Abstract
The circadian clock can only reliably fulfil its function if it is stably entrained. Most clocks use the light–dark cycle as environmental signal (zeitgeber) for this active synchronisation. How we think about clock function and entrainment has been strongly influenced by the early concepts of the field’s pioneers, and the astonishing finding that circadian rhythms continue a self-sustained oscillation in constant conditions has become central to our understanding of entrainment.
Here, we argue that we have to rethink these initial circadian dogmas to fully understand the circadian programme and how it entrains. Light is also the prominent zeitgeber for the human clock, as has been shown experimentally in the laboratory and in large-scale epidemiological studies in real life, and we hypothesise that social zeitgebers act through light entrainment via behavioural feedback loops (zeitnehmer). We show that human entrainment can be investigated in detail outside of the laboratory, by using the many ‘experimental’ conditions provided by the real world, such as daylight savings time, the ‘forced synchrony’ imposed by the introduction of time zones, or the fact that humans increasingly create their own light environment. The conditions of human entrainment have changed drastically over the past 100 years and have led to an increasing discrepancy between biological and social time (social jetlag). The increasing evidence that social jetlag has detrimental consequences for health suggests that shift-work is only an extreme form of circadian misalignment, and that the majority of the population in the industrialised world suffers from a similarly ‘forced synchrony’.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abraham U, Granada AANE, Westermark PALO, Heine M, Herzel H, Kramer A (2010) Coupling governs entrainment range of circadian clocks. Mol Syst Biol 6:1–13
Agez L, Laurent V, Guerrero HY, Pevet P, Masson-Pevet M, Gauer F (2009) Endogenous melatonin provides an effective circadian message to both the suprachiasmatic nuclei and the pars tuberalis of the rat. J Pineal Res 46:95–105
Allebrandt KV, Teder-Laving M, Akyol M, Pichler I, Muller-Myhsok B, Pramstaller P, Merrow M, Meitinger T, Metspalu A, Roenneberg T (2011a) CLOCK gene variants associate with sleep duration in two independent populations. Biol Psychiatry 67:1040–1047
Allebrandt KV, Amin N, Muller-Myhsok B, Esko T, Teder-Laving M, Azevedo RV, Hayward C, van Mill J, Vogelzangs N, Green EW, Melville SA, Lichtner P, Wichmann HE, Oostra BA, Janssens AC, Campbell H, Wilson JF, Hicks AA, Pramstaller PP, Dogas Z, Rudan I, Merrow M, Penninx B, Kyriacou CP, Metspalu A, van Duijn CM, Meitinger T, Roenneberg T (2011b) A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila. Mol Psychiatry. doi:10.1038/mp.2011.142
Asher G, Schibler U (2011) Crosstalk between components of circadian and metabolic cycles in mammals. Cell Metab 13:125–137
Bachleitner W, Kempinger L, Wulbeck C, Rieger D, Helfrich-Forster C (2007) Moonlight shifts the endogenous clock of Drosophila melanogaster. Proc Natl Acad Sci USA 104:3538–3543
Baggs JE, Price TS, DiTacchio L, Panda S, FitzGerald GA, Hogenesch JB (2009) Network features of the mammalian circadian clock. PLoS Biol 7:e52
Brown SA, Zumbrunn G, Fleury-Olela F, Preitner N, Schibler U (2002) Rhythms of mammalian body temperature can sustain peripheral circadian clocks. Curr Biol 12:1574–1583
Brown SA, Kunz D, Dumas A, Westermark PO, Vanselow K, Tilmann-Wahnschaffe A, Herzel H, Kramer A (2008) Molecular insights into human daily behavior. Proc Natl Acad Sci USA 105:1602–1607
Buhr ED, Yoo SH, Takahashi JS (2010) Temperature as a universal resetting cue for mammalian circadian oscillators. Science 330:379–385
Bünning E (1960) Circadian rhythms and the time measurement in photoperiodism. Cold Spring Harb Symp Quant Biol 25:249–256
Carskadon MA (2011) Sleep in adolescents: the perfect storm. Pediatr Clin North Am 58:637–647
Chang AM, Reid KJ, Gourineni R, Zee PC (2009) Sleep timing and circadian phase in delayed sleep phase syndrome. J Biol Rhythms 24:313–321
Comas M, Beersma DG, Spoelstra K, Daan S (2006) Phase and period responses of the circadian system of mice (Mus musculus) to light stimuli of different duration. J Biol Rhythms 21:362–372
Comas M, Beersma DG, Spoelstra K, Daan S (2007) Circadian response reduction in light and response restoration in darkness: a “skeleton” light pulse PRC study in mice (Mus musculus). J Biol Rhythms 22:432–444
Comas M, Beersma DG, Hut RA, Daan S (2008) Circadian phase resetting in response to light–dark and dark–light transitions. J Biol Rhythms 23:425–434
Czeisler CA, Shanahan TL, Kerman EB, Martens H, Brotman DJ, Emens JS, Klein T, Rizzo JF (1995) Suppression of melatonin secretion in some blind patients by exposure to bright light. N Engl J Med 332:6–55
Czeisler CA, Allan JS, Strogatz SH, Ronda JM, Sanchez R, Rios CD, Freitag WO, Richardson GS, Kronauer RE (1986) Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle. Science 233:667–671
Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchel JF, Rimmer DW, Ronda JM, Silva EJ, Allan JS, Emens JS, Dijk D-J, Kronauer RE (1999) Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 284:2177–2181
Daan S, Pittendrigh CS (1976) A functional analysis of circadian pacemakers in nocturnal rodents: II. The variability of phase response curves. J Comp Physiol A 106:253–266
Daan S, Spoelstra K, Albrecht U, Schmutz I, Daan M, Daan B, Rienks F, Poletaeva I, Dell’Omo G, Vyssotski A, Lipp HP (2011) Lab mice in the field: unorthodox daily activity and effects of a dysfunctional circadian clock allele. J Biol Rhythms 26:118–129
De Mairan JJdO (1729) Observation botanique. Histoir de l’Academie Royale des Science:35–36
Dibner C, Schibler U, Albrecht U (2010) The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 72:517–549
Duffy JF, Zeitzer JM, Rimmer DW, Klerman EB, Dijk DJ, Czeisler CA (2002) Peak of circadian melatonin rhythm occurs later within the sleep of older subjects. Am J Physiol Endocrinol Metab 282:E297–303
Edmunds LN Jr (1984) Cell cycle clocks. Marcel Dekker, New York
Freedman MS, Lucas RJ, Soni B, von Schantz M, Muñoz M, David-Gray Z, Foster RG (1999) Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284:502–504
Frisch K (1967) The dance language and orientation of bees. The Belknap Press of Harvard University Press, Cambridge, MA
Gwinner E (1996) Circadian and circannual programmes in avian migration. J Exp Biol 199:39–48
Hagenauer MH, Lee TM (2012) The neuroendocrine control of the circadian system: adolescent chronotype. Front Neuroendocrinol 33:211–229
Hastings JW, Sweeney BM (1957) On the mechanism of temperature independence in a biological clock. Proc Natl Acad Sci USA 43:804–811
Hastings JW, Sweeney BM (1958) A persistent diurnal rhythm of luminescence in Gonyaulax polyedra. Biol Bull 115:440–458
Honma K, Hashimoto S, Nakao M, Honma S (2003) Period and phase adjustments of human circadian rhythms in the real world. J Biol Rhythms 18:261–270
Horne JA, Östberg O (1976) A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol 4:97–110
Huang W, Ramsey KM, Marcheva B, Bass J (2011) Circadian rhythms, sleep, and metabolism. J Clin Invest 121:2133–2141
Johnson CH, Golden SS, Ishiura M, Kondo T (1996) Circadian clocks in prokaryotes. Mol Microbiol 21:5–11
Jones CR, Campbell SS, Zone SE, Cooper F, DeSano A, Murphy PJ, Jones B, Czajkowski L, Ptacek LJ (1999) Familial advanced sleep-phase syndrome: a short-period circadian rhythm variant in humans. Nat Med 5:1062–1065
Kantermann T, Juda M, Merrow M, Roenneberg T (2007) The human circadian clock’s seasonal adjustment is disrupted by daylight saving time. Curr Biol 17(22):1996–2000. doi:10.1016/j.cub.2007.10.025
Klerman EB, Dijk D-J (2005) Interindividual variation in sleep duration and its association with sleep debt in young adults. Sleep 28:1253–1259
Klerman EB, Rimmer DW, Dijk D-J, Kronauer RE, Rizzo JFI, Czeisler CA (1998) Nonphotic entrainment of the human circadian pacemaker. Am J Physiol 274:R991–R996
Kramer G (1952) Experiments on bird orientation. Ibis 94:265–285
Kuroda H, Fukushima M, Nakai M, Katayama T, Murakami N (1997) Daily wheel running activity modifies the period of free-running rhythm in rats via intergeniculate leaflet. Physiol Behav 61:633–637
Lockley SW, Skene DJ, Tabandeh H, Bird AC, Defrance R, Arendt J (1997) Relationship between napping and melatonin in the blind. J Biol Rhythms 12:16–25
Lucas RJ, Hattar S, Takao M, Berson DM, Foster RG, Yau K-W (2003) Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science 299:245–247
McWatters HG, Bastow RM, Hall A, Millar AJ (2000) The ELF3zeitnehmer regulates light signalling to the circadian clock. Nature 408:716–720
Merrow M, Brunner M, Roenneberg T (1999) Assignment of circadian function for the Neurospora clock gene frequency. Nature 399:584–586
Mistlberger RE, Skene DJ (2005) Nonphotic entrainment in humans? J Biol Rhythms 20:339–352
Mohawk JA, Takahashi JS (2011) Cell autonomy and synchrony of suprachiasmatic nucleus circadian oscillators. Trends Neurosci 34(7):349–358
Mongrain V, Lavoie S, Selmaoui B, Paquet J, Dumont M (2004) Phase relationships between sleep-wake cycle and underlying circadian rhythms in morningness-eveningness. J Biol Rhythms 19:248–257
O’Neill JS, Reddy AB (2011) Circadian clocks in human red blood cells. Nature 469:498–503
O’Neill JS, van Ooijen G, Dixon LE, Troein C, Corellou F, Bouget FY, Reddy AB, Millar AJ (2011) Circadian rhythms persist without transcription in a eukaryote. Nature 469:554–558
Peschel N, Helfrich-Forster C (2011) Setting the clock–by nature: circadian rhythm in the fruitfly Drosophila melanogaster. FEBS Lett 585:1435–1442
Pittendrigh CS (1960) Circadian rhythms and the circadian organization of living systems. Cold Spring Harb Symp Quant Biol 25:159–184
Pittendrigh CS (1993) Temporal organization: reflections of a Darwinian clock-watcher. Annu Rev Physiol 55:17–54
Pittendrigh CS, Daan S (1976) A functional analysis of circadian pacemakers in nocturnal rodents: I.-V. (the five papers make up one issue with alternating authorship). J Comp Physiol A 106:223–355
Plautz JD, Kaneko M, Hall JC, Kay SA (1997) Independent photoreceptive circadian clocks throughout Drosophila. Science 278:1632–1635
Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, Rollag MD (2000) A novel human opsin in the inner retina. J Neurosci 20:600–605
Rea MA (1998) Photic entrainment of circadian rhythms in rodents. Chronobiol Int 15:395–423
Rémi J, Merrow M, Roenneberg T (2010) A circadian surface of entrainment: varying T, τ and photoperiod in Neurospora crassa. J Biol Rhythms 25:318–328
Roenneberg T, (2012) What is chronotype? Sleep and Biological Rhythms, 10(2), 75–76. doi:10.1111/j.1479-8425.2012.00541.x
Roenneberg T, Morse D (1993) Two circadian oscillators in one cell. Nature 362:362–364
Roenneberg T, Rehman J (1996) Nitrate, a nonphotic signal for the circadian system. J Fed Am Soc Exp Biol 10:1443–1447
Roenneberg T, Merrow M (1998) Molecular circadian oscillators - an alternative hypothesis. J Biol Rhythms 13:167–179
Roenneberg T, Merrow M (2000) Circadian light input: omnes viae Romam ducunt. Curr Biol 10:R742–R745
Roenneberg T, Merrow M (2002) Life before the clock - modeling circadian evolution. J Biol Rhythms 17:495–505
Roenneberg T, Merrow M (2003) The network of time: understanding the molecular circadian system. Curr Biol 13:R198–R207
Roenneberg T, Merrow M (2007) Entrainment of the human circadian clock. Cold Spring Harb Symp Quant Biol 72:293–299
Roenneberg T, Merrow M, Eisensamer B (1998) Cellular mechanisms of circadian systems. Zool Anal Complex Syst 100:273–286
Roenneberg T, Wirz-Justice A, Merrow M (2003) Life between clocks - daily temporal patterns of human chronotypes. J Biol Rhythms 18:80–90
Roenneberg T, Kumar CJ, Merrow M (2007a) The human circadian clock entrains to sun time. Curr Biol 17:R44–R45
Roenneberg T, Rémi J, Merrow M (2010a) Modelling a circadian surface. J Biol Rhythms 25:340–349
Roenneberg T, Chua EJ, Bernardo R, Mendoza E (2008) Modelling biological rhythms. Curr Biol 18:826–835
Roenneberg T, Hut R, Daan S, Merrow M (2010b) Entrainment concepts revisited. J Biol Rhythms 25:329–339
Roenneberg T, Allebrandt KV, Merrow M, Vetter C (2012) Social jetlag and obesity. Curr Biol 22:939–943
Roenneberg T, Kuehnle T, Pramstaller PP, Ricken J, Havel M, Guth A, Merrow M (2004) A marker for the end of adolescence. Curr Biol 14:R1038–R1039
Roenneberg T, Kuehnle T, Juda M, Kantermann T, Allebrandt K, Gordijn M, Merrow M (2007b) Epidemiology of the human circadian clock. Sleep Med Rev 11:429–438
Sack RL, Lewy AJ, Blood ML, Keith LD, Nakagawa H (1992) Circadian rhythm abnormalities in totally blind people: incidence and clinical significance. J Clin Endocrinol Metab 75:127–134
Scheer FAJL, Hilton MF, Mantzoros CS, Shea SA (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 106:4453–4458
Schibler U, Ripperger J, Brown SA (2003) Peripheral circadian oscillators in mammals: time and food. J Biol Rhythms 18:250–260
Steinlechner S, Jacobmeier B, Scherbarth F, Dernbach H, Kruse F, Albrecht U (2002) Robust circadian rhythmicity of Per1 and Per2 mutant mice in constant light and dynamics of Per1 and Per2 gene expression under long and short photoperiods. J Biol Rhythms 17:202–209
Stokkan KA, Yamazaki S, Tei H, Sakaki Y, Menaker M (2001) Entrainment of the circadian clock in the liver by feeding. Science 291:490–493
Strogatz SH (1987) Human sleep and circadian rhythms: a simple model based on two coupled oscillators. J Math Biol 25:327–347
Thain SC, Hall A, Millar AJ (2000) Functional independence of circadian clocks that regulate plant gene expression. Curr Biol 10:951–956
Toh KL, Jones CR, He Y, Eide EJ, Hinz WA, Virshup DM, Ptacek LJ, Fu YH (2001) An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291:1040–1043
van Esseveldt KE, Lehman MN, Boer GJ (2000) The suprachiasmatic nucleus and the circadian time-keeping system revisited. Brain Res Brain Res Rev 33:34–77
Vanin S, Bhutani S, Montelli S, Menegazzi P, Green EW, Pegoraro M, Sandrelli F, Costa R, Kyriacou CP (2012) Unexpected features of Drosophila circadian behavioural rhythms under natural conditions. Nature 484:371–375
Wever R (1979) The circadian system of man. Springer, Berlin
Wever RA (1989) Light effects on human circadian rhythms: a review of recent Andechs experiments. J Biol Rhythms 4:161–185
Wittmann M, Dinich J, Merrow M, Roenneberg T (2006) Social jetlag: misalignment of biological and social time. Chronobiol Int 23:497–509
Wulff K, Gatti S, Wettstein JG, Foster RG (2010) Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci 11:589–599
Wyatt JK, Ritz-de Cecco A, Czeisler CA, Dijk D-J (1999) Circadian temperature and melatonin rhythms, sleep, and neurobiological function in humans living on a 20-h day. Am J Physiol 277:R1152–1163
Xu Y, Padiath QS, Shapiro RE, Jones CR, Wu SC, Saigoh N, Saigoh K, Ptacek LJ, Fu Y-H (2005) Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome. Nature 434:640–644
Yamazaki S, Numano R, Abe M, Hida A, Takahashi R-I, Ueda M, Block GD, Sakaki Y, Menaker M, Tei H (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288:682–685
Zaidi FH, Hull JT, Peirson SN, Wulff K, Aeschbach D, Gooley JJ, Brainard GC, Gregory-Evans K, Rizzo JF 3rd, Czeisler CA, Foster RG, Moseley MJ, Lockley SW (2007) Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina. Curr Biol 17:2122–2128
Zavada A, Gordijn MCM, Beersma DGM, Daan S, Roenneberg T (2005) Comparison of the Munich chronotype questionnaire with the Horne-Östberg’s morningness-eveningness score. Chronobiol Int 22:267–278
Acknowledgments
Our work was supported by the FP6 programme EUCLOCK (TR, KVA), by the Siemens AG (TR, CV, MJ) and by the German Research Foundation (DFG; TK).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Roenneberg, T., Kantermann, T., Juda, M., Vetter, C., Allebrandt, K.V. (2013). Light and the Human Circadian Clock. In: Kramer, A., Merrow, M. (eds) Circadian Clocks. Handbook of Experimental Pharmacology, vol 217. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25950-0_13
Download citation
DOI: https://doi.org/10.1007/978-3-642-25950-0_13
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-25949-4
Online ISBN: 978-3-642-25950-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)