Journal Mobile Options
Table of Contents
Vol. 56, No. 2, 2010
Issue release date: March 2010
Free Access
Gerontology 2010;56:157–166
(DOI:10.1159/000252852)

Space, Gravity and the Physiology of Aging: Parallel or Convergent Disciplines? A Mini-Review

Vernikos J.a · Schneider V.S.b
aLife Sciences, NASA and Thirdage llc, Culpeper, Va., bOffice of the Chief Health and Medical Officer and Explorations Systems Mission Directorate, NASA, Washington, D.C., and Uniformed Services University, Bethesda, Md., USA
email Corresponding Author

Abstract

The abnormal physiology that manifests itself in healthy humans during their adaptation to the microgravity of space has all the features of accelerated aging. The mechano-skeletal and vestibulo-neuromuscular stimuli which are below threshold in space, result in an overall greater than 10-fold more rapid onset and time course of muscle and bone atrophy in space and the development of balance and coordination problems on return to Earth than occur with aging. Similarly, the loss of functional capacity of the cardiovascular system that results in space and continuous bed rest is over 10 times faster than in the course of aging. Deconditioning in space from gravity deprivation has brought attention to the medical hazards of deconditioning on Earth from gravity withdrawal as in sedentary aging. Though seemingly reversible after periods of 6 months in space or its ground analog of bed rest, it remains to be seen whether that will be so after longer exposures. Both adaptation to space and aging do not merely parallel but converge as disorders of mechanotransduction. Like spaceflight, its analog bed rest telescopes the changes observed with aging and serves as a useful clinical model for the study of age-related deconditioning. The convergence of the disciplines of aging, along with gravitational and space physiology is advancing the understanding and prevention of modern lifestyle medical disorders.


 goto top of outline Key Words

  • Gravitational physiology
  • Mechanotransduction
  • Accelerated aging models
  • Rehabilitation

 goto top of outline Abstract

The abnormal physiology that manifests itself in healthy humans during their adaptation to the microgravity of space has all the features of accelerated aging. The mechano-skeletal and vestibulo-neuromuscular stimuli which are below threshold in space, result in an overall greater than 10-fold more rapid onset and time course of muscle and bone atrophy in space and the development of balance and coordination problems on return to Earth than occur with aging. Similarly, the loss of functional capacity of the cardiovascular system that results in space and continuous bed rest is over 10 times faster than in the course of aging. Deconditioning in space from gravity deprivation has brought attention to the medical hazards of deconditioning on Earth from gravity withdrawal as in sedentary aging. Though seemingly reversible after periods of 6 months in space or its ground analog of bed rest, it remains to be seen whether that will be so after longer exposures. Both adaptation to space and aging do not merely parallel but converge as disorders of mechanotransduction. Like spaceflight, its analog bed rest telescopes the changes observed with aging and serves as a useful clinical model for the study of age-related deconditioning. The convergence of the disciplines of aging, along with gravitational and space physiology is advancing the understanding and prevention of modern lifestyle medical disorders.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline References
  1. Weinert BT, Timiras PS: Theories of aging. J Appl Physiol 2003;95:1706–1716.
  2. Nicogossian AEN, Huntoon CL, Pool SL: Space Physiology and Medicine. Philadelphia, Lea and Febiger, 1989, 1994.
  3. Nicogossian AE, Parker JF: Space Physiology and Medicine. NASA SP-447, NAS 1.21:447, LC-82-23047. Washington, NASA, 1982.
  4. Dietrick JE, Whedon GD, Shorr E, Toscani V, Davis VB: Effect of immobilization on metabolic and physiologic functions of normal men. Am J Med 1948;4:3–35.
  5. Lutwak L, Whedon GD, Lachance PA, Reid M, Lipscomb H: Mineral, electrolyte and nitrogen balance studies of the GeminiVII fourteen-day orbital space flight. J Clin Endocrinol 1969;29:1140–1156.
  6. Hoffler GW, Johnson RL: Apollo flight crew cardiovascular evaluation; in Johnson RS, Dietlein F (eds): Biomedical Results of Apollo. NASA Special Report SP-368. Washington, NASA, 1975, pp 244–265.
  7. Leach CS, Rambaut PC: Biomedical responses of the Skylab crewmen: an overview. NASA SP-377. Washington, NASA, 1977.
  8. Vernikos J: Human physiology in space. Bioessays 1996;18:1029–1037.
  9. Meck JV, Dreyer SA, Warren LE: Long duration head down bed rest: project overview, vital signs and fluid balance. Aviat Space Environ Med 2009;80(suppl 5):1–8.

    External Resources

  10. Pavy-Le Traon A, Heer M, Naric MV, Rittweger J, Vernikos J: From space to earth: advances in human physiology from 20 years of bed rest studies (1986–2006) Eur J Appl Physiol 2007;101:143–194.
  11. Sandler H, Vernikos J (eds): Inactivity: physiological effects. New York, Academic Press, 1986.
  12. With the Passage of Time: The Baltimore Longitudinal Study of Aging. October 1993. National Institute on Aging, National Institutes of Health, Bethesda, Maryland. www.nia.nih.gov/HealthInformation/Publications/BLSA/01_why.htm.
  13. Pierson DL, Mehta SK, Stowe RP: Reactivation of latent herpes viruses in astronauts; in Ader R: Psychoneuroimmunology, ed 4. Amsterdam, Elsevier, vol 1, chapter 40, pp 851–868, 2008.
  14. Wilson JW, Ott CM, Quick L, et al: Media ion composition controls regulatory and virulence response of Salmonella in spaceflight. PLoS One 2008;3:3923.

    External Resources

  15. Mulvaugh, SL, Charles JB, Riddle JM, Rehbein TL, Bungo MW: Echocardiographic evaluation of the cardiovascular effects of short-duration spaceflight. J Clin Pharmacol 1991;31:1024–1026.
  16. Levine BD, Lane LD, Watenpaugh DE, Gaffney FA, Buckey JC, Blomquist CG: Maximal exercise performance after adaptation to microgravity. J Appl Physiol 1996;81:686–694.
  17. Levine BD, Pawelczyk JA, Ertl AC, Cox JF, Zuckerman JH, Diedrich A, Biaggioni I: Human muscle sympathetic neural and hemodynamic responses to tilt following spaceflight. J Physiol 2002;538:331–334.
  18. Convertino VA: Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures. J Gravit Physiol 2002;9:1–13.

    External Resources

  19. Pawelczyk JA, Zuckerman JH, Blomquist CG, Levine BD: Regulation of muscle sympathetic nerve activity after bed rest deconditioning. Am J Physiol Heart Circ Physiol 2001;280:2230–2239.
  20. Iwasaki K-I, Zhang R, Perhonen MA, Zuckerman JH, Levine BD: Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration. Am J Physiol Regul Integr Comp Physiol 2004;287:1256–1262.
  21. Ferrari AU, Radaeli A, Cantola M: Aging and the cardiovascular system. J Appl Physiol 2003;95:2591–2597.
  22. McGavock JM, Hastings, Snell PG, McGuire DK, Pacini EL, Levine BD, Mitchell JH: A forty-year follow-up of the Dallas bed rest and training study: the effect of age on the cardiovascular response to exercise in men. J Gerontol A Biol Sci Med Sci 2009;64:293–299.
  23. Perhonen MA, Franco F, Lane LD, Buckey JC, Blomquist CG, Zerwe KH JE, Peshok RM, Weatherall PT, Levine BD: Cardiac atrophy after bed-rest and space flight. J Appl Physiol 2001;91:645–653.
  24. Prasad A, Popovic ZB, Arbali-Zadeh A, et al: The effects of aging and physical activity on Doppler measures of diastolic function. Am J Cardiol 2007;99:1629–1636.
  25. Prasad A, Levine BD: Aging and diastolic heart failure; in Klein A, Garcia M (eds): A Clinical Approach to Diastolic Heart Failure. St. Louis, GW Medical Publishing, 2008, chapter 30, pp 385–400.
  26. Muller-Delp JM, Spiers SA, Ramsey MW, Delp MD: Aging impairs endothelium-dependent vasodilation in rat skeletal muscle arterioles. Am J Physiol Heat Circ Phys 2002;283:1662–1672.
  27. Delp MD: Arterial adaptations in microgravity contribute to orthostatic tolerance. J Appl Physiol 2007;102:836.
  28. Arbab-Zadeh A, Dijk E, Prasad A, et al: Effect of aging and physical activity on left ventricular compliance. Circulation 2004;110:1799–1805.
  29. Di Prampero PE, Narici MV: Muscles in space; in Fitton B, Battrick B (eds): A World without Gravity. ESA SP-1251. Noordwijk, European Space Agency, 2001, pp 69–82.
  30. Fleg JL, Shapiro EP, O’Connor F, et al: Left ventricular diastolic filling performance in older male athletes. JAMA 1995:273:1371–1375.
  31. Tesch PA, Berg HE, Bring D, Evans HJ, LeBlanc AD: Effects of 17 day spaceflight on knee extensor muscle function and size. Eur J Appl Physiol 2005;94:463–468.

    External Resources

  32. 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 1992,73:2172–2178.
  33. Schild HH, Heller M (eds): Osteoporose. Stuttgart, Georg Thieme, 1992.
  34. Janz KF, Medema-Johnson HC, Letuchy EM, Burns TL, Gilmore JM, Torner JC, Willing M, Levy SM: Subjective and objective measures of physical activity in relationship to bone mineral content during late childhood: the Iowa Bone Development Study. Br J Sports Med 2008;42:658–663.
  35. LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, Voronin L: Bone mineral and lean tissue loss after long duration space flight. J Musculoskelet Neuronal Interact 2000;1:157–160.
  36. Keyak JH, Koyama, AK, LeBlanc A, Lu Y, Lang TF: Reduction in proximal femoral strength due to long-duration spaceflight. Bone 2009;44:449–453.
  37. Sibonga JD, Cavanagh PR, Lang TF, LeBlanc AD, Schneider VS, Shackelford LC, Smith SM, Vico: Adaptation of the skeletal system during long-duration spaceflight. Clin Rev Bone Miner Metab 2007;5:249–261.

    External Resources

  38. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A: Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 2004;19:1006–1012.
  39. Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, et al: Effects of a 120-day period of bed-rest on bone mass and bone cell activities in man: attempts at countermeasures. Bone Miner 1987;2:383–394.
  40. Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM: Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res 1990;5:843–850.
  41. Rittweger J, Felsenberg D: Recovery of muscle atrophy and bone loss from 90 days bed rest: results from a one-year follow-up. Bone 2009;44:214–224.
  42. Warden SJ, Fuchs RK: Exercise and bone health: optimizing structure during growth is key, but all is not in vain during aging. Br J Sports Med DOI:10.1136/bjsm.2008. 054866.

    External Resources

  43. Bacabac, RG, Smit TH, Mullender MG, Dijcks SJ, van Loon JJWA: Klein-Nulend J: Nitric oxide production by bone cells is fluid shear stress rate dependent. Biochem Biophys Res Commun 2004;315:823–829.
  44. Van Loon JJWA: Microgravity and mechanomics. Gravit Space Biol Bull 2007;20:3–18.
  45. Rubin C, Turner AS, Muller R, Mittra E, McLeod K, Lin W, Qin YX: Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J Bone Miner Res 2002;17:349–357.
  46. Adams GR, Caiozzo VJ, Baldwin KM: Skeletal muscle unweighting: spaceflight and ground-based models J Appl Physiol 2003;95:2185–2201.
  47. Lynch GS: Update on emerging drugs for sarcopenia – age-related muscle wasting. Expert Opin Emerg Drugs 2008;14:655–673.

    External Resources

  48. Vernikos J: The G-Connection: Harness Gravity and Reverse Aging. Lincoln, iUniverse, 2004.
  49. Trappe S, Costill D, Gallagher PM, 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 2009;106:1159–1168.
  50. Bachl N, Baron R, Tschan H, Mossaheb M, Bumba W, Hildebrand F, Knauf M, Witt M, Albrecht R, Kozlovskaya I, et al: Principles of muscle efficiency in weightlessness (in German). Wien Med Wochenschr 1993,143:588–610.
  51. LeBlanc A, Rowe R, Schneider V, Evans H, Hedrick T: Regional muscle loss after short duration spaceflight. Aviat Space Environ Med 1995;66:1151–1154.
  52. Snijders T, Verdijk LB, van Loon LJ: The impact of sarcopenia and exercise training on skeletal muscle satellite cells. Ageing Res Rev 2009;8:328–338.
  53. Booth FW, Chakravathy MV, Spangenberg EE: Exercise and gene expression: physiological regulation of the human genome through physical activity J Physiol 2002;543:399–411.
  54. Chakrovarthy MV, Booth FW: Eating, exercise and ‘thrifty’ genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 2004,96:3–10.
  55. 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 1990;52:509–514.
  56. Biolo G, Ciocchi B, Lebenstedt M, Barazzoni R, Zanetti M, Platen P, Heer M, Guarnieri G: Short-term bed rest impairs amino-acid- induced protein anabolism in humans. J Physiol 2004;558:381–388.
  57. 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 2000;89:2158–2164.
  58. Krebs JM, Schneider VS, Evans H, Kuo MC, LeBlanc AD: Energy absorption, lean body mass, and total body fat changes during 5 weeks of continuous bed rest. Aviat Space Environ Med 1990;61:314–318.
  59. LeRoith D: Dyslipidemia and glucose dysregulation in overweight and obese patients. Clin Cornerstone 2007;8:38–52.
  60. Mikines KJ, Richter EA, Dela F, Galbo H: Seven days of bed rest on dose-response relation between plasma glucose and insulin action on glucose uptake in leg and whole body. J Appl Physiol 1991;70:1245–1254.
  61. Rubin CT, Capilla E, Luu YK, Busa B, Ceawford H, Nolan DJ, Mittal V, Rosen CJ, Pessin JE, Judex S: Adipogenesis is inhibited by brief, daily exposure to high frequency, extremely low-magnitude mechanical signals. PNAS 2007;104:17879–17884.
  62. 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 2005;135:437–443.
  63. Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA, Davis-Street JE, Oganov V, Shackelford LC: Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir space station. J Bone Miner Res 2005;20:208–218.
  64. Gerzer R, Heer M: Regulation of body fluid and salt homeostasis – from observations in space to new concepts on Earth. Curr Pharm Biotechnol 2005;6:299–304.
  65. Leach CS, Johnson PC, Cintrón NM: The endocrine system in space flight. Acta Astronaut 1988;17:161–166.
  66. Pietrzyk RA, Jones JA, Sams CF, Whitson PA: Renal stone formation among astronauts. Aviat Space Environ Med 2007;78(4 suppl):9–13.
  67. Horak FB: Adaptation for automatic postural responses; in Bloedel J, Ebner J, Wise S (eds): The Acquisition of Motor Behavior in Vertebrates. Cambridge, MIT Press, chapter 4, 1996.
  68. 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 2009;80(5 suppl):45–54.

    External Resources

  69. 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 1993;14:9–17.
  70. Paloski WH, Black FO, Metter EJ: Postflight balance control recovery in an elderly astronaut: a case report. Otol Neurotol 2004;25:53–56.
  71. Feiveson AH, Metter EJ, Paloski WH: A statistical model for interpreting computerized dynamic posturography data. IEEE Trans Biomed Eng 2002;49:300–309.
  72. Dijk DJ, Neri DF, Wyatt JK, Ronda JM, Riel E, Ritz-De Cecco A, Hughes RT, Elliott AR, Prisk GK, West JB: Sleep, performance, circadian rhythms and light-dark cycles during two space shuttle flights. Am J Physiol 2001;281:1647–1664.
  73. Winget CM, Vernikos-Danellis J, Cronin S, Leach CS, Rambaut PC, Mack PB: Circadian rhythm asynchrony in humans during hypokinesis. J Appl Physiol 1972;33:640–645.
  74. Monk TH, Kennedy SK, Rose LR, Linenger JM: Decreased human circadian pacemaker influence after 100 days in space: a case study. Psychosom Med 2001;63:881–885.
  75. Silver FH, DeVore D, Siperko LM: Role of mechanophysiology in aging of ECM: effects of changes in mechanochemical transduction. J Appl Physiol 2003;95:2134–2141.
  76. Ingber DE: Tensegrity-based mechanosensing from macro to micro. Prog Biophys Mol Biol 2008;97:163–179.
  77. Pietramaggiori G, Liu P, Scherer SS, Kaipanen A, Prsa MJ, Mayer H, Newalder J, Alperovich M, Mentzer SJ, Konerding MA, Huang S, Ingber DE, Orgill DP: Tensile forces stimulate vascular remodeling and epidermal cell proliferation in living skin. Ann Surg 2007;246:896–902.

 goto top of outline Author Contacts

Dr. Joan Vernikos
Thirdage llc
2028 Golf Drive
Culpeper, VA 22701 (USA)
Tel. +1 540 829 2541, E-Mail dr.joan@joanvernikos.com


 goto top of outline Article Information

Received: April 17, 2009
Accepted: August 27, 2009
Published online: October 23, 2009
Number of Print Pages : 10
Number of Figures : 0, Number of Tables : 0, Number of References : 77


 goto top of outline Publication Details

Gerontology (International Journal of Experimental, Clinical, Behavioural and Technological Gerontology)

Vol. 56, No. 2, Year 2010 (Cover Date: March 2010)

Journal Editor: Wick G. (Innsbruck)
ISSN: 0304-324X (Print), eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

The abnormal physiology that manifests itself in healthy humans during their adaptation to the microgravity of space has all the features of accelerated aging. The mechano-skeletal and vestibulo-neuromuscular stimuli which are below threshold in space, result in an overall greater than 10-fold more rapid onset and time course of muscle and bone atrophy in space and the development of balance and coordination problems on return to Earth than occur with aging. Similarly, the loss of functional capacity of the cardiovascular system that results in space and continuous bed rest is over 10 times faster than in the course of aging. Deconditioning in space from gravity deprivation has brought attention to the medical hazards of deconditioning on Earth from gravity withdrawal as in sedentary aging. Though seemingly reversible after periods of 6 months in space or its ground analog of bed rest, it remains to be seen whether that will be so after longer exposures. Both adaptation to space and aging do not merely parallel but converge as disorders of mechanotransduction. Like spaceflight, its analog bed rest telescopes the changes observed with aging and serves as a useful clinical model for the study of age-related deconditioning. The convergence of the disciplines of aging, along with gravitational and space physiology is advancing the understanding and prevention of modern lifestyle medical disorders.



 goto top of outline Author Contacts

Dr. Joan Vernikos
Thirdage llc
2028 Golf Drive
Culpeper, VA 22701 (USA)
Tel. +1 540 829 2541, E-Mail dr.joan@joanvernikos.com


 goto top of outline Article Information

Received: April 17, 2009
Accepted: August 27, 2009
Published online: October 23, 2009
Number of Print Pages : 10
Number of Figures : 0, Number of Tables : 0, Number of References : 77


 goto top of outline Publication Details

Gerontology (International Journal of Experimental, Clinical, Behavioural and Technological Gerontology)

Vol. 56, No. 2, Year 2010 (Cover Date: March 2010)

Journal Editor: Wick G. (Innsbruck)
ISSN: 0304-324X (Print), eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Weinert BT, Timiras PS: Theories of aging. J Appl Physiol 2003;95:1706–1716.
  2. Nicogossian AEN, Huntoon CL, Pool SL: Space Physiology and Medicine. Philadelphia, Lea and Febiger, 1989, 1994.
  3. Nicogossian AE, Parker JF: Space Physiology and Medicine. NASA SP-447, NAS 1.21:447, LC-82-23047. Washington, NASA, 1982.
  4. Dietrick JE, Whedon GD, Shorr E, Toscani V, Davis VB: Effect of immobilization on metabolic and physiologic functions of normal men. Am J Med 1948;4:3–35.
  5. Lutwak L, Whedon GD, Lachance PA, Reid M, Lipscomb H: Mineral, electrolyte and nitrogen balance studies of the GeminiVII fourteen-day orbital space flight. J Clin Endocrinol 1969;29:1140–1156.
  6. Hoffler GW, Johnson RL: Apollo flight crew cardiovascular evaluation; in Johnson RS, Dietlein F (eds): Biomedical Results of Apollo. NASA Special Report SP-368. Washington, NASA, 1975, pp 244–265.
  7. Leach CS, Rambaut PC: Biomedical responses of the Skylab crewmen: an overview. NASA SP-377. Washington, NASA, 1977.
  8. Vernikos J: Human physiology in space. Bioessays 1996;18:1029–1037.
  9. Meck JV, Dreyer SA, Warren LE: Long duration head down bed rest: project overview, vital signs and fluid balance. Aviat Space Environ Med 2009;80(suppl 5):1–8.

    External Resources

  10. Pavy-Le Traon A, Heer M, Naric MV, Rittweger J, Vernikos J: From space to earth: advances in human physiology from 20 years of bed rest studies (1986–2006) Eur J Appl Physiol 2007;101:143–194.
  11. Sandler H, Vernikos J (eds): Inactivity: physiological effects. New York, Academic Press, 1986.
  12. With the Passage of Time: The Baltimore Longitudinal Study of Aging. October 1993. National Institute on Aging, National Institutes of Health, Bethesda, Maryland. www.nia.nih.gov/HealthInformation/Publications/BLSA/01_why.htm.
  13. Pierson DL, Mehta SK, Stowe RP: Reactivation of latent herpes viruses in astronauts; in Ader R: Psychoneuroimmunology, ed 4. Amsterdam, Elsevier, vol 1, chapter 40, pp 851–868, 2008.
  14. Wilson JW, Ott CM, Quick L, et al: Media ion composition controls regulatory and virulence response of Salmonella in spaceflight. PLoS One 2008;3:3923.

    External Resources

  15. Mulvaugh, SL, Charles JB, Riddle JM, Rehbein TL, Bungo MW: Echocardiographic evaluation of the cardiovascular effects of short-duration spaceflight. J Clin Pharmacol 1991;31:1024–1026.
  16. Levine BD, Lane LD, Watenpaugh DE, Gaffney FA, Buckey JC, Blomquist CG: Maximal exercise performance after adaptation to microgravity. J Appl Physiol 1996;81:686–694.
  17. Levine BD, Pawelczyk JA, Ertl AC, Cox JF, Zuckerman JH, Diedrich A, Biaggioni I: Human muscle sympathetic neural and hemodynamic responses to tilt following spaceflight. J Physiol 2002;538:331–334.
  18. Convertino VA: Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures. J Gravit Physiol 2002;9:1–13.

    External Resources

  19. Pawelczyk JA, Zuckerman JH, Blomquist CG, Levine BD: Regulation of muscle sympathetic nerve activity after bed rest deconditioning. Am J Physiol Heart Circ Physiol 2001;280:2230–2239.
  20. Iwasaki K-I, Zhang R, Perhonen MA, Zuckerman JH, Levine BD: Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration. Am J Physiol Regul Integr Comp Physiol 2004;287:1256–1262.
  21. Ferrari AU, Radaeli A, Cantola M: Aging and the cardiovascular system. J Appl Physiol 2003;95:2591–2597.
  22. McGavock JM, Hastings, Snell PG, McGuire DK, Pacini EL, Levine BD, Mitchell JH: A forty-year follow-up of the Dallas bed rest and training study: the effect of age on the cardiovascular response to exercise in men. J Gerontol A Biol Sci Med Sci 2009;64:293–299.
  23. Perhonen MA, Franco F, Lane LD, Buckey JC, Blomquist CG, Zerwe KH JE, Peshok RM, Weatherall PT, Levine BD: Cardiac atrophy after bed-rest and space flight. J Appl Physiol 2001;91:645–653.
  24. Prasad A, Popovic ZB, Arbali-Zadeh A, et al: The effects of aging and physical activity on Doppler measures of diastolic function. Am J Cardiol 2007;99:1629–1636.
  25. Prasad A, Levine BD: Aging and diastolic heart failure; in Klein A, Garcia M (eds): A Clinical Approach to Diastolic Heart Failure. St. Louis, GW Medical Publishing, 2008, chapter 30, pp 385–400.
  26. Muller-Delp JM, Spiers SA, Ramsey MW, Delp MD: Aging impairs endothelium-dependent vasodilation in rat skeletal muscle arterioles. Am J Physiol Heat Circ Phys 2002;283:1662–1672.
  27. Delp MD: Arterial adaptations in microgravity contribute to orthostatic tolerance. J Appl Physiol 2007;102:836.
  28. Arbab-Zadeh A, Dijk E, Prasad A, et al: Effect of aging and physical activity on left ventricular compliance. Circulation 2004;110:1799–1805.
  29. Di Prampero PE, Narici MV: Muscles in space; in Fitton B, Battrick B (eds): A World without Gravity. ESA SP-1251. Noordwijk, European Space Agency, 2001, pp 69–82.
  30. Fleg JL, Shapiro EP, O’Connor F, et al: Left ventricular diastolic filling performance in older male athletes. JAMA 1995:273:1371–1375.
  31. Tesch PA, Berg HE, Bring D, Evans HJ, LeBlanc AD: Effects of 17 day spaceflight on knee extensor muscle function and size. Eur J Appl Physiol 2005;94:463–468.

    External Resources

  32. 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 1992,73:2172–2178.
  33. Schild HH, Heller M (eds): Osteoporose. Stuttgart, Georg Thieme, 1992.
  34. Janz KF, Medema-Johnson HC, Letuchy EM, Burns TL, Gilmore JM, Torner JC, Willing M, Levy SM: Subjective and objective measures of physical activity in relationship to bone mineral content during late childhood: the Iowa Bone Development Study. Br J Sports Med 2008;42:658–663.
  35. LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, Voronin L: Bone mineral and lean tissue loss after long duration space flight. J Musculoskelet Neuronal Interact 2000;1:157–160.
  36. Keyak JH, Koyama, AK, LeBlanc A, Lu Y, Lang TF: Reduction in proximal femoral strength due to long-duration spaceflight. Bone 2009;44:449–453.
  37. Sibonga JD, Cavanagh PR, Lang TF, LeBlanc AD, Schneider VS, Shackelford LC, Smith SM, Vico: Adaptation of the skeletal system during long-duration spaceflight. Clin Rev Bone Miner Metab 2007;5:249–261.

    External Resources

  38. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A: Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 2004;19:1006–1012.
  39. Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, et al: Effects of a 120-day period of bed-rest on bone mass and bone cell activities in man: attempts at countermeasures. Bone Miner 1987;2:383–394.
  40. Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM: Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res 1990;5:843–850.
  41. Rittweger J, Felsenberg D: Recovery of muscle atrophy and bone loss from 90 days bed rest: results from a one-year follow-up. Bone 2009;44:214–224.
  42. Warden SJ, Fuchs RK: Exercise and bone health: optimizing structure during growth is key, but all is not in vain during aging. Br J Sports Med DOI:10.1136/bjsm.2008. 054866.

    External Resources

  43. Bacabac, RG, Smit TH, Mullender MG, Dijcks SJ, van Loon JJWA: Klein-Nulend J: Nitric oxide production by bone cells is fluid shear stress rate dependent. Biochem Biophys Res Commun 2004;315:823–829.
  44. Van Loon JJWA: Microgravity and mechanomics. Gravit Space Biol Bull 2007;20:3–18.
  45. Rubin C, Turner AS, Muller R, Mittra E, McLeod K, Lin W, Qin YX: Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J Bone Miner Res 2002;17:349–357.
  46. Adams GR, Caiozzo VJ, Baldwin KM: Skeletal muscle unweighting: spaceflight and ground-based models J Appl Physiol 2003;95:2185–2201.
  47. Lynch GS: Update on emerging drugs for sarcopenia – age-related muscle wasting. Expert Opin Emerg Drugs 2008;14:655–673.

    External Resources

  48. Vernikos J: The G-Connection: Harness Gravity and Reverse Aging. Lincoln, iUniverse, 2004.
  49. Trappe S, Costill D, Gallagher PM, 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 2009;106:1159–1168.
  50. Bachl N, Baron R, Tschan H, Mossaheb M, Bumba W, Hildebrand F, Knauf M, Witt M, Albrecht R, Kozlovskaya I, et al: Principles of muscle efficiency in weightlessness (in German). Wien Med Wochenschr 1993,143:588–610.
  51. LeBlanc A, Rowe R, Schneider V, Evans H, Hedrick T: Regional muscle loss after short duration spaceflight. Aviat Space Environ Med 1995;66:1151–1154.
  52. Snijders T, Verdijk LB, van Loon LJ: The impact of sarcopenia and exercise training on skeletal muscle satellite cells. Ageing Res Rev 2009;8:328–338.
  53. Booth FW, Chakravathy MV, Spangenberg EE: Exercise and gene expression: physiological regulation of the human genome through physical activity J Physiol 2002;543:399–411.
  54. Chakrovarthy MV, Booth FW: Eating, exercise and ‘thrifty’ genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 2004,96:3–10.
  55. 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 1990;52:509–514.
  56. Biolo G, Ciocchi B, Lebenstedt M, Barazzoni R, Zanetti M, Platen P, Heer M, Guarnieri G: Short-term bed rest impairs amino-acid- induced protein anabolism in humans. J Physiol 2004;558:381–388.
  57. 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 2000;89:2158–2164.
  58. Krebs JM, Schneider VS, Evans H, Kuo MC, LeBlanc AD: Energy absorption, lean body mass, and total body fat changes during 5 weeks of continuous bed rest. Aviat Space Environ Med 1990;61:314–318.
  59. LeRoith D: Dyslipidemia and glucose dysregulation in overweight and obese patients. Clin Cornerstone 2007;8:38–52.
  60. Mikines KJ, Richter EA, Dela F, Galbo H: Seven days of bed rest on dose-response relation between plasma glucose and insulin action on glucose uptake in leg and whole body. J Appl Physiol 1991;70:1245–1254.
  61. Rubin CT, Capilla E, Luu YK, Busa B, Ceawford H, Nolan DJ, Mittal V, Rosen CJ, Pessin JE, Judex S: Adipogenesis is inhibited by brief, daily exposure to high frequency, extremely low-magnitude mechanical signals. PNAS 2007;104:17879–17884.
  62. 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 2005;135:437–443.
  63. Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA, Davis-Street JE, Oganov V, Shackelford LC: Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir space station. J Bone Miner Res 2005;20:208–218.
  64. Gerzer R, Heer M: Regulation of body fluid and salt homeostasis – from observations in space to new concepts on Earth. Curr Pharm Biotechnol 2005;6:299–304.
  65. Leach CS, Johnson PC, Cintrón NM: The endocrine system in space flight. Acta Astronaut 1988;17:161–166.
  66. Pietrzyk RA, Jones JA, Sams CF, Whitson PA: Renal stone formation among astronauts. Aviat Space Environ Med 2007;78(4 suppl):9–13.
  67. Horak FB: Adaptation for automatic postural responses; in Bloedel J, Ebner J, Wise S (eds): The Acquisition of Motor Behavior in Vertebrates. Cambridge, MIT Press, chapter 4, 1996.
  68. 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 2009;80(5 suppl):45–54.

    External Resources

  69. 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 1993;14:9–17.
  70. Paloski WH, Black FO, Metter EJ: Postflight balance control recovery in an elderly astronaut: a case report. Otol Neurotol 2004;25:53–56.
  71. Feiveson AH, Metter EJ, Paloski WH: A statistical model for interpreting computerized dynamic posturography data. IEEE Trans Biomed Eng 2002;49:300–309.
  72. Dijk DJ, Neri DF, Wyatt JK, Ronda JM, Riel E, Ritz-De Cecco A, Hughes RT, Elliott AR, Prisk GK, West JB: Sleep, performance, circadian rhythms and light-dark cycles during two space shuttle flights. Am J Physiol 2001;281:1647–1664.
  73. Winget CM, Vernikos-Danellis J, Cronin S, Leach CS, Rambaut PC, Mack PB: Circadian rhythm asynchrony in humans during hypokinesis. J Appl Physiol 1972;33:640–645.
  74. Monk TH, Kennedy SK, Rose LR, Linenger JM: Decreased human circadian pacemaker influence after 100 days in space: a case study. Psychosom Med 2001;63:881–885.
  75. Silver FH, DeVore D, Siperko LM: Role of mechanophysiology in aging of ECM: effects of changes in mechanochemical transduction. J Appl Physiol 2003;95:2134–2141.
  76. Ingber DE: Tensegrity-based mechanosensing from macro to micro. Prog Biophys Mol Biol 2008;97:163–179.
  77. Pietramaggiori G, Liu P, Scherer SS, Kaipanen A, Prsa MJ, Mayer H, Newalder J, Alperovich M, Mentzer SJ, Konerding MA, Huang S, Ingber DE, Orgill DP: Tensile forces stimulate vascular remodeling and epidermal cell proliferation in living skin. Ann Surg 2007;246:896–902.