Volume 41 Issue 1
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GUO Jinhu, GAN Xihui, MA Huan. Time in Space:Advances in the Study of Circadian Rhythms under Microgravity[J]. Journal of Space Science, 2021, 41(1): 145-157. doi: 10.11728/cjss2021.01.145
Citation: GUO Jinhu, GAN Xihui, MA Huan. Time in Space:Advances in the Study of Circadian Rhythms under Microgravity[J]. Journal of Space Science, 2021, 41(1): 145-157. doi: 10.11728/cjss2021.01.145

Time in Space:Advances in the Study of Circadian Rhythms under Microgravity

doi: 10.11728/cjss2021.01.145
  • Received Date: 2020-11-06
  • Publish Date: 2021-01-15
  • Circadian clocks, derived from long-term evolution, are endogenous mechanisms which endow the organisms to adapt to the daily cycling environment on Earth. At the molecular level, circadian clocks are controlled by a series of clock genes and other clock associated regulators. At the tissue level, circadian systems are composed of master and peripheral clocks. Circadian clocks affect physiology, cognition and behavior of almost all organisms, which dictate their adaptability to the environment. Space environmental factors, e.g., microgravity, radiation, lighting condition and social factors, dramatically differ from those on the Earth, which may lead to impacts on circadian rhythms. Therefore, circadian clock needs to be considered in the study of space life sciences. Misalignment in circadian rhythms leads to sleep disorder and affects the skeleton-muscular system, neural system, cardio-vascular system, endocrine system, and so on, and decreases the performance of astronauts. Circadian clock will be a critical factor in future space life research and in study of astronaut health and performance.


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  • [1]
    ZWART S R, GIBSON C R, MADER T H, et al. Vision changes after spaceflight are related to alterations in folate-and vitamin B-12-dependent one-carbon metabolism[J]. J. Nutr., 2012, 142(3):427-431
    BRADDOCK M. Ergonomic challenges for astronauts during space travel and the need for space medicine[J]. J. Ergon., 2017, 7(221):2
    CONVERTINO V A. Status of cardiovascular issues related to space flight:implications for future research directions[J]. Respir. Physiol. Neurobiol., 2009, 169:34-37
    MISHRA B, LUDERER U. Reproductive hazards of space travel in women and men[J]. Nat. Rev. Endocrinol., 2019, 15(12):713-730
    GUO Jinhu, QU Weimin, TIAN Yu. Biological Rhythms and Behavior[M]. Beijing:National Defense Industry Press, 2019(郭金虎, 曲卫敏, 田雨. 生物节律与行为[M]. 北京:国防工业出版社, 2019)
    CHEN Shanguang. Manned Space Technology[M]. Beijing:China Astronautic Publishing House, 2018(陈善广. 载人航天技术[M]. 北京:中国宇航出版社, 2018)
    LIANG X, ZHANG L, SHEN H, et al. Effects of a 45-day head-down bed rest on the diurnal rhythms of activity, sleep, and heart rate[J]. Biol. Rhythm. Res., 2014, 45(4):591-601
    GUO J H, QU W M, CHEN S G, et al. Keeping the right time in space:importance of circadian clock and sleep for physiology and performance of astronauts[J]. Mil. Med. Res., 2014, 1:23
    GARRETT-BAKELMAN F E, DARSHI M, GREEN S J, et al. The NASA Twins Study:a multidimensional analysis of a year-long human spaceflight[J]. Science, 2019, 364(6436):8650
    BELL-PEDERSEN D, CASSONE V M, EARNEST D J, et al. Circadian rhythms from multiple oscillators:lessons from diverse organisms[J]. Nat. Rev. Genet., 2005, 6(7):544-556
    GUO J H, MA X H, MA H, et al. Circadian misalignment on submarines and other non-24-h environments——from research to application[J]. Mil. Med. Res., 2020, 7(1):1-12
    KUSAKINA J, DODD A N. Phosphorylation in the plant circadian system[J]. Trends. Plant. Sci., 2012, 17(10):575-583
    HUANG W, RAMSEY K M, MARCHEVA B, et al. Circadian rhythms, sleep, and metabolism[J]. J. Clin. Invest., 2011, 121(6):2133-2141
    TAKAHASHI J S. Transcriptional architecture of the mammalian circadian clock[J]. Nat. Rev. Genet., 2017, 18(3):164
    FRAIKIN G Y, STRAKHOVSKAYA M G, RUBIN A B. Biological photoreceptors of light-dependent regulatory processes[J]. Biochemistry, 2013, 78(11):1238-1253
    KO C H, TAKAHASHI J S. Molecular components of the mammalian circadian clock[J]. Human Mol. Genet., 2006, 15:271-277
    SOLT L A, KPJETIN D J, BURRIS T P. The REV-ERBs and RORs:molecular links between circadian rhythms and lipid homeostasis[J]. Future Med. Chem., 2011, 3:623-638
    UEYAMA T, KROUT K E, VAN NGUYEN X, et al. Suprachiasmatic nucleus:a central autonomic clock[J]. Nat. Neurosci., 1999, 2(12):1051-1053
    BUTLER M P, RAINBOW M N, RODRIGUEZ E, et al. Twelve-hour days in the brain and behavior of split hamsters[J]. Eur. J. Neurosci., 2012, 36(4):2556-2566
    ANTLE M C, SILVER R. Orchestrating time:arrangements of the brain circadian clock[J]. Trends. Neurosci., 2005, 28(3):145-151
    DE PAULA R M, LAMB T M, BENNETT L, et al. A connection between MAPK pathways and circadian clocks[J]. Cell Cycle, 2008, 7(17):2630-2634
    GONCALVES C F, MENG Q J. Timing metabolism in cartilage and bone:links between circadian clocks and tissue homeostasis[J]. J. Endocrinol., 2019, 243(3):29-46
    KARATSOREOS I N. Effects of circadian disruption on mental and physical health[J]. Curr. Neurol. Neurosci. Rep., 2012, 12(2):218-225
    BECHTOLD D A, GIBBS J E, LOUNDON A S I. Circadian dysfunction in disease[J]. Trends. Pharmacol. Sci., 2010, 31(5):191-198
    QIN Ximing, GUO Jinhu. Synchronization of the mammalian central and peripheral circadian clocks[J]. Chin. Sci. Bull., 2017, 62:2849-2856(秦曦明, 郭金虎. 哺乳动物生物钟同步化的研究进展[J]. 科学通报, 2017, 62(25):2849-2856)
    WANG D, ZHANG L, LIANG X, et al. Space meets time:impact of gravity on circadian/diurnal rhythms[J]. Spons. Suppl. Sci.:Human Perform. Space-Adv. Astronaut. Res. China, 2014, 15:17
    NIKAIDO S S, JOHNSON C H. Daily and circadian variation in survival from ultraviolet radiation in Chlamydomonas reinhardtii[J]. Photochem. Photobiol., 2000, 71:758-765
    PITTENDRIGH C S, MINIS D H. Circadian systems:longevity as a function of circadian resonance in Drosophila melanogaster[J]. Proc. Natl. Acad. Sci. USA., 1972, 69:1537-1539
    NSA I Y, KARUNARATHNA N, LIU X, et al. A novel cryptochrome-dependent oscillator in Neurospora crassa[J]. Genetics, 2005, 199(1):233-245
    SPOELSTRA S L, GIVEN C W, SIKORSKII A, et al. A randomized controlled trial of the feasibility and preliminary efficacy of a texting intervention on medication adherence in adults prescribed oral anti-cancer agents:study protocol[J]. J. Adv. Nurs., 2015, 71(12):2965-2976
    SPOELSTRA K, WIKELSKI M, DAAN S, et al. Natural selection against a circadian clock gene mutation in mice[J]. Proc. Natl. Acad. Sci. USA., 2016, 113(3):686-691
    DECOURSEY P J, KRULAS J R. Behavior of SCN-lesioned chipmunks in natural habitat:a pilot study[J]. J. Biol. Rhythms., 1998, 13(3):229-244
    OUYANG Y, ANDERSSON C R, KONDO T, et al. Resonating circadian clocks enhance fitness in cyanobacteria[J]. Proc. Natl. Acad. Sci. USA., 1998, 95:8660-8664
    DODD A N, SALATHIA N, HALL A, et al. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage[J]. Science, 2005, 309(5734):630-633
    MERGENHAGEN D, MERGENHAGEN E. The biological clock of Chlamydomonas reinhardii in space[J]. Eur. J. Cell. Biol., 1987, 43(2):203-207
    SULZMAN F M, ELLMAN D, FULLER C A, et al. Neurospora circadian rhythms in space:a reexamination of the endogenous-exogenous question[J]. Science, 1984, 225(4658):232-234
    HAHN P M, HOSHIZAKI T, ADEV W R. Circadian rhythms of the Macaca nemestrina monkey in Biosatellite 3[J]. Aerosp. Med., 1971, 42(3):295
    HOBAN-HIGGINS T M, ALPATOV A M, WASSMER G T, et al. Gravity and light effects on the circadian clock of a desert beetle, Trigonoscelis gigas[J]. J. Insect. Physiol., 2003, 49(7):671-675
    FULLER C A, HOBAN-HIGGINS T M, KLIMOVITSKY V Y, et al. Primate circadian rhythms during spaceflight:results from Cosmos 2044 and 2229[J]. J. Appl. Physiol., 1996, 81(1):188-193
    HOLLEY D C, DEROSHIA C W, MORAN M M, et al. Chronic centrifugation (hypergravity) disrupts the circadian system of the rat[J]. J. Appl. Physiol., 2003, 95(3):1266-1278
    FUJITA S, RUTTER L, ONG Q, et al. Integrated rna-seq analysis indicates asynchrony in clock genes between tissues under spaceflight[J]. Life, 2020, 10(9):196
    MA L, MA J, XU K. Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster[J]. PloS One, 2015, 10(3):0121600
    GUEGUINOU N, JEANDEL J, KAMINSKI S, et al. Modulation of iberian ribbed newt complement component C3 by stressors similar to those encountered during a stay onboard the international space station[J]. Int. J. Mol. Sci., 2019, 20(7):1579
    FULLER C A, MURAKAMI D M, DEMARIA-PESCE V H. Entrainment of circadian rhythms in the rat by daily one hour G pulses[J]. Physiologist, 1992, 35(1):63-64
    CHEN L, ZHANG B, YANG L, et al. BMAL1 disrupted intrinsic diurnal oscillation in rat cerebrovascular contractility of simulated microgravity rats by altering circadian regulation of miR-103/CaV1. 2 signal pathway[J]. Int. J. Mol. Sci., 2019, 20(16):3947
    FUKAZAWA T, TANIMOTO K, SHRESTHA L, et al. Simulated microgravity enhances CDDP-induced apoptosis signal via p53-independent mechanisms in cancer cells[J]. PloS One, 2019, 14(7):0219363
    CHOWDHURY B, SEETHARAM A, WANG Z, et al. A study of alterations in DNA epigenetic modifications (5mC and 5hmC) and gene expression influenced by simulated microgravity in human lymphoblastoid cells[J]. PloS One, 2016, 11(1):0147514
    LÜ K, QU L. Influence of simulated microgravity on clock genes expression rhythmicity and underlying blood circulating miRNAs-mRNA co-expression regulatory mechanism in C57BL/6J mice[J]. Cosp, 2014, 40:F4. 4-6-14
    MALLIS M M, DEROSHIA C W. Circadian rhythms, sleep, and performance in space[J]. Aviat. Space. Environ. Med., 2005, 76(6):94-107
    GUNDEL A, DRESCHER J, POLYAKOV V V. Quantity and quality of sleep during the record manned space flight of 438 days[J]. Human Factors Aerosp. Safety, 2001, 1(1):87-98
    MONK T H, BUESSE D J, BILLY B D, et al. Sleep and circadian rhythms in four orbiting astronauts[J]. J. Biol. Rhythms., 1998, 13(3):188-201
    MONK T H. Aging and space flight:findings from the university of pittsburgh[J]. J. Gravit. Physiol., 1999, 6(1):137-140
    LIANG Xiaodi, LIU Zhizhen, CHEN Xianyun, et al. Unbearable lightness of being-the changes in circadian rhythms under microgravity[J]. Chin. Bull. Life. Sci., 2015, 27(11):1433-1439(梁小弟, 刘志臻, 陈现云, 等. 生命中不能承受之轻-微重力条件下生物昼夜节律的变化研究[J]. 生命科学, 2015, 27(11):1433-1439)
    GUNDEL A, POLYAKOV V V, ZULLEY J. The alteration of human sleep and circadian rhythms during spaceflight[J]. J. Sleep. Res., 1997, 6(1):1-8
    MOLDOFSKY H, LUE F, MacFARLANE J, et al. Long-term effects of microgravity on human sleep, cytokine, and endocrines[J]. Gravit. Space. Biol. Bull., 2000, 14:41
    PETIT G, CEBOLLA A M, FATTINGER S, et al. Local sleep-like events during wakefulness and their relationship to decreased alertness in astronauts on ISS[J]. NPJ. Microgravity., 2019, 5(1):1-9
    STOILOVA I M, JORDANOVA M M. Sleep in microgravity[C]//Proceedings of 2nd International Conference on Recent Advances in Space Technologies 2005. Turkey:IEEE, 2005:744-748
    STOILOVA I, ZDRAVEV T, YANEV T. Evaluation of sleep in space flight[J]. C. R. Acad. Bulg. Sci., 2000, 53(6):59
    BARGER L K, FLYNN-EVANS E E, KUBEY A, et al. Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight:an observational study[J]. Lancet. Neurol., 2014, 13(9):904-912
    DIJK D J, NERI D F, WYATT J K, et al. Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights[J]. Am. J. Physiol., 2001, 281:1647-1664
    CHEN H, LÜ K, JI G, et al. Characterization of sleep-wake patterns in crew members under a short-duration spaceflight[J]. Biol. Rhythm. Res., 2020, 51(3):392-407
    LIU Z, WAN Y, ZHANG L, et al. Alterations in the heart rate and activity rhythms of three orbital astronauts on a space mission[J]. Life. Sci. Space. Res., 2015, 4:62-66
    MA Huan, LIU Zhizhen, TIAN Yu, et al. Analysis of alertness and diumal rhythms in astronauts before and after an orbital mission[J]. Space Med. Space Eng., 2017, 6:391-395(马欢, 刘至臻, 田雨, 等. 在轨飞行对航天员警觉度及其昼夜节律的影响[J]. 航天医学与医学工程, 2017, 6:391-395)
    FLYNN-EVANS E E, BARGER L K, KUBEY A A, et al. Circadian misalignment affects sleep and medication use before and during spaceflight[J]. NPJ. Microgravity, 2016, 2(1):1-6
    FROST Jr J D, SHUMATE W H, SALAMY J G, et al. Sleep monitoring:the second manned Skylab mission[J]. Aviat. Space. Environ. Med., 1976, 47(4):372-382
    GUNDERL A, NALISHITIi V, REUCHER E, et al. Sleep and circadian rhythm during a short space mission[J]. Clin. Invest., 1993, 1:718-724
    YAMAMOTO N, OTSUKA K, KUBO Y, et al. Effects of long-term microgravity exposure in space on circadian rhythms of heart rate variability[J]. Chronobiol. Int., 2015, 32(3):327-340
    VERHEYDEN B, BECKERS F, COUCKUYT K, et al. Respiratory modulation of cardiovascular rhythms before and after short-duration human spaceflight[J]. Acta. Physiol., 2007, 191(4):297-308
    MANZEY D, LORENZ B, POLJAKOV V. Mental performance in extreme environments:results from a performance monitoring study during a 438-day spaceflight[J]. Ergonomics, 1998, 41(4):537-559
    SCHIFLETT S G. Fifth Annual Workshop on Space Operations Applications and Research (SOAR'91). NASA CP-3127[M]. Washington:NASA, 1992
    LEACH C S, JOHNSON P C Jr. Fluid and electrolyte control in simulated and actual spaceflight[J]. Physiologist, 1985, 28(6):34-37
    MONK T H, KENNEDY K S, ROSE L R, et al. Decreased human circadian pacemaker influence after 100 days in space:a case study[J]. Psychosom. Med., 2001, 63(6):881-885
    KELLY T H, HIENZ R D, ZACONE T J, et al. Crewmember performance before, during, and after spaceflight[J]. J. Exp. Anal. Behav., 2005, 84(2):227-241
    FLYNN C F. Behavioral health and performance support[M]//Principles of Clinical Medicine for Space Flight. New York:Springer, 2008:391-412
    SOLBIATI S, LANDREANI F, TURCATO M, et al. Analysis of changes in cardiac circadian rhythms of RR and QT induced by a 60-day head-down bed rest with and without nutritional countermeasure[J]. Eur. J. Appl. Physiol., 2020, 120(7):1699-1710
    PUTCHA L. Assessment of sleep dynamics in a simulated space station environment[M]//Isolation-NASA Experiments in Closed-Environment Living (Advanced Human Life Support Enclosed System Final Report). San Diego:American Astronautical Society, 2002:131-139
    WAN Yufeng, ZHANG Lin, YU Xinyang, et al. Influence of a 45 d-6o Head-down bed rest on the concentration and circadian rhythms of urinal calcium and phosphorus[J]. Space Med. Med. Eng., 2015, 28(1):11-15(万宇峰, 张琳,喻昕阳, 等. 45d头低位卧床对尿样Ca、P元素含量及昼夜节律的影响[J]. 航天医学与医学工程, 2015, 28(1):11-15)
    CARSKADON M A, DEMENT W C. Norman human sleep[M]//Principles and Practice of Sleep Medicine. Philadelphia:W.B. Saunders Co, 1989:3-13
    WU B, WANG Y, WU X, et al. On-orbit sleep problems of astronauts and countermeasures[J]. Mil. Med. Res., 2018, 5(1):1-12
    STONER J D. Aircrew fatigue monitoring during sustained flight operations from Souda Bay, Crete, Greece[J]. Aviat. Space. Environ. Med., 1996, 67(9):863-866
    MA H, LI Y, LIANG H, et al. Sleep deprivation and a non-24-h working schedule lead to extensive alterations in physiology and behavior[J]. Faseb. J., 2019, 33(6):6969-6979
    HORNE J A. Dimensions to sleepiness[M]. Sleep, Sleepiness and Performance. Chichester:John Wiley & Sons, 1991:169-196
    BARRATT M R, POOL S L. Principles of Clinical Medicine for Space Flight[M]. New York:Springer, 2008
    FURLAN R, BARBIC F, PIAZZA S, et al. Modifications of cardiac autonomic profile associated with a shift schedule of work[J]. Circulation, 2000, 102(16):1912-1916
    MIZUNO K, INOUE N, KRAFT N, et al. Sleep/wake rhythm changes during a simulation study for long duration space mission (SFINCSS-99)[J]. Aviat. Space. Environ. Med., 2001, 72:237
    KOROS A. An Evaluation of Noise and Its Effects on Shuttle Crew members During STS-50/USML-1[M]. Washington:NASA, 1993
    GOEL N, BASNER M, RAO H, et al. Chapter seven-circadian rhythms, sleep deprivation, and human performance[J]. Prog. Mol. Biol. Transl. Sci., 2013, 119:155-190
    WEST K E, JABLONSKI M R, WARFIELD B, et al. Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans[J]. J. Appl. Physiol., 2011, 110(3):619-626
    PUTCHA L, MARSHBURN T H. Fatigue, sleep, and chronotherapy[M]. Principles of Clinical Medicine for Space Flight. New York:Springer, 2008
    WHITSON P A, PUTCHA L, CHEN Y M, et al. Melatonin and cortisol assessment of circadian shifts in astronauts before flight[J]. J. Pineal. Res., 1995, 18(3):141-147
    SANTY P A, KAPANKA H, DAVIS J R, et al. Analysis of sleep on Shuttle missions[J]. Aviat. Space. Environ. Med., 1988, 59(11):1094-1097
    DES MARAIS D J, WALTER M R. Astrobiology:exploring the origins, evolution, and distribution of life in the universe[J]. Ann. Rev. Ecol. Syst., 1999, 30:397-420
    REFINITTI R. Circadian Physiology[M]. Boca Raton:CRC Press, 2016
    WHITMIRE A M, LEVETON L B, BARGER L, et al. Risk of performance errors due to sleep loss, circadian desynchronization, fatigue, and work overload[R]//Human Health and Performance Risks of Space Exploration Missions:Evidence Reviewed by the NASA Human Research Program. NASA SP-2009-3405. Washington D C:National Aeronautics and Space Administration, 2009
    BARGER L K, WRIGHT K P Jr, BURKE T M, et al. Sleep and cognitive function of crewmembers and mission controllers working 24-h shifts during a simulated 105-day spaceflight mission[J]. Acta. Astronaut., 2014, 93:230-242
    BARGER L K, SULLIVAN J P, VINCENT A S, et al. Learning to live on a Mars day:fatigue countermeasures during the Phoenix Mars Lander mission[J]. Sleep, 2012, 35(10):1423-1435
    BRAINARD G C, HANIFIN J P, GREESON J M, et al. Action spectrum for melatonin regulation in humans:evidence for a novel circadian photoreceptor[J]. J. Neurosci., 2001, 21:6405-6412
    WRIGHT K P Jr, HULL J T, CZEISLER C A. Relationship between alertness, performance, and body temperature in humans[J]. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2002, 283:1370-1377
    BASNER M, DINGES D F, MOLLICONE D, et al. Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing[J]. Proc. Natl. Acad. Sci. USA., 2013, 110(7):2635-2640
    VIGO D E, TUERLINCKX F, OGRINZ B, et al. Circadian rhythm of autonomic cardiovascular control during Mars500 simulated mission to Mars[J]. Aviat. Space. Environ. Med., 2013, 84(10):1023-1028
    HEPPENER M. Moon, Mars and Beyond[M]. Stress Challenges and Immunity in Space. Switzerland:Springer Cham, 2020:709-733
    GEIGER M, WALCH-LIU P, ENGELS C, et al. Enhanced carbon dioxide leads to a modified diurnal rhythm of nitrate reductase activity and higher levels of amino acids in higher plants[J]. Plant. Cell. Environ., 1998, 21:253-268
    BANFIELD D, SPIGA A, NEWMAN C, et al. The atmosphere of Mars as observed by InSight[J]. Nat. Geosci., 2020, 13:190-198
    BROWN F A, HASTINGS J W, PALMER J D. The Biological Cloc:Two Views[M]. New York:Academic Press, 1970
    PITTENDRIGH C S. On the biological problems to be attacked with a series of U.S. satellites in 1966[J]. Life. Sci. Space. Res., 1965, 3:206-214
    BOIVIN D B, TREMBLAY G M, JAMES F O. Working on atypical schedules[J]. Sleep. Med., 2007, 8(6):578-589
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