The chronobiology ( ancient Greek χρόνος chronos , time ') studied as a science branch of biology , the temporal organization of physiological processes and repeated patterns of behavior in organisms . The regularities of recurring phenomena proven here are called biological rhythms (not to be confused with esoteric biorhythm theories ). They occur with different period durations and can be understood as regular adaptations of internal states to external circumstances.
A biological rhythm is often based on an endogenously oscillating subsystem of the organism, the so-called internal clock . The impulses generated by this follow one another at certain time intervals, the duration of which can be influenced by exogenous (external) influences, the so-called timers . In this way, an internal rhythm can be adapted to changes in the environment within certain limits, for example to the time-varying day-night cycle . Light and temperature are important timers. If the internal clock is not synchronized by timers - for example under constant laboratory conditions - many natural rhythms continue to vibrate unchanged and undiminished. However, the period (τ) then only roughly corresponds to that under natural conditions.
The 2017 Nobel Prize for Physiology or Medicine was awarded to Jeffrey C. Hall , Michael Rosbash and Michael W. Young for their discoveries of the molecular mechanisms that underlie the circadian rhythm of cells.
A temporal organization is important for all living organisms, which the adaptation to temporally changing environmental conditions enables more favorable chances of survival. It is therefore not surprising that rhythmic processes have been found in all living beings examined so far. Some examples are cell division , heartbeat , breathing , sleep , hibernation, or the rut or menstrual cycle .
Numerous processes in organisms are interdependent - many are only effective if others have previously taken place, some are only effective when they occur together, others disturb each other, some cancel each other out and some are mutually exclusive. There are processes that only need to be coordinated internally. Other processes should also be adapted to the conditions of the outside world.
In addition, processes can be related to regular external fluctuations in order to reliably organize social behavior with organisms of the same type in a timed manner. Or, in order to be more likely to find those of a different kind - or not to be able to be hit by them. So it makes a difference who is active during the day or at night.
For humans, chronobiological research has become more and more important in recent years, as our way of life increasingly contradicts our 'biological clock'. In addition, it is now accepted in medicine that the time at which drugs are taken has a major influence on their effectiveness. In chemotherapy , for example, much lower concentrations of cytostatic agents can be used if the time window for administration is observed.
Classification according to the period
Biological rhythms occur with periods that range in duration from milliseconds to years. They are roughly classified according to whether their period of oscillation is roughly as long as a day (circadian), significantly longer (infradian) or significantly shorter (ultradian). The usual terms refer to the frequency , i.e. the reciprocal of the period of oscillation. If the period is significantly shorter than 24 hours, it can be repeated more than once a day, i.e. the frequency is more than once a day.
- Infradian rhythms
Infradian rhythms (from Latin infra , “under” and this “day”) have a frequency below that of a day, their oscillation lasts significantly longer than 24 hours. This includes circannual rhythms , i.e. seasonal rhythms roughly in the annual cycle (around 365 days) such as those of hibernation and bird migration . Infradian are also circalunar rhythms that follow a moon phase cycle (about 29.5 days) like those of Palolo times , also so-called "semilunar rhythms" (about 15 days), which are associated with the tidal cycle and according to the interval between two nipptides (at half moon ) or two spring tides (at full and new moon) are clocked, such as the night spawning of the grunions on the beach.
- Circadian rhythms
Circadian rhythms (from Latin around 'approximately' and this 'day') have the frequency of days alternating with night and last around 24 hours, for example the sleep / wake rhythm in humans or the leaf movements of many plants. Circadian rhythms have been best researched to date. Not only because daily cycles are easier to recognize than annual cycles, for example; circadian organized rhythms affect various phenomena of their nature that are significant for humans.
- Ultradian rhythms
Ultradian rhythms (from the Latin ultra 'over' and this 'day') have a frequency above that of a day, their oscillation lasts for less than 24 hours. If it lasts considerably less, it can happen more than once a day. Examples of this are the alternation of activity and rest phases in field mice , the repeated succession of sleep phases in adults or the pulsatile release of pituitary hormones.
The circatidal rhythms play a special role here , with a period of around 12.5 hours, which follow the recurring alternation of ebb and flow and are decisive for many residents of the surf zone. For example, beach-dwelling fiddler crabs only look for food at low tide, whereas crabs living in the water only swim around in the water at high tide.
Biological rhythms in different living things
It has been known since the 1940s that single-cell organisms also have an "internal clock". This made it clear early on that no networks were required for a clock to function. Algae like Euglena or Chlamydomonas have a circadian rhythm of phototaxis . Circadian processes could be found in the Paramecium. Marine dinoflagellates , such as Lingulodinium polyedrum (= Gonyaulax polyedra ), also have a circadian organization. They rise to the surface of the water an hour before sunrise, where they form dense swarms and photosynthesize . Under favorable conditions, they cause what is known as the algae bloom . The single-celled organisms sink back into the depths before sunset. During the night they produce biochemical light with the help of the luciferase system , presumably to ward off their predators, copepods . This behavioral program continues rhythmically in the laboratory under constant conditions.
In plants no central control of the internal clock or pacemaker was found so far. It is currently assumed that the control of physiological processes, in particular photosynthesis and the frequent movements associated with it, is controlled by several clocks distributed throughout the plant.
For other daily occurrences, for example the renewal of the photosynthetic apparatus, a direct light effect on gene expression could also be demonstrated. Protein synthesis takes place daily for the light harvesting complex (Lhc) in the thylakoid membranes of the chloroplasts . Light regulates the transcription and translation of the nuclear-coded genes involved. In the tomato, 19 such Lhc genes are currently (2004) known. Intensive research is currently underway into the transfer of such Lhc genes and their promoters .
In animals , clear pacemaker centers could be located in the central nervous system (CNS). Since, as already mentioned above, rhythms are often associated with light, it is not surprising that these clocks are found in the realm of the visual system:
- with insects in the optical praise;
- in molluscs at the base of the retina ;
- in vertebrates in the suprachiasmatic nucleus (NSC) located above the junction of the optic nerves and / or in the pineal gland (pineal organ, epiphysis); the epiphysis produces the hormone melatonin .
In fish , amphibians , reptiles and many birds , the tissue of the epiphysis is sensitive to light, although it is hidden deep in the brain. In addition, it is still independent in reptiles and some birds and, in addition to the circadian melatonin production, also controls other circadian rhythms such as body temperature and food intake. One can assume that it is older than the NSC in terms of development.
In mammals , the pineal organ is controlled by the suprachiasmatic nucleus . There is now much evidence that other pacemakers exist, for example in the retina . How exactly these clocks work is still unknown.
Chronobiology in humans
Two main categories of chronotypes can be distinguished in the population : some go to bed late and get up later - the “night owls” or late sleepers ; while the "larks" or early risers go to bed early and get up earlier. Since these differences are due to genetic predisposition , "re-education" is as good as impossible. This means that a large part of the population is constantly living against its facilities. In the case of adolescents, who tend to be more “owls” during puberty, it could be demonstrated that postponing the start of school by one hour - especially in winter - led to a general improvement in performance and better health.
Influence of modern lifestyle
Chronobiology is becoming more and more important for humans, as the lifestyle of people in Western cultures is increasingly deviating from the framework conditions set by the biological clock. For example, the proportion of shift workers is increasing .
In addition, people are spending more and more time indoors, where the light radiation is rarely higher than 500 lux . The light intensity is 8,000 lux outdoors when the sky is overcast and up to 100,000 lux on a sunny day. A constant light deficit can lead to sleep and eating disorders , lack of energy and even severe depression . In northern countries (e.g. Norway ), where the light output per day can tend to zero in winter, light therapy is now recognized as effective against so-called winter depression . On the other hand, it is known from a study that the suicide rate in Greenland increases very significantly in summer.
Traveling across several time zones (i.e. in an east-west or west-east direction) also disrupts the circadian system and stresses the entire body (see jetlag ). In the meantime, there is the Human Centric Lighting lighting concept , which counteracts the negative effects of modern lifestyle by designing the lighting according to the model of daylight and thus promoting the circadian rhythm. Users include airlines. Other areas of application are production facilities, offices, schools, hospitals and care and senior facilities.
Knowing how the biorhythm affects functions of the body can also be taken into account when taking medication. Some examples:
- Asthma attacks tend to occur from midnight to early morning, when the airways narrow even in healthy people. For asthma sufferers, it therefore makes sense to take their medication in the evening beforehand.
- Hay fever is often particularly bad in the evening between 7pm and 11pm, when the body is releasing most of the histamine. It is therefore recommended to use antihistamines preferably in the evening.
- Painkillers have a stronger effect in the afternoon and last longer than in the morning, because pain sensitivity is generally lower in the afternoon.
- Anti-inflammatory drugs have fewer side effects when taken in the evening.
- Inflammation of the gastric mucous membranes is often counteracted with acid-binding agents, which have their strongest effect after dinner.
- Active ingredients similar to cortisol should be taken in the morning and possibly additionally in the evening in order to match the rhythm of the body's own hormone.
18th and 19th centuries
The French scholar Jean Jacques d'Ortous de Mairan (1678–1771) reported the daily leaf movements of the mimosa . In experiments he was able to show that the leaves continue to vibrate according to the rhythm of the day even in permanent darkness (DD).
Similar reports on rhythmic phenomena come from among others Carl von Linné (1707–1778), Georg Christoph Lichtenberg (1742–1799), Christoph Wilhelm Hufeland (1762–1836) and Charles Darwin (1809–1882).
Johann Gottfried Zinn made the first record of a circadian rhythm in 1759 with the bean . To do this, he attached a lever mechanism to the leaves of the plant, which transmitted the diurnal movements of the leaves to a rotating roller. If the sheet sank, it left an upward line on the roller, the sheet rose again, the line pointed down again. He followed this constellation over several days, with the light only going on and off in 12-hour alternation for the first three days and remaining off from the fourth day. If the leaf movement could only be attributed to the light-dark change (LD), it would have been expected that the leaf movements would stop with continued darkness (DD). They didn't. At least light was excluded as the cause of these movements. However, until the 1980s, attempts were made to find other exogenous causes.
Scientific research into these phenomena began in the 20th century. The pioneers of chronobiology include: Wilhelm Pfeffer , Erwin Bünning , Karl von Frisch , Jürgen Aschoff , Colin Pittendrigh , Gunther Hildebrandt , and from the 1960s Arthur Winfree .
In 1983, Spacelab 1 had the mold Neurospora on board to test the circadian rhythm outside of the earth. No difference to the control group in Cape Canaveral could be found. Circadian rhythms and, with a probability bordering on certainty, infradian and ultradian rhythms are endogenous phenomena; there is now consensus on this.
An important method in studying these phenomena in the 20th century has been to find and select genetic mutations . The Konopka was the first to succeed in 1970 with the fruit fly Drosophila melanogaster . These small insects have a strong circadian rhythm when the flies hatch from the pupae. This rhythm is usually around 24 hours. This means that the flies do not hatch randomly throughout the day, but at a specific time. If you did not hatch at this time, you will no longer do it that day, but the next day. The offspring of these flies hatch like their parents. Konopka was able to find and breed a variant that did not hatch every 24 hours but every 19 hours - as did their offspring (Pershort), a variant that hatched every 29 hours (Perlong), and a variant without a rhythm (Per-). All of these variants had a defect on the same gene locus . At the end of the 1990s, “clock genes” could also be found in various mammals (Bmal1, Clock, Per1, Per2, Per3, Cry1, Cry2).
The Americans Jeffrey C. Hall and Michael Rosbash (Brandeis University, Boston) researched for the first time in the 1980s how plants, animals and humans adapt their biological rhythm so that it coincides with the day-night rhythm of the earth Michael W. Young (Rockefeller University, New York). You received the Nobel Prize in Medicine in 2017.
Since the 1990s, chronobiology has developed in a strongly interdisciplinary manner; it forms an interface between behavioral biology , physiology , genetics and ecology . Today the department uses molecular biological and mathematical methods. Research into chronobiology in humans also involves psychology and medicine (especially endocrinology ).
The research focuses on the following questions:
- What types of biological rhythms are there?
- Is the rhythm endogenous? If so, how is it generated? Where is the clock oscillator located? How is the oscillator linked to physiological processes?
- What are the timers, i.e. exogenous factors that can influence the inner rhythm?
- How can the timers act on the biological clock in such a way that an adjustment to external cycles occurs, as entrainment or masking ?
- What are the functions of biological rhythms?
Chronobiology deals with plants and animals including humans. It finds practical application in animal and plant breeding, in social medicine (for example for questions about shift work ), in pharmacology and psychiatry . The findings of chronobiology in the areas of sleep medicine , sports medicine and aviation and space medicine are of particular interest . Chronobiology is taught at most universities in different subject areas (e.g. psychiatry, biology, anatomy and psychology). Since 2012 there has been an endowed professorship “Light and Health” at the Munich University of Applied Sciences, which deals with the interdisciplinary effect of light on health, emotions and well-being of people and with Human Centric Lighting .
- Jürgen Aschoff , S. Daan, GA Groos (Eds.): Vertebrate Circadian Systems. Structure and Physiology, Springer Verlag, ISBN 3-540-11664-8 (English).
- Frank Columbus, Kathryn Bailey: Frontiers in chronobiology research. Nova Science Publ., New York 2006, ISBN 1-59454-954-0 .
- Albert J. and Franziska Dietziker: Interplay of the rhythms of life. How body, mind and soul interact. Institute for Chronobiology ISBN 978-3-033-02529-5 .
- Jan-Dirk Fauteck, Imre Kusztrich: Living with the internal clock: How chronobiology influences our health, economy and society. Econ 2006, ISBN 3-430-12670-3 .
- Contribution Fraunhofer IAO: Chronobiological work design
- Gunther Hildebrandt , Maximilian Moser and Michael Lehofer: Chronobiology and Chronomedicine. Hippokrates Verlag, 1998, ISBN 3-7773-1302-5 .
- Nobuya Koike, Seung-Hee Yoo, Hung-Chung Huang, Vivek Kumar, Choogon Lee, Tae-Kyung Kim, Joseph S. Takahashi: Transcriptional architecture and chromatin landscape of the core circadian clock in mammals . In: Science . tape 338 , no. 6105 , October 19, 2012, p. 349–354 , doi : 10.1126 / science.1226339 , PMC 3694775 (free full text).
- Björn Lemmer : Chronopharmacology. Daily rhythms and drug effects . Stuttgart 2004, ISBN 3-8047-1304-1 .
- Gopalaiah Magadi, Kumar Vinod: Biological rhythms. Springer Berlin 2002, ISBN 3-540-42853-4 .
- Ludger Rensing , Ulf Meyer-Grahle, Peter Ruoff: Biological clocks - timing mechanisms in nature. In: Biologie in our Zeit , 31 (5), pp. 305-311 (2001), .
- Dirk Rieger: The internal clock of Drosophila melanogaster - synchronization through light and functional analysis of the circadian pacemaker neurons. (= Dissertation, University of Regensburg 2007, full text ).
- Till Roenneberg : The importance of chronobiology for our life. DuMont Buchverlag, 2010, ISBN 3-8321-9520-3 .
- Peter Spork : The clockwork of nature. Chronobiology - living with the times. Rowohlt Taschenbuch Verlag, Reinbek 2004, ISBN 3-499-61665-3 .
- Arthur T. Winfree: Biological Clocks. Time structures of the living. ISBN 3-922508-87-1 .
- Jürgen Zulley , Barbara Knab: Our internal clock. Herder, Freiburg 2003, ISBN 3-451-05365-9 .
- Peter Spork : Wake up! Departure to a good rested society. Carl Hanser Verlag, Munich 2014, ISBN 978-3-446-44051-7 .
- Chairs and research groups
- Institute for Medical Psychology, Center for Chronobiology, Till Roenneberg, Ludwig Maximilians University Munich
- Center for Chronobiology , University Psychiatric Clinics , Basel, Switzerland
- Charité - Universitätsmedizin Berlin, Research Group Molecular Foundations of Chronobiology
- Department of Neurobiology & Genetics, Charlotte Förster - University of Würzburg
- Institute for Pharmacology & Toxicology Mannheim, Björn Lemmer, University of Heidelberg
- Groningen Center of Behavioral and Cognitive Neuroscience (BCN) , Rijksuniversiteit Groningen, The Netherlands
- Human Research Institute for Health Technology and Prevention Research formerly Joanneum Research , Weiz , Austria
- Nobel Prize in Medicine 2017. US researchers decipher our internal clock on October 2nd
- NR Keyword "Chronobiology" University of Innsbruck
- The Nobel Prize in Physiology or Medicine 2017 Jeffrey C. Hall, Michael Rosbash, Michael W. Young , PM Nobelprize.org, October 2, 2017, accessed October 5, 2017
- Katja Vanselow, Jens T. Vanselow, Pål O. Westermark, Silke Reischl, Bert Maier, Thomas Korte, Andreas Herrmann, Hanspeter Herzel, Andreas Schlosser, Achim Kramer: Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS) . In: Genes & Development . tape 20 , no. October 19 , 2006, ISSN 0890-9369 , p. 2660–2672 , doi : 10.1101 / gad.397006 , PMC 1578693 (free full text).
- Spork The clockwork of nature. 2004; Spork: The sleep book. 2007.
- Greenland: Suicide in summer. image of science, accessed September 8, 2019 .
- licht.de: licht.wissen 19 "Effect of Light on People". In: www.licht.de. licht.de, 2014, accessed on September 17, 2018 .
- Steffen Greeting: Biorhythm. In: Health portal. Retrieved September 30, 2019 .
- Michael field: Chronomedicine. The heart tore at dawn. In: Frankfurter Allgemeine Zeitung. October 11, 2011, p. 2 , accessed September 4, 2015 .
- Nobel Prize for Medicine: How does the internal clock tick? licht.de, December 12, 2017, accessed on August 20, 2018 .
- The faculty receives an endowed professorship for light and health. In: Website of the Faculty of Applied Sciences and Mechatronics. Munich University of Applied Sciences, 2012, accessed on March 23, 2018 .
- Video Human Centric Lighting. In: portal page www.licht.de. licht.de, 2016, accessed on March 23, 2018 .