Sports Exerc 28 (10): 1327‐1330, 1996.
 216.Tanner RE, Brunker LB, Agergaard J, Barrows KM, Briggs RA, Kwon OS, Young LM, Hopkins PN, Volpi E, Marcus RL, LaStayo PC, Drummond MJ. Age‐related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation. J Physiol 593 (18): 4259‐4273, 2015.
 217.Tesch PA, Trieschmann JT, Ekberg A. Hypertrophy of chronically unloaded muscle subjected to resistance exercise. J Appl Physiol (1985) 96 (4): 1451‐1458, 2004.
 218.Tesch PA, von Walden F, Gustafsson T, Linnehan RM, Trappe TA. Skeletal muscle proteolysis in response to short‐term unloading in humans. J Appl Physiol (1985) 105 (3): 902‐906, 2008.
 219.Thornton WE, Ord J. Physiological mass measurement in skylab. In: Johnson RS, Dietlein LF, editors. Biomedical Results from Skylab (NASA SP‐377). Washington, DC: U.S. Government Printing Office, 1977, p. 175‐182.
 220.Thornton WE, Rummel JA. Muscular deconditioning and its prevention in space flight. In: Johnson RS, Dietlein LF, editors. Biomedical Results from Skylab (NASA SP‐377). Washington, DC: U.S. Government Printing Office, 1977, p. 191‐197.
 221.Threlkeld AJ, Cooper LD, Monger BP, Craven AN, Haupt HG. Temporospatial and kinematic gait alterations during treadmill walking with body weight suspension. Gait Posture 17 (3): 235‐245, 2003.
 222.Tobin BW, Uchakin PN, Leeper‐Woodford SK. Insulin secretion and sensitivity in space flight: Diabetogenic effects. Nutrition 18 (10): 842‐848, 2002.
 223.Trappe S, Costill D, Gallagher P, Creer A, Peters JR, Evans H, Riley DA, Fitts RH. Exercise in space: Human skeletal muscle after 6 months aboard the International Space Station. J Appl Physiol (1985) 106 (4): 1159‐1168, 2009.
 224.Trappe S, Trappe T, Gallagher P, Harber M, Alkner B, Tesch P. Human single muscle fibre function with 84 day bed‐rest and resistance exercise. J Physiol 557 (Pt 2): 501‐513, 2004.
 225.Trappe SW, Trappe TA, Lee GA, Widrick JJ, Costill DL, Fitts RH. Comparison of a space shuttle flight (sts‐78) and bed rest on human muscle function. J Appl Physiol (1985) 91 (1): 57‐64, 2001.
 226.Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW. 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 (2): 147‐159, 2007.
 227.Virtanen P, Vaananen HK, Pasanen L, Lahde S, Puranen J, Takala TE. Effect of immobilization on carbonic anhydrase iii and myoglobin content in human leg muscle. Acta Physiol Scand 142 (3): 303‐306, 1991.
 228.Wall BT, Hamer HM, de Lange A, Kiskini A, Groen BB, Senden JM, Gijsen AP, Verdijk LB, van Loon LJ. Leucine co‐ingestion improves post‐prandial muscle protein accretion in elderly men. Clin Nutr 32 (3): 412‐419, 2013.
 229.Wall BT, Snijders T, Senden JM, Ottenbros CL, Gijsen AP, Verdijk LB, van Loon LJ. Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men. J Clin Endocrinol Metab 98 (12): 4872‐4881, 2013.
 230.Ward GR, MacDougall JD, Sutton JR, Toews CJ, Jones NL. Activation of human muscle pyruvate dehydrogenase with activity and immobilization. Clin Sci (Lond) 70 (2): 207‐210, 1986.
 231.Watenpaugh DE, Ballard RE, Schneider SM, Lee SM, Ertl AC, William JM, Boda WL, Hutchinson KJ, Hargens AR. Supine lower body negative pressure exercise during bed rest maintains upright exercise capacity. J Appl Physiol (1985) 89 (1): 218‐227, 2000.
 232.Watt DG. Pointing at memorized targets during prolonged microgravity. Aviat Space Environ Med 68 (2): 99‐103, 1997.
 233.Wolfe RR, Miller SL, Miller KB. Optimal protein intake in the elderly. Clin Nutr 27 (5): 675‐684, 2008.
 234.Wood SJ, Loehr JA, Guilliams ME. Sensorimotor reconditioning during and after spaceflight. NeuroRehabilitation 29 (2): 185‐195, 2011.
 235.Wood SJ, Paloski WH, Clark JB. Assessing sensorimotor function following ISS with computerized dynamic posturography. Aerosp Med Hum Perform 86 (12 Suppl): A45‐A53, 2015.
 236.Young LR, Oman CM, Merfeld D, Watt D, Roy S, DeLuca C, Balkwill D, Christie J, Groleau N, Jackson DK, Law G, Modestino S, Mayer W. Spatial orientation and posture during and following weightlessness: Human experiments on spacelab life sciences 1. J Vestib Res 3 (3): 231‐239, 1993.
 237.Zwart SR, Mehta SK, Ploutz‐Snyder R, Bourbeau Y, Locke JP, Pierson DL, Smith SM. Response to vitamin D supplementation during antarctic winter is related to BMI, and supplementation can mitigate Epstein‐Barr virus reactivation. J Nutr 141 (4): 692‐697, 2011.

 

 

 

Teaching Material

Kirk L. English, Jacob J. Bloomberg, Ajitkumar P. Mulavara, Lori L. Ploutz-Snyder. Exercise Countermeasures to Neuromuscular Deconditioning in Spaceflight. Compr Physiol 10: 2020, 171-196.

Didactic Synopsis

Major Teaching Points:

*The mechanical unloading of spaceflight induces significant alterations in the neuromuscular system including decreased muscle mass, muscle strength, muscle power, functional performance, and insulin sensitivity.

*The sensorimotor system also undergoes adaptation during exposure to the microgravity conditions of spaceflight.

*Integrated aerobic and resistance exercise is a potent countermeasure to the degradation of neuromuscular and cardiovascular function and can help in attenuating impairments in functional performance.

*Novel exercise regimens and other strategies are required to mitigate post-flight postural control dysfunction and maintain functional performance.

*Early exercise countermeasures on the International Space Station (ISS) were only partially effective to attenuate physiologic maladaptations due to hardware shortcomings and low intensity exercise protocols.

*In the last 10 y, new exercise hardware and protocols have led to increasingly effective exercise countermeasures and better protection of pre-flight physiologic status.

*Future exploration missions will necessitate smaller, yet equally robust exercise hardware due to smaller vehicles. However, particularly for exploration missions with terrestrial objectives, the physiologic demands on crewmembers will likely be higher than those for ISS crewmembers. As such, in addition to the current emphasis on in-flight exercise countermeasures, greater focus should be placed on pre-flight fitness for duty with a particular emphasis on physiologic preparation for the demands of the mission.

*Aging exacerbates unloading-induced alterations in skeletal muscle, and thus, adjuncts to exercise such as nutritional supplements and testosterone should be considered for optimal physiologic protection.

Didactic Legends

The following legends to the figures that appear throughout the article are written to be useful for teaching.

Figure 1. Teaching Points: The exercise device used on some Apollo missions was based on the Exer-Genie (Exer-Genie, Inc., Fullerton, CA). Within the cylinder, the nylon cords rotate around a shaft, developing controlled resistance. The cords are attached to loop handles. When not in use, the flight device was stored in a cloth bag (inset).

Figure 2. Teaching Points: Ground reaction forces during an iRED squat in 1-g (8).

Figure 3. Teaching Points: Ground reaction forces during a free weight (Smith machine) squat in 1-g (8).

Figure 4. Teaching Points: a) The Advanced Resistive Exercise Device (ARED), pictured on the ground; b) ARED deployed on the International Space Station with a crewmember performing a deadlift.

Figure 5. Teaching Points: The second generation treadmill (T2) on the International Space Station; the crewmember is loaded via a harness and bungee cord system.

Figure 6. Teaching Points: The Cycle Ergometer with Vibration Isolation System (CEVIS) on the International Space Station. The crewmember clips into the pedals via cleated shoes and stabilizes himself using handholds on the frame; there is no seat/saddle.

Figure 7. Teaching Points: Left: Scatter plot of time to complete the course (TCC) for 18 long-duration subjects (6-months exposure to spaceflight) showing a 48% increase in time to traverse the obstacle course one day after landing. Center: Diagram of obstacle course. Right: Recovery of function took an average of 15 days to return to within 95% of their pre-flight level of performance.

Figure 8. Teaching Points: Results from two tests of postural stability (top two rows) along with an assessment of lower body muscle function (bottom row) in long-duration ISS crewmembers (Spaceflight group) and bed rest subjects who performed exercise while in bed (Exercise group) and those that did not exercise (Control group).

Figure 9. Teaching Points: A subset of prominent physiologic systems that are: 1) altered by the microgravity of spaceflight and 2) amenable to protection via exercise countermeasures.  

 

 

 


Related Articles:

Neuromuscular Adaptations to Actual and Simulated Spaceflight
Microgravity Stress: Bone and Connective Tissue
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How to Cite

Kirk L. English, Jacob J. Bloomberg, Ajitkumar P. Mulavara, Lori L. Ploutz‐Snyder. Exercise Countermeasures to Neuromuscular Deconditioning in Spaceflight. Compr Physiol 2019, 10: 171-196. doi: 10.1002/cphy.c190005