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Circadian rhythm - Wikipedia
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data-mw="interface" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet edit-page menu__item--page-actions-edit"> <span class="minerva-icon minerva-icon--edit"></span> <span>Edit</span> </a> </li> </ul> </nav> <!-- version 1.0.2 (change every time you update a partial) --> <div id="mw-content-subtitle"></div> </div> <div id="bodyContent" class="content"> <div id="mw-content-text" class="mw-body-content"><script>function mfTempOpenSection(id){var block=document.getElementById("mf-section-"+id);block.className+=" open-block";block.previousSibling.className+=" open-block";}</script><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><section class="mf-section-0" id="mf-section-0"> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">"Circadian" redirects here. For the albums, see <a href="/wiki/Circadian_(5th_Projekt_album)" title="Circadian (5th Projekt album)">Circadian (5th Projekt album)</a> and <a href="/wiki/Circadian_(Intervals_album)" title="Circadian (Intervals album)">Circadian (Intervals album)</a>.</div> <p class="mw-empty-elt"> </p> <style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><p>A <b>circadian rhythm</b> (<span class="rt-commentedText nowrap"><span class="IPA nopopups noexcerpt" lang="en-fonipa"><a href="/wiki/Help:IPA/English" title="Help:IPA/English">/<span style="border-bottom:1px dotted"><span title="'s' in 'sigh'">s</span><span title="/ər/: 'er' in 'letter'">ər</span><span title="/ˈ/: primary stress follows">ˈ</span><span title="'k' in 'kind'">k</span><span title="/eɪ/: 'a' in 'face'">eɪ</span><span title="'d' in 'dye'">d</span><span title="/i/: 'y' in 'happy'">i</span><span title="/ə/: 'a' in 'about'">ə</span><span title="'n' in 'nigh'">n</span></span>/</a></span></span>), or <b>circadian cycle</b>, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., <a href="/wiki/Endogeny_(biology)" title="Endogeny (biology)">endogenous</a>) and responds to the environment (is <a href="/wiki/Entrainment_(chronobiology)" title="Entrainment (chronobiology)">entrained</a> by the environment). Circadian rhythms are regulated by a <a href="/wiki/Circadian_clock" title="Circadian clock">circadian clock</a> whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximize the fitness of an individual. Circadian rhythms have been widely observed in <a href="/wiki/Animals" class="mw-redirect" title="Animals">animals</a>, <a href="/wiki/Plants" class="mw-redirect" title="Plants">plants</a>, <a href="/wiki/Fungi" class="mw-redirect" title="Fungi">fungi</a> and <a href="/wiki/Cyanobacteria" title="Cyanobacteria">cyanobacteria</a> and there is evidence that they evolved independently in each of these kingdoms of life.<sup id="cite_ref-Edgar_459–464_1-0" class="reference"><a href="#cite_note-Edgar_459%E2%80%93464-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p><table class="infobox"><tbody><tr><th colspan="2" class="infobox-above" style="background-color: skyblue">Circadian rhythm</th></tr><tr><td colspan="2" class="infobox-image"><span class="mw-default-size" typeof="mw:File/Frameless"><a href="/wiki/File:Biological_clock_human.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/3/30/Biological_clock_human.svg/220px-Biological_clock_human.svg.png" decoding="async" width="220" height="114" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/30/Biological_clock_human.svg/330px-Biological_clock_human.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/30/Biological_clock_human.svg/440px-Biological_clock_human.svg.png 2x" data-file-width="1200" data-file-height="620"></a></span><div class="infobox-caption">Features of the human circadian biological clock</div></td></tr><tr><th scope="row" class="infobox-label">Pronunciation</th><td class="infobox-data"><style data-mw-deduplicate="TemplateStyles:r1126788409">.mw-parser-output .plainlist ol,.mw-parser-output .plainlist ul{line-height:inherit;list-style:none;margin:0;padding:0}.mw-parser-output .plainlist ol li,.mw-parser-output .plainlist ul li{margin-bottom:0}</style><div class="plainlist"><ul><li><span class="rt-commentedText nowrap"><span class="IPA nopopups noexcerpt" lang="en-fonipa"><a href="/wiki/Help:IPA/English" title="Help:IPA/English">/<span style="border-bottom:1px dotted"><span title="'s' in 'sigh'">s</span><span title="/ər/: 'er' in 'letter'">ər</span><span title="/ˈ/: primary stress follows">ˈ</span><span title="'k' in 'kind'">k</span><span title="/eɪ/: 'a' in 'face'">eɪ</span><span title="'d' in 'dye'">d</span><span title="/i/: 'y' in 'happy'">i</span><span title="/ə/: 'a' in 'about'">ə</span><span title="'n' in 'nigh'">n</span></span>/</a></span></span> </li></ul></div></td></tr><tr><th scope="row" class="infobox-label">Frequency</th><td class="infobox-data">Repeats roughly every 24 hours</td></tr></tbody></table> <p>The term <i>circadian</i> comes from the <a href="/wiki/Latin" title="Latin">Latin</a> <i><i lang="la"><a href="https://en.wiktionary.org/wiki/circa#Latin" class="extiw" title="wikt:circa">circa</a></i></i>, meaning "around", and <i><i lang="la"><a href="https://en.wiktionary.org/wiki/dies#Latin" class="extiw" title="wikt:dies">dies</a></i></i>, meaning "day". Processes with 24-hour cycles are more generally called <b>diurnal rhythms</b>; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental.<sup id="cite_ref-Vitaterna_2001_3-0" class="reference"><a href="#cite_note-Vitaterna_2001-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p><p>Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called <a href="/wiki/Zeitgeber" title="Zeitgeber">zeitgebers</a> (from <a href="/wiki/German_language" title="German language">German</a> <i><i lang="de"><a href="https://en.wiktionary.org/wiki/Zeitgeber#German" class="extiw" title="wikt:Zeitgeber">Zeitgeber</a></i></i> (<style data-mw-deduplicate="TemplateStyles:r1177148991">.mw-parser-output .IPA-label-small{font-size:85%}.mw-parser-output .references .IPA-label-small,.mw-parser-output .infobox .IPA-label-small,.mw-parser-output .navbox .IPA-label-small{font-size:100%}</style><span class="IPA-label IPA-label-small">German:</span> <span class="IPA nowrap" lang="de-Latn-fonipa"><a href="/wiki/Help:IPA/Standard_German" title="Help:IPA/Standard German">[ˈtsaɪtˌɡeːbɐ]</a></span>; <abbr style="font-size:85%" title="literal translation">lit.</abbr><span style="white-space: nowrap;"> </span><span class="gloss-quot">'</span><span class="gloss-text">time giver</span><span class="gloss-quot">'</span>)), which include light, temperature and <a href="/wiki/Redox" title="Redox">redox</a> cycles. In clinical settings, an abnormal circadian rhythm in humans is known as a <a href="/wiki/Circadian_rhythm_sleep_disorder" title="Circadian rhythm sleep disorder">circadian rhythm sleep disorder</a>.<sup id="cite_ref-Bass_348–356_4-0" class="reference"><a href="#cite_note-Bass_348%E2%80%93356-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p> <div id="toc" class="toc" role="navigation" aria-labelledby="mw-toc-heading"><input type="checkbox" role="button" id="toctogglecheckbox" class="toctogglecheckbox" style="display:none"><div class="toctitle" lang="en" dir="ltr"><h2 id="mw-toc-heading">Contents</h2><span class="toctogglespan"><label class="toctogglelabel" for="toctogglecheckbox"></label></span></div> <ul> <li class="toclevel-1 tocsection-1"><a href="#History"><span class="tocnumber">1</span> <span class="toctext">History</span></a></li> <li class="toclevel-1 tocsection-2"><a href="#Criteria"><span class="tocnumber">2</span> <span class="toctext">Criteria</span></a></li> <li class="toclevel-1 tocsection-3"><a href="#Origin"><span class="tocnumber">3</span> <span class="toctext">Origin</span></a></li> <li class="toclevel-1 tocsection-4"><a href="#Importance_in_animals"><span class="tocnumber">4</span> <span class="toctext">Importance in animals</span></a> <ul> <li class="toclevel-2 tocsection-5"><a href="#Effect_of_circadian_disruption"><span class="tocnumber">4.1</span> <span class="toctext">Effect of circadian disruption</span></a></li> <li class="toclevel-2 tocsection-6"><a href="#Effect_of_light%E2%80%93dark_cycle"><span class="tocnumber">4.2</span> <span class="toctext">Effect of light–dark cycle</span></a></li> <li class="toclevel-2 tocsection-7"><a href="#Arctic_animals"><span class="tocnumber">4.3</span> <span class="toctext">Arctic animals</span></a></li> <li class="toclevel-2 tocsection-8"><a href="#Butterflies_and_moths"><span class="tocnumber">4.4</span> <span class="toctext">Butterflies and moths</span></a></li> </ul> </li> <li class="toclevel-1 tocsection-9"><a href="#In_plants"><span class="tocnumber">5</span> <span class="toctext">In plants</span></a></li> <li class="toclevel-1 tocsection-10"><a href="#In_Drosophila"><span class="tocnumber">6</span> <span class="toctext">In <i>Drosophila</i></span></a> <ul> <li class="toclevel-2 tocsection-11"><a href="#PER-TIM_model"><span class="tocnumber">6.1</span> <span class="toctext">PER-TIM model</span></a></li> </ul> </li> <li class="toclevel-1 tocsection-12"><a href="#In_mammals"><span class="tocnumber">7</span> <span class="toctext">In mammals</span></a> <ul> <li class="toclevel-2 tocsection-13"><a href="#Humans"><span class="tocnumber">7.1</span> <span class="toctext">Humans</span></a></li> <li class="toclevel-2 tocsection-14"><a href="#Biological_markers_and_effects"><span class="tocnumber">7.2</span> <span class="toctext">Biological markers and effects</span></a></li> <li class="toclevel-2 tocsection-15"><a href="#Outside_the_%22master_clock%22"><span class="tocnumber">7.3</span> <span class="toctext">Outside the "master clock"</span></a></li> </ul> </li> <li class="toclevel-1 tocsection-16"><a href="#Light_and_the_biological_clock"><span class="tocnumber">8</span> <span class="toctext">Light and the biological clock</span></a></li> <li class="toclevel-1 tocsection-17"><a href="#Enforced_longer_or_shorter_cycles"><span class="tocnumber">9</span> <span class="toctext">Enforced longer or shorter cycles</span></a></li> <li class="toclevel-1 tocsection-18"><a href="#Human_health"><span class="tocnumber">10</span> <span class="toctext">Human health</span></a> <ul> <li class="toclevel-2 tocsection-19"><a href="#Foundation_of_circadian_medicine"><span class="tocnumber">10.1</span> <span class="toctext">Foundation of circadian medicine</span></a></li> <li class="toclevel-2 tocsection-20"><a href="#Causes_of_disruption_to_circadian_rhythms"><span class="tocnumber">10.2</span> <span class="toctext">Causes of disruption to circadian rhythms</span></a> <ul> <li class="toclevel-3 tocsection-21"><a href="#Indoor_lighting"><span class="tocnumber">10.2.1</span> <span class="toctext">Indoor lighting</span></a></li> <li class="toclevel-3 tocsection-22"><a href="#Airline_pilots_and_cabin_crew"><span class="tocnumber">10.2.2</span> <span class="toctext">Airline pilots and cabin crew</span></a></li> <li class="toclevel-3 tocsection-23"><a href="#Effect_of_drugs"><span class="tocnumber">10.2.3</span> <span class="toctext">Effect of drugs</span></a></li> </ul> </li> <li class="toclevel-2 tocsection-24"><a href="#Consequences_of_disruption_to_circadian_rhythms"><span class="tocnumber">10.3</span> <span class="toctext">Consequences of disruption to circadian rhythms</span></a> <ul> <li class="toclevel-3 tocsection-25"><a href="#Disruption"><span class="tocnumber">10.3.1</span> <span class="toctext">Disruption</span></a></li> <li class="toclevel-3 tocsection-26"><a href="#Relationship_with_cardiovascular_disease"><span class="tocnumber">10.3.2</span> <span class="toctext">Relationship with cardiovascular disease</span></a></li> <li class="toclevel-3 tocsection-27"><a href="#Obesity_and_diabetes"><span class="tocnumber">10.3.3</span> <span class="toctext">Obesity and diabetes</span></a></li> <li class="toclevel-3 tocsection-28"><a href="#Cognitive_effects"><span class="tocnumber">10.3.4</span> <span class="toctext">Cognitive effects</span></a></li> </ul> </li> </ul> </li> <li class="toclevel-1 tocsection-29"><a href="#Society_and_culture"><span class="tocnumber">11</span> <span class="toctext">Society and culture</span></a></li> <li class="toclevel-1 tocsection-30"><a href="#See_also"><span class="tocnumber">12</span> <span class="toctext">See also</span></a></li> <li class="toclevel-1 tocsection-31"><a href="#References"><span class="tocnumber">13</span> <span class="toctext">References</span></a></li> <li class="toclevel-1 tocsection-32"><a href="#Further_reading"><span class="tocnumber">14</span> <span class="toctext">Further reading</span></a></li> <li class="toclevel-1 tocsection-33"><a href="#External_links"><span class="tocnumber">15</span> <span class="toctext">External links</span></a></li> </ul> </div> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(1)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="History">History</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=1" title="Edit section: History" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-1 collapsible-block" id="mf-section-1"> <p>The earliest recorded account of a circadian process is credited to <a href="/wiki/Theophrastus" title="Theophrastus">Theophrastus</a>, dating from the 4th century BC, probably provided to him by report of <a href="/wiki/Androsthenes_of_Thasos" title="Androsthenes of Thasos">Androsthenes</a>, a <a href="/wiki/Sea_captain" title="Sea captain">ship's captain</a> serving under <a href="/wiki/Alexander_the_Great" title="Alexander the Great">Alexander the Great</a>. In his book, 'Περὶ φυτῶν ἱστορία', or 'Enquiry into plants', Theophrastus describes a "tree with many leaves like the <a href="/wiki/Rose" title="Rose">rose</a>, and that this closes at night, but opens at sunrise, and by noon is completely unfolded; and at evening again it closes by degrees and remains shut at night, and the natives say that it goes to sleep."<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> The tree mentioned by him was much later identified as the <a href="/wiki/Tamarind" title="Tamarind">tamarind</a> tree by the botanist, H Bretzl, in his book on the botanical findings of the Alexandrian campaigns.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>The observation of a circadian or diurnal process in humans is mentioned in <a href="/wiki/History_of_Chinese_medicine" class="mw-redirect" title="History of Chinese medicine">Chinese medical texts</a> dated to around the 13th century, including the <i>Noon and Midnight Manual</i> and the <i>Mnemonic Rhyme to Aid in the Selection of Acu-points According to the Diurnal Cycle, the Day of the Month and the Season of the Year</i>.<sup id="cite_ref-cl_7-0" class="reference"><a href="#cite_note-cl-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> </p><p>In 1729, French scientist <a href="/wiki/Jean-Jacques_d%27Ortous_de_Mairan" title="Jean-Jacques d'Ortous de Mairan">Jean-Jacques d'Ortous de Mairan</a> conducted the first experiment designed to distinguish an endogenous clock from responses to daily stimuli. He noted that 24-hour patterns in the movement of the leaves of the plant <i><a href="/wiki/Mimosa_pudica" title="Mimosa pudica">Mimosa pudica</a></i> persisted, even when the plants were kept in constant darkness.<sup id="cite_ref-de_mairan_1729_8-0" class="reference"><a href="#cite_note-de_mairan_1729-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid16761955_9-0" class="reference"><a href="#cite_note-pmid16761955-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p><p>In 1896, Patrick and Gilbert observed that during a prolonged period of <a href="/wiki/Sleep_deprivation" title="Sleep deprivation">sleep deprivation</a>, sleepiness increases and decreases with a period of approximately 24 hours.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> In 1918, <a href="/w/index.php?title=J.S._Szymanski&action=edit&redlink=1" class="new" title="J.S. Szymanski (page does not exist)">J.S. Szymanski</a> showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p><p>In the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. <a href="/wiki/Auguste_Forel" title="Auguste Forel">Auguste Forel</a>, <a href="/wiki/Ingeborg_Beling" title="Ingeborg Beling">Ingeborg Beling</a>, and Oskar Wahl conducted numerous experiments to determine whether this rhythm was attributable to an endogenous clock.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> The existence of circadian rhythm was independently discovered in <a href="/wiki/Drosophila_melanogaster" title="Drosophila melanogaster">fruit flies</a> in 1935 by two German zoologists, <a href="/w/index.php?title=Hans_Kalmus&action=edit&redlink=1" class="new" title="Hans Kalmus (page does not exist)">Hans Kalmus</a> and <a href="/wiki/Erwin_B%C3%BCnning" title="Erwin Bünning">Erwin Bünning</a>.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pitt93_14-0" class="reference"><a href="#cite_note-pitt93-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>In 1954, an important experiment reported by <a href="/wiki/Colin_Pittendrigh" title="Colin Pittendrigh">Colin Pittendrigh</a> demonstrated that <a href="/wiki/Eclosion" class="mw-redirect" title="Eclosion">eclosion</a> (the process of <a href="/wiki/Pupa" title="Pupa">pupa</a> turning into adult) in <i><a href="/wiki/Drosophila_pseudoobscura" title="Drosophila pseudoobscura">Drosophila pseudoobscura</a></i> was a circadian behaviour. He demonstrated that while temperature played a vital role in eclosion rhythm, the period of eclosion was delayed but not stopped when temperature was decreased.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pitt93_14-1" class="reference"><a href="#cite_note-pitt93-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>The term <i>circadian</i> was coined by <a href="/wiki/Franz_Halberg" title="Franz Halberg">Franz Halberg</a> in 1959.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> According to Halberg's original definition: </p> <style data-mw-deduplicate="TemplateStyles:r1244412712">.mw-parser-output .templatequote{overflow:hidden;margin:1em 0;padding:0 32px}.mw-parser-output .templatequotecite{line-height:1.5em;text-align:left;margin-top:0}@media(min-width:500px){.mw-parser-output .templatequotecite{padding-left:1.6em}}</style><blockquote class="templatequote"><p>The term "circadian" was derived from <i>circa</i> (about) and <i>dies</i> (day); it may serve to imply that certain physiologic periods are close to 24 hours, if not exactly that length. Herein, "circadian" might be applied to all "24-hour" rhythms, whether or not their periods, individually or on the average, are different from 24 hours, longer or shorter, by a few minutes or hours.<sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-kouk_18-0" class="reference"><a href="#cite_note-kouk-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup></p></blockquote> <p>In 1977, the International Committee on Nomenclature of the <a href="/w/index.php?title=International_Society_for_Chronobiology&action=edit&redlink=1" class="new" title="International Society for Chronobiology (page does not exist)">International Society for Chronobiology</a> formally adopted the definition: </p> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1244412712"><blockquote class="templatequote"><p>Circadian: relating to biologic variations or rhythms with a frequency of 1 cycle in 24 ± 4 h; <i>circa</i> (about, approximately) and <i>dies</i> (day or 24 h). Note: term describes rhythms with an about 24-h cycle length, whether they are frequency-synchronized with (acceptable) or are desynchronized or free-running from the local environmental time scale, with periods of slightly yet consistently different from 24-h.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup></p></blockquote> <p><a href="/wiki/Ron_Konopka" class="mw-redirect" title="Ron Konopka">Ron Konopka</a> and <a href="/wiki/Seymour_Benzer" title="Seymour Benzer">Seymour Benzer</a> identified the first clock mutation in <i>Drosophila</i> in 1971, naming the gene "<a href="/wiki/Period_(gene)" title="Period (gene)">period</a>" (<i>per</i>) gene, the first discovered genetic determinant of behavioral rhythmicity.<sup id="cite_ref-pmid5002428_20-0" class="reference"><a href="#cite_note-pmid5002428-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> The <i>per</i> gene was isolated in 1984 by two teams of researchers. Konopka, Jeffrey Hall, Michael Roshbash and their team showed that <i>per</i> locus is the centre of the circadian rhythm, and that loss of <i>per</i> stops circadian activity.<sup id="cite_ref-reddy_21-0" class="reference"><a href="#cite_note-reddy-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-zehring_22-0" class="reference"><a href="#cite_note-zehring-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> At the same time, Michael W. Young's team reported similar effects of <i>per</i>, and that the gene covers 7.1-kilobase (kb) interval on the X chromosome and encodes a 4.5-kb poly(A)+ RNA.<sup id="cite_ref-bargi1_23-0" class="reference"><a href="#cite_note-bargi1-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-bargi2_24-0" class="reference"><a href="#cite_note-bargi2-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> They went on to discover the key genes and neurones in <i>Drosophila</i> circadian system, for which Hall, Rosbash and Young received the <a href="/wiki/Nobel_Prize_in_Physiology_or_Medicine" title="Nobel Prize in Physiology or Medicine">Nobel Prize in Physiology or Medicine 2017</a>.<sup id="cite_ref-nobel17_25-0" class="reference"><a href="#cite_note-nobel17-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Joseph_Takahashi" title="Joseph Takahashi">Joseph Takahashi</a> discovered the first mammalian circadian clock mutation (<i>clockΔ19</i>) using mice in 1994.<sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> However, recent studies show that deletion of <i>clock</i> does not lead to a behavioral phenotype (the animals still have normal circadian rhythms), which questions its importance in rhythm generation.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> </p><p>The first human clock mutation was identified in an extended Utah family by Chris Jones, and genetically characterized by Ying-Hui Fu and Louis Ptacek. Affected individuals are extreme '<a href="/wiki/Lark_(person)" title="Lark (person)">morning larks</a>' with 4-hour advanced sleep and other rhythms. This form of <a href="/wiki/Familial_advanced_sleep_phase_syndrome" class="mw-redirect" title="Familial advanced sleep phase syndrome">familial advanced sleep phase syndrome</a> is caused by a single <a href="/wiki/Amino_acid" title="Amino acid">amino acid</a> change, S662➔G, in the human PER2 protein.<sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(2)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="Criteria">Criteria</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=2" title="Edit section: Criteria" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-2 collapsible-block" id="mf-section-2"> <p>To be called circadian, a biological rhythm must meet these three general criteria:<sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> </p> <ol><li><b>The rhythm has an endogenously derived free-running period of time that lasts approximately 24 hours.</b> The rhythm persists in constant conditions, i.e. constant darkness, with a period of about 24 hours. The period of the rhythm in constant conditions is called the free-running period and is denoted by the Greek letter τ (tau). The rationale for this criterion is to distinguish circadian rhythms from simple responses to daily external cues. A rhythm cannot be said to be <a href="/wiki/Endogenous" class="mw-redirect" title="Endogenous">endogenous</a> unless it has been tested and persists in conditions without external periodic input. In diurnal animals (active during daylight hours), in general τ is slightly greater than 24 hours, whereas, in nocturnal animals (active at night), in general τ is shorter than 24 hours.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (November 2024)">citation needed</span></a></i>]</sup></li> <li><b>The rhythms are entrainable.</b> The rhythm can be reset by exposure to external stimuli (such as light and heat), a process called <a href="/wiki/Entrainment_(chronobiology)" title="Entrainment (chronobiology)">entrainment</a>. The external stimulus used to entrain a rhythm is called the <a href="/wiki/Zeitgeber" title="Zeitgeber">zeitgeber</a>, or "time giver". Travel across <a href="/wiki/Time_zone" title="Time zone">time zones</a> illustrates the ability of the human biological clock to adjust to the local time; a person will usually experience <a href="/wiki/Jet_lag" title="Jet lag">jet lag</a> before entrainment of their circadian clock has brought it into sync with local time.</li> <li><b>The rhythms exhibit temperature compensation.</b> In other words, they maintain circadian periodicity over a range of physiological temperatures. Many organisms live at a broad range of temperatures, and differences in thermal energy will affect the <a href="/wiki/Chemical_kinetics" title="Chemical kinetics">kinetics</a> of all molecular processes in their cell(s). In order to keep track of time, the organism's circadian clock must maintain roughly a 24-hour periodicity despite the changing kinetics, a property known as temperature compensation. The <a href="/wiki/Q10_(temperature_coefficient)" title="Q10 (temperature coefficient)">Q<sub>10</sub> temperature coefficient</a> is a measure of this compensating effect. If the Q<sub>10</sub> coefficient remains approximately 1 as temperature increases, the rhythm is considered to be temperature-compensated.</li></ol> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(3)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="Origin">Origin</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=3" title="Edit section: Origin" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-3 collapsible-block" id="mf-section-3"> <style data-mw-deduplicate="TemplateStyles:r1251242444">.mw-parser-output .ambox{border:1px solid #a2a9b1;border-left:10px solid #36c;background-color:#fbfbfb;box-sizing:border-box}.mw-parser-output .ambox+link+.ambox,.mw-parser-output .ambox+link+style+.ambox,.mw-parser-output .ambox+link+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+style+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+link+.ambox{margin-top:-1px}html body.mediawiki .mw-parser-output .ambox.mbox-small-left{margin:4px 1em 4px 0;overflow:hidden;width:238px;border-collapse:collapse;font-size:88%;line-height:1.25em}.mw-parser-output .ambox-speedy{border-left:10px solid #b32424;background-color:#fee7e6}.mw-parser-output .ambox-delete{border-left:10px solid #b32424}.mw-parser-output .ambox-content{border-left:10px solid #f28500}.mw-parser-output .ambox-style{border-left:10px solid #fc3}.mw-parser-output .ambox-move{border-left:10px solid #9932cc}.mw-parser-output .ambox-protection{border-left:10px solid #a2a9b1}.mw-parser-output .ambox .mbox-text{border:none;padding:0.25em 0.5em;width:100%}.mw-parser-output .ambox .mbox-image{border:none;padding:2px 0 2px 0.5em;text-align:center}.mw-parser-output .ambox .mbox-imageright{border:none;padding:2px 0.5em 2px 0;text-align:center}.mw-parser-output .ambox .mbox-empty-cell{border:none;padding:0;width:1px}.mw-parser-output .ambox .mbox-image-div{width:52px}@media(min-width:720px){.mw-parser-output .ambox{margin:0 10%}}@media print{body.ns-0 .mw-parser-output .ambox{display:none!important}}</style><table class="box-Missing_information plainlinks metadata ambox ambox-content" role="presentation"><tbody><tr><td class="mbox-text"><div class="mbox-text-span">This section <b>is missing information</b> about independently evolved four times [PMID 11533719].<span class="hide-when-compact"> Please expand the section to include this information. Further details may exist on the <a href="/wiki/Talk:Circadian_rhythm" title="Talk:Circadian rhythm">talk page</a>.</span> <span class="date-container"><i>(<span class="date">September 2021</span>)</i></span></div></td></tr></tbody></table> <p>Circadian rhythms allow organisms to anticipate and prepare for precise and regular environmental changes. They thus enable organisms to make better use of environmental resources (e.g. light and food) compared to those that cannot predict such availability. It has therefore been suggested that circadian rhythms put organisms at a selective advantage in evolutionary terms. However, rhythmicity appears to be as important in regulating and coordinating <i>internal</i> metabolic processes, as in coordinating with the <i>environment</i>.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> This is suggested by the maintenance (heritability) of circadian rhythms in fruit flies after several hundred generations in constant laboratory conditions,<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> as well as in creatures in constant darkness in the wild, and by the experimental elimination of behavioral—but not physiological—circadian rhythms in <a href="/wiki/Quail" title="Quail">quail</a>.<sup id="cite_ref-35" class="reference"><a href="#cite_note-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p><p>What drove circadian rhythms to evolve has been an enigmatic question. Previous hypotheses emphasized that photosensitive proteins and circadian rhythms may have originated together in the earliest cells, with the purpose of protecting replicating DNA from high levels of damaging <a href="/wiki/Ultraviolet" title="Ultraviolet">ultraviolet</a> radiation during the daytime. As a result, replication was relegated to the dark. However, evidence for this is lacking: in fact the simplest organisms with a circadian rhythm, the cyanobacteria, do the opposite of this: they divide more in the daytime.<sup id="cite_ref-37" class="reference"><a href="#cite_note-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> Recent studies instead highlight the importance of co-evolution of <a href="/wiki/Redox" title="Redox">redox</a> proteins with circadian oscillators in all three domains of life following the <a href="/wiki/Great_Oxidation_Event" title="Great Oxidation Event">Great Oxidation Event</a> approximately 2.3 billion years ago.<sup id="cite_ref-Edgar_459–464_1-1" class="reference"><a href="#cite_note-Edgar_459%E2%80%93464-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Bass_348–356_4-1" class="reference"><a href="#cite_note-Bass_348%E2%80%93356-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> The current view is that circadian changes in environmental oxygen levels and the production of <a href="/wiki/Reactive_oxygen_species" title="Reactive oxygen species">reactive oxygen species</a> (ROS) in the presence of daylight are likely to have driven a need to evolve circadian rhythms to preempt, and therefore counteract, damaging <a href="/wiki/Redox" title="Redox">redox reactions</a> on a daily basis. </p><p>The simplest known <a href="/wiki/Circadian_clock" title="Circadian clock">circadian clocks</a> are <a href="/wiki/Bacterial_circadian_rhythms" class="mw-redirect" title="Bacterial circadian rhythms">bacterial circadian rhythms</a>, exemplified by the prokaryote <a href="/wiki/Cyanobacteria" title="Cyanobacteria">cyanobacteria</a>. Recent research has demonstrated that the circadian clock of <i><a href="/wiki/Synechococcus_elongatus" title="Synechococcus elongatus">Synechococcus elongatus</a></i> can be reconstituted <i>in vitro</i> with just the three proteins (<a href="/wiki/KaiA" title="KaiA">KaiA</a>, <a href="/wiki/KaiB" title="KaiB">KaiB</a>, <a href="/wiki/KaiC" title="KaiC">KaiC</a>)<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> of their central oscillator. This clock has been shown to sustain a 22-hour rhythm over several days upon the addition of <a href="/wiki/Adenosine_triphosphate" title="Adenosine triphosphate">ATP</a>. Previous explanations of the <a href="/wiki/Prokaryotic" class="mw-redirect" title="Prokaryotic">prokaryotic</a> circadian timekeeper were dependent upon a DNA transcription/translation feedback mechanism.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (November 2013)">citation needed</span></a></i>]</sup> </p><p>A defect in the human homologue of the <i><a href="/wiki/Drosophila" title="Drosophila">Drosophila</a></i> "<a href="/wiki/Period_(gene)" title="Period (gene)">period</a>" gene was identified as a cause of the sleep disorder FASPS (<a href="/wiki/Familial_advanced_sleep_phase_syndrome" class="mw-redirect" title="Familial advanced sleep phase syndrome">Familial advanced sleep phase syndrome</a>), underscoring the conserved nature of the molecular circadian clock through evolution. Many more genetic components of the biological clock are now known. Their interactions result in an interlocked feedback loop of gene products resulting in periodic fluctuations that the cells of the body interpret as a specific time of the day.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> </p><p>It is now known that the molecular circadian clock can function within a single cell. That is, it is cell-autonomous.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> This was shown by <a href="/wiki/Gene_Block" title="Gene Block">Gene Block</a> in isolated mollusk basal retinal neurons (BRNs).<sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> At the same time, different cells may communicate with each other resulting in a synchronized output of electrical signaling. These may interface with <a href="/wiki/Endocrine_gland" title="Endocrine gland">endocrine glands</a> of the brain to result in periodic release of hormones. The receptors for these hormones may be located far across the body and synchronize the peripheral clocks of various organs. Thus, the information of the time of the day as relayed by the <a href="/wiki/Human_eye" title="Human eye">eyes</a> travels to the clock in the brain, and, through that, clocks in the rest of the body may be synchronized. This is how the timing of, for example, sleep/wake, body temperature, thirst, and appetite are coordinately controlled by the biological clock.<sup id="cite_ref-42" class="reference"><a href="#cite_note-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(4)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="Importance_in_animals">Importance in animals</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=4" title="Edit section: Importance in animals" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-4 collapsible-block" id="mf-section-4"> <p>Circadian rhythmicity is present in the sleeping and feeding patterns of animals, including human beings. There are also clear patterns of core body temperature, <a href="/wiki/Neural_oscillation" title="Neural oscillation">brain wave</a> activity, <a href="/wiki/Hormone" title="Hormone">hormone</a> production, cell regeneration, and other biological activities. In addition, <a href="/wiki/Photoperiodism" title="Photoperiodism">photoperiodism</a>, the physiological reaction of organisms to the length of day or night, is vital to both plants and animals, and the circadian system plays a role in the measurement and interpretation of day length. Timely prediction of seasonal periods of weather conditions, food availability, or predator activity is crucial for survival of many species. Although not the only parameter, the changing length of the photoperiod (day length) is the most predictive environmental cue for the seasonal timing of physiology and behavior, most notably for timing of migration, hibernation, and reproduction.<sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Effect_of_circadian_disruption">Effect of circadian disruption</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=5" title="Edit section: Effect of circadian disruption" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p><a href="/wiki/Mutation" title="Mutation">Mutations</a> or <a href="/wiki/Deletion_(genetics)" title="Deletion (genetics)">deletions</a> of <a href="/wiki/CLOCK" title="CLOCK">clock</a> genes in mice have demonstrated the importance of body clocks to ensure the proper timing of cellular/metabolic events; clock-mutant mice are <a href="/wiki/Polyphagia" title="Polyphagia">hyperphagic</a> and obese, and have altered glucose metabolism.<sup id="cite_ref-pmid15845877_45-0" class="reference"><a href="#cite_note-pmid15845877-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> In mice, deletion of the <a href="/wiki/Rev-ErbA_alpha" title="Rev-ErbA alpha">Rev-ErbA alpha</a> clock gene can result in diet-induced <a href="/wiki/Obesity" title="Obesity">obesity</a> and changes the balance between <a href="/wiki/Glucose" title="Glucose">glucose</a> and lipid utilization, predisposing to <a href="/wiki/Diabetes" title="Diabetes">diabetes</a>.<sup id="cite_ref-pmid22562834_46-0" class="reference"><a href="#cite_note-pmid22562834-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> However, it is not clear whether there is a strong association between clock gene polymorphisms in humans and the susceptibility to develop the metabolic syndrome.<sup id="cite_ref-pmid22828941_47-0" class="reference"><a href="#cite_note-pmid22828941-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid18071340_48-0" class="reference"><a href="#cite_note-pmid18071340-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Effect_of_light–dark_cycle"><span id="Effect_of_light.E2.80.93dark_cycle"></span>Effect of light–dark cycle</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=6" title="Edit section: Effect of light–dark cycle" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>The rhythm is linked to the light–dark cycle. Animals, including humans, kept in total darkness for extended periods eventually function with a <a href="/wiki/Free-running_sleep" title="Free-running sleep">free-running</a> rhythm. Their sleep cycle is pushed back or forward each "day", depending on whether their "day", their <a href="/wiki/Endogenous" class="mw-redirect" title="Endogenous">endogenous</a> period, is shorter or longer than 24 hours. The environmental cues that reset the rhythms each day are called zeitgebers.<sup id="cite_ref-health.am_49-0" class="reference"><a href="#cite_note-health.am-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> Totally blind subterranean mammals (e.g., <a href="/wiki/Blind_mole_rat" class="mw-redirect" title="Blind mole rat">blind mole rat</a> <i>Spalax</i> sp.) are able to maintain their endogenous clocks in the apparent absence of external stimuli. Although they lack image-forming eyes, their <a href="/wiki/Photoreceptor_cell" title="Photoreceptor cell">photoreceptors</a> (which detect light) are still functional; they do surface periodically as well.<sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (November 2013)">page needed</span></a></i>]</sup><sup id="cite_ref-50" class="reference"><a href="#cite_note-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> </p><p>Free-running organisms that normally have one or two consolidated sleep episodes will still have them when in an environment shielded from external cues, but the rhythm is not entrained to the 24-hour light–dark cycle in nature. The sleep–wake rhythm may, in these circumstances, become out of phase with other circadian or <a href="/wiki/Ultradian" class="mw-redirect" title="Ultradian">ultradian</a> rhythms such as metabolic, hormonal, CNS electrical, or <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a> rhythms.<sup id="cite_ref-51" class="reference"><a href="#cite_note-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup> </p><p>Recent research has influenced the design of <a href="/wiki/Human_spaceflight" title="Human spaceflight">spacecraft</a> environments, as systems that mimic the light–dark cycle have been found to be highly beneficial to astronauts.<sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)"><span title="Material near this tag may rely on an unreliable or less reliable medical source. (November 2013)">unreliable medical source?</span></a></i>]</sup><sup id="cite_ref-52" class="reference"><a href="#cite_note-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Light_therapy" title="Light therapy">Light therapy</a> has been trialed as a <a href="/wiki/Circadian_rhythm_sleep_disorder#Treatment" title="Circadian rhythm sleep disorder">treatment for sleep disorders</a>. </p> <div class="mw-heading mw-heading3"><h3 id="Arctic_animals">Arctic animals</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=7" title="Edit section: Arctic animals" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>Norwegian researchers at the <a href="/wiki/University_of_Troms%C3%B8" class="mw-redirect" title="University of Tromsø">University of Tromsø</a> have shown that some <a href="/wiki/Arctic#Flora_and_fauna" title="Arctic">Arctic animals</a> (e.g., <a href="/wiki/Rock_Ptarmigan" class="mw-redirect" title="Rock Ptarmigan">ptarmigan</a>, <a href="/wiki/Reindeer" title="Reindeer">reindeer</a>) show circadian rhythms only in the parts of the year that have daily sunrises and sunsets. In one study of reindeer, animals at <a href="/wiki/70th_parallel_north" title="70th parallel north">70 degrees North</a> showed circadian rhythms in the autumn, winter and spring, but not in the summer. Reindeer on <a href="/wiki/Svalbard" title="Svalbard">Svalbard</a> at <a href="/wiki/78th_parallel_north" title="78th parallel north">78 degrees North</a> showed such rhythms only in autumn and spring. The researchers suspect that other Arctic animals as well may not show circadian rhythms in the constant light of summer and the constant dark of winter.<sup id="cite_ref-53" class="reference"><a href="#cite_note-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup> </p><p>A 2006 study in northern Alaska found that day-living <a href="/wiki/Ground_squirrel" title="Ground squirrel">ground squirrels</a> and nocturnal <a href="/wiki/Porcupine" title="Porcupine">porcupines</a> strictly maintain their circadian rhythms through 82 days and nights of sunshine. The researchers speculate that these two rodents notice that the apparent distance between the sun and the horizon is shortest once a day, and thus have a sufficient signal to entrain (adjust) by.<sup id="cite_ref-54" class="reference"><a href="#cite_note-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Butterflies_and_moths">Butterflies and moths</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=8" title="Edit section: Butterflies and moths" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>The navigation of the fall migration of the <a href="/wiki/Monarch_butterfly" title="Monarch butterfly">Eastern North American monarch butterfly</a> (<i>Danaus plexippus</i>) to their overwintering grounds in central Mexico uses a time-compensated sun compass that depends upon a circadian clock in their antennae.<sup id="cite_ref-55" class="reference"><a href="#cite_note-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-56" class="reference"><a href="#cite_note-56"><span class="cite-bracket">[</span>56<span class="cite-bracket">]</span></a></sup> Circadian rhythm is also known to control mating behavioral in certain moth species such as <i><a href="/wiki/Spodoptera_littoralis" title="Spodoptera littoralis">Spodoptera littoralis</a></i>, where females produce specific <a href="/wiki/Pheromone" title="Pheromone">pheromone</a> that attracts and resets the male circadian rhythm to induce mating at night.<sup id="cite_ref-57" class="reference"><a href="#cite_note-57"><span class="cite-bracket">[</span>57<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(5)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="In_plants">In plants</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=9" title="Edit section: In plants" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-5 collapsible-block" id="mf-section-5"> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Jungpflanze_des_Seidenbaums_(Schlafbaum).png" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/cd/Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png/220px-Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png" decoding="async" width="220" height="161" class="mw-file-element" data-file-width="3892" data-file-height="2849"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 161px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/c/cd/Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png/220px-Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png" data-width="220" data-height="161" data-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/cd/Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png/330px-Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/cd/Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png/440px-Jungpflanze_des_Seidenbaums_%28Schlafbaum%29.png 2x" data-class="mw-file-element"> </span></a><figcaption>Sleeping tree by day and night</figcaption></figure> <p>Plant circadian rhythms tell the plant what season it is and when to flower for the best chance of attracting pollinators. Behaviors showing rhythms include leaf movement (<a href="/wiki/Nyctinasty" title="Nyctinasty">Nyctinasty</a>), growth, germination, stomatal/gas exchange, <a href="/wiki/Enzyme_activity" class="mw-redirect" title="Enzyme activity">enzyme activity</a>, <a href="/wiki/Photosynthesis" title="Photosynthesis">photosynthetic</a> activity, and fragrance emission, among others.<sup id="cite_ref-webb03_58-0" class="reference"><a href="#cite_note-webb03-58"><span class="cite-bracket">[</span>58<span class="cite-bracket">]</span></a></sup> Circadian rhythms occur as a plant entrains to synchronize with the light cycle of its surrounding environment. These rhythms are <a href="/wiki/Endogenous" class="mw-redirect" title="Endogenous">endogenously</a> generated, self-sustaining and are relatively constant over a range of ambient temperatures. Important features include two interacting <a href="/wiki/Transcription_translation_feedback_loop" title="Transcription translation feedback loop">transcription-translation feedback loops</a>: <a href="/wiki/Protein" title="Protein">proteins</a> containing PAS domains, which facilitate protein-protein interactions; and several photoreceptors that fine-tune the clock to different light conditions. Anticipation of changes in the environment allows appropriate changes in a plant's physiological state, conferring an adaptive advantage.<sup id="cite_ref-mcclung06_59-0" class="reference"><a href="#cite_note-mcclung06-59"><span class="cite-bracket">[</span>59<span class="cite-bracket">]</span></a></sup> A better understanding of plant circadian rhythms has applications in agriculture, such as helping farmers stagger crop harvests to extend crop availability and securing against massive losses due to weather. </p><p>Light is the signal by which plants synchronize their internal clocks to their environment and is sensed by a wide variety of photoreceptors. Red and blue light are absorbed through several <a href="/wiki/Phytochrome" title="Phytochrome">phytochromes</a> and <a href="/wiki/Cryptochrome" title="Cryptochrome">cryptochromes</a>. Phytochrome A, phyA, is light labile and allows germination and de-etiolation when light is scarce.<sup id="cite_ref-60" class="reference"><a href="#cite_note-60"><span class="cite-bracket">[</span>60<span class="cite-bracket">]</span></a></sup> Phytochromes B–E are more stable with phyB, the main phytochrome in seedlings grown in the light. The cryptochrome (cry) gene is also a light-sensitive component of the circadian clock and is thought to be involved both as a photoreceptor and as part of the clock's endogenous pacemaker mechanism. Cryptochromes 1–2 (involved in blue–UVA) help to maintain the period length in the clock through a whole range of light conditions.<sup id="cite_ref-webb03_58-1" class="reference"><a href="#cite_note-webb03-58"><span class="cite-bracket">[</span>58<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-mcclung06_59-1" class="reference"><a href="#cite_note-mcclung06-59"><span class="cite-bracket">[</span>59<span class="cite-bracket">]</span></a></sup> </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Data_on_circadian_rhythm_of_gene_expression_in_four_seedlings._Two_of_these_Arabidopsis_thaliana_seedlings_carry_a_firefly_luciferase_reporter_for_transcription_of_the_gene_CCA1_and_two_for_TOC1.png" class="mw-file-description"><noscript><img alt="Graph showing two pairs of rhythmic timeseries, peaking at alternating times of day, over six, 24-hour cycles." src="//upload.wikimedia.org/wikipedia/commons/thumb/0/07/Data_on_circadian_rhythm_of_gene_expression_in_four_seedlings._Two_of_these_Arabidopsis_thaliana_seedlings_carry_a_firefly_luciferase_reporter_for_transcription_of_the_gene_CCA1_and_two_for_TOC1.png/220px-thumbnail.png" decoding="async" width="220" height="147" class="mw-file-element" data-file-width="973" data-file-height="648"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 147px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/0/07/Data_on_circadian_rhythm_of_gene_expression_in_four_seedlings._Two_of_these_Arabidopsis_thaliana_seedlings_carry_a_firefly_luciferase_reporter_for_transcription_of_the_gene_CCA1_and_two_for_TOC1.png/220px-thumbnail.png" data-alt="Graph showing two pairs of rhythmic timeseries, peaking at alternating times of day, over six, 24-hour cycles." data-width="220" data-height="147" data-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/0/07/Data_on_circadian_rhythm_of_gene_expression_in_four_seedlings._Two_of_these_Arabidopsis_thaliana_seedlings_carry_a_firefly_luciferase_reporter_for_transcription_of_the_gene_CCA1_and_two_for_TOC1.png/330px-thumbnail.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/0/07/Data_on_circadian_rhythm_of_gene_expression_in_four_seedlings._Two_of_these_Arabidopsis_thaliana_seedlings_carry_a_firefly_luciferase_reporter_for_transcription_of_the_gene_CCA1_and_two_for_TOC1.png/440px-thumbnail.png 2x" data-class="mw-file-element"> </span></a><figcaption>Graph showing timeseries data from <a href="/wiki/Bioluminescence_imaging" title="Bioluminescence imaging">bioluminescence imaging</a> of circadian reporter genes. <a href="/wiki/Genetically_modified_organism" title="Genetically modified organism">Transgenic</a> seedlings of <i><a href="/wiki/Arabidopsis_thaliana" title="Arabidopsis thaliana">Arabidopsis thaliana</a></i> were imaged by a cooled <a href="/wiki/Charge-coupled_device" title="Charge-coupled device">CCD camera</a> under three cycles of 12h light: 12h dark followed by 3 days of constant light (from 96h). Their genomes carry firefly <a href="/wiki/Luciferase" title="Luciferase">luciferase</a> <a href="/wiki/Reporter_gene" title="Reporter gene">reporter genes</a> driven by the promoter sequences of clock genes. The signals of seedlings 61 (red) and 62 (blue) reflect transcription of the gene <a href="/wiki/Circadian_Clock_Associated_1" title="Circadian Clock Associated 1">CCA1</a>, peaking after lights-on (48h, 72h, etc.). Seedlings 64 (pale grey) and 65 (teal) reflect <a href="/wiki/TOC1_(gene)" title="TOC1 (gene)">TOC1</a>, peaking before lights-off (36h, 60h, etc.). The timeseries show 24-hour, circadian rhythms of gene expression in the living plants.</figcaption></figure> <p>The central oscillator generates a self-sustaining rhythm and is driven by two interacting feedback loops that are active at different times of day. The morning loop consists of <a href="/wiki/CCA1" class="mw-redirect" title="CCA1">CCA1</a> (Circadian and Clock-Associated 1) and <a href="/wiki/LHY" class="mw-redirect" title="LHY">LHY</a> (Late Elongated Hypocotyl), which encode closely related <a href="/wiki/MYB_(gene)" title="MYB (gene)">MYB transcription factors</a> that regulate circadian rhythms in <i>Arabidopsis</i>, as well as <a href="/wiki/Pseudo-response_regulator" title="Pseudo-response regulator">PRR 7 and 9</a> (Pseudo-Response Regulators.) The evening loop consists of GI (Gigantea) and ELF4, both involved in regulation of flowering time genes.<sup id="cite_ref-Mizoguchi_61-0" class="reference"><a href="#cite_note-Mizoguchi-61"><span class="cite-bracket">[</span>61<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-62" class="reference"><a href="#cite_note-62"><span class="cite-bracket">[</span>62<span class="cite-bracket">]</span></a></sup> When CCA1 and LHY are overexpressed (under constant light or dark conditions), plants become arrhythmic, and mRNA signals reduce, contributing to a <a href="/wiki/Negative_feedback" title="Negative feedback">negative feedback</a> loop. Gene expression of CCA1 and LHY oscillates and peaks in the early morning, whereas <a href="/wiki/TOC1_gene" class="mw-redirect" title="TOC1 gene">TOC1 gene</a> expression oscillates and peaks in the early evening. While it was previously hypothesised that these three genes model a negative feedback loop in which over-expressed CCA1 and LHY repress TOC1 and over-expressed TOC1 is a positive regulator of CCA1 and LHY,<sup id="cite_ref-mcclung06_59-2" class="reference"><a href="#cite_note-mcclung06-59"><span class="cite-bracket">[</span>59<span class="cite-bracket">]</span></a></sup> it was shown in 2012 by Andrew Millar and others that TOC1, in fact, serves as a repressor not only of CCA1, LHY, and PRR7 and 9 in the morning loop but also of GI and ELF4 in the evening loop. This finding and further computational modeling of <a href="/wiki/TOC1_gene" class="mw-redirect" title="TOC1 gene">TOC1 gene</a> functions and interactions suggest a reframing of the plant circadian clock as a triple negative-component <a href="/wiki/Repressilator" title="Repressilator">repressilator</a> model rather than the positive/negative-element feedback loop characterizing the clock in mammals.<sup id="cite_ref-63" class="reference"><a href="#cite_note-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> </p><p>In 2018, researchers found that the expression of PRR5 and TOC1 hnRNA nascent transcripts follows the same oscillatory pattern as processed mRNA transcripts rhythmically in <i>A. thaliana</i>. LNKs binds to the 5'region of PRR5 and TOC1 and interacts with RNAP II and other transcription factors. Moreover, RVE8-LNKs interaction enables a permissive histone-methylation pattern (H3K4me3) to be modified and the histone-modification itself parallels the oscillation of clock gene expression.<sup id="cite_ref-64" class="reference"><a href="#cite_note-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup> </p><p>It has previously been found that matching a plant's circadian rhythm to its external environment's light and dark cycles has the potential to positively affect the plant.<sup id="cite_ref-:02_65-0" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> Researchers came to this conclusion by performing experiments on three different varieties of <i><a href="/wiki/Arabidopsis_thaliana" title="Arabidopsis thaliana">Arabidopsis thaliana</a></i>. One of these varieties had a normal 24-hour circadian cycle.<sup id="cite_ref-:02_65-1" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> The other two varieties were mutated, one to have a circadian cycle of more than 27 hours, and one to have a shorter than normal circadian cycle of 20 hours.<sup id="cite_ref-:02_65-2" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> </p><p>The <i>Arabidopsis</i> with the 24-hour circadian cycle was grown in three different environments.<sup id="cite_ref-:02_65-3" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> One of these environments had a 20-hour light and dark cycle (10 hours of light and 10 hours of dark), the other had a 24-hour light and dark cycle (12 hours of light and 12 hours of dark),and the final environment had a 28-hour light and dark cycle (14 hours of light and 14 hours of dark).<sup id="cite_ref-:02_65-4" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> The two mutated plants were grown in both an environment that had a 20-hour light and dark cycle and in an environment that had a 28-hour light and dark cycle.<sup id="cite_ref-:02_65-5" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> It was found that the variety of <i>Arabidopsis</i> with a 24-hour circadian rhythm cycle grew best in an environment that also had a 24-hour light and dark cycle.<sup id="cite_ref-:02_65-6" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> Overall, it was found that all the varieties of <i>Arabidopsis thaliana</i> had greater levels of <a href="/wiki/Chlorophyll" title="Chlorophyll">chlorophyll</a> and increased growth in environments whose light and dark cycles matched their circadian rhythm.<sup id="cite_ref-:02_65-7" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> </p><p>Researchers suggested that a reason for this could be that matching an <i>Arabidopsis</i><span class="nowrap" style="padding-left:0.1em;">'s</span> circadian rhythm to its environment could allow the plant to be better prepared for dawn and dusk, and thus be able to better synchronize its processes.<sup id="cite_ref-:02_65-8" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> In this study, it was also found that the genes that help to control chlorophyll peaked a few hours after dawn.<sup id="cite_ref-:02_65-9" class="reference"><a href="#cite_note-:02-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> This appears to be consistent with the proposed phenomenon known as metabolic dawn.<sup id="cite_ref-:1_66-0" class="reference"><a href="#cite_note-:1-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup> </p><p>According to the metabolic dawn hypothesis, sugars produced by photosynthesis have potential to help regulate the circadian rhythm and certain photosynthetic and metabolic pathways.<sup id="cite_ref-:1_66-1" class="reference"><a href="#cite_note-:1-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-67" class="reference"><a href="#cite_note-67"><span class="cite-bracket">[</span>67<span class="cite-bracket">]</span></a></sup> As the sun rises, more light becomes available, which normally allows more photosynthesis to occur.<sup id="cite_ref-:1_66-2" class="reference"><a href="#cite_note-:1-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup> The sugars produced by photosynthesis repress PRR7.<sup id="cite_ref-:2_68-0" class="reference"><a href="#cite_note-:2-68"><span class="cite-bracket">[</span>68<span class="cite-bracket">]</span></a></sup> This repression of PRR7 then leads to the increased expression of CCA1.<sup id="cite_ref-:2_68-1" class="reference"><a href="#cite_note-:2-68"><span class="cite-bracket">[</span>68<span class="cite-bracket">]</span></a></sup> On the other hand, decreased photosynthetic sugar levels increase PRR7 expression and decrease CCA1 expression.<sup id="cite_ref-:1_66-3" class="reference"><a href="#cite_note-:1-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup> This feedback loop between CCA1 and PRR7 is what is proposed to cause metabolic dawn.<sup id="cite_ref-:1_66-4" class="reference"><a href="#cite_note-:1-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-69" class="reference"><a href="#cite_note-69"><span class="cite-bracket">[</span>69<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(6)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="In_Drosophila">In <i>Drosophila</i></h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=10" title="Edit section: In Drosophila" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-6 collapsible-block" id="mf-section-6"> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Drosophila_circadian_rhythm" title="Drosophila circadian rhythm">Drosophila circadian rhythm</a></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Drosophila_brains_and_the_circadian_system.jpg" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Drosophila_brains_and_the_circadian_system.jpg/220px-Drosophila_brains_and_the_circadian_system.jpg" decoding="async" width="220" height="360" class="mw-file-element" data-file-width="686" data-file-height="1124"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 360px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Drosophila_brains_and_the_circadian_system.jpg/220px-Drosophila_brains_and_the_circadian_system.jpg" data-width="220" data-height="360" data-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Drosophila_brains_and_the_circadian_system.jpg/330px-Drosophila_brains_and_the_circadian_system.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Drosophila_brains_and_the_circadian_system.jpg/440px-Drosophila_brains_and_the_circadian_system.jpg 2x" data-class="mw-file-element"> </span></a><figcaption>Key centers of the mammalian and <i>Drosophila</i> brains (A) and the circadian system in <i>Drosophila</i> (B)</figcaption></figure> <p>The molecular mechanism of circadian rhythm and light perception are best understood in <i>Drosophila</i>. Clock genes are discovered from <i>Drosophila</i>, and they act together with the clock neurones. There are two unique rhythms, one during the process of hatching (called <a href="/wiki/Eclosion" class="mw-redirect" title="Eclosion">eclosion</a>) from the pupa, and the other during mating.<sup id="cite_ref-70" class="reference"><a href="#cite_note-70"><span class="cite-bracket">[</span>70<span class="cite-bracket">]</span></a></sup> The clock neurones are located in distinct clusters in the central brain. The best-understood clock neurones are the large and small lateral ventral neurons (l-LNvs and s-LNvs) of the <a href="/wiki/Optic_lobe_(arthropods)" title="Optic lobe (arthropods)">optic lobe</a>. These neurones produce pigment dispersing factor (PDF), a neuropeptide that acts as a circadian neuromodulator between different clock neurones.<sup id="cite_ref-yoshi_71-0" class="reference"><a href="#cite_note-yoshi-71"><span class="cite-bracket">[</span>71<span class="cite-bracket">]</span></a></sup> </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Drosophila_circadian_rhythm.jpg" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/64/Drosophila_circadian_rhythm.jpg/220px-Drosophila_circadian_rhythm.jpg" decoding="async" width="220" height="165" class="mw-file-element" data-file-width="960" data-file-height="720"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 165px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/6/64/Drosophila_circadian_rhythm.jpg/220px-Drosophila_circadian_rhythm.jpg" data-width="220" data-height="165" data-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/64/Drosophila_circadian_rhythm.jpg/330px-Drosophila_circadian_rhythm.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/64/Drosophila_circadian_rhythm.jpg/440px-Drosophila_circadian_rhythm.jpg 2x" data-class="mw-file-element"> </span></a><figcaption>Molecular interactions of clock genes and proteins during <i>Drosophila</i> circadian rhythm</figcaption></figure> <p><i>Drosophila</i> circadian rhythm is through a transcription-translation feedback loop. The core clock mechanism consists of two interdependent feedback loops, namely the PER/TIM loop and the CLK/CYC loop.<sup id="cite_ref-72" class="reference"><a href="#cite_note-72"><span class="cite-bracket">[</span>72<span class="cite-bracket">]</span></a></sup> The CLK/CYC loop occurs during the day and initiates the transcription of the <i>per</i> and <i>tim</i> genes. But their proteins levels remain low until dusk, because during daylight also activates the <i>doubletime</i> (<i>dbt</i>) gene. DBT protein causes phosphorylation and turnover of monomeric PER proteins.<sup id="cite_ref-73" class="reference"><a href="#cite_note-73"><span class="cite-bracket">[</span>73<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-74" class="reference"><a href="#cite_note-74"><span class="cite-bracket">[</span>74<span class="cite-bracket">]</span></a></sup> TIM is also phosphorylated by shaggy until sunset. After sunset, DBT disappears, so that PER molecules stably bind to TIM. PER/TIM dimer enters the nucleus several at night, and binds to CLK/CYC dimers. Bound PER completely stops the transcriptional activity of CLK and CYC.<sup id="cite_ref-helfrich05_75-0" class="reference"><a href="#cite_note-helfrich05-75"><span class="cite-bracket">[</span>75<span class="cite-bracket">]</span></a></sup> </p><p>In the early morning, light activates the <i>cry</i> gene and its protein CRY causes the breakdown of TIM. Thus PER/TIM dimer dissociates, and the unbound PER becomes unstable. PER undergoes progressive phosphorylation and ultimately degradation. Absence of PER and TIM allows activation of <i>clk</i> and <i>cyc</i> genes. Thus, the clock is reset to start the next circadian cycle.<sup id="cite_ref-lalch_76-0" class="reference"><a href="#cite_note-lalch-76"><span class="cite-bracket">[</span>76<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="PER-TIM_model">PER-TIM model</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=11" title="Edit section: PER-TIM model" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>This protein model was developed based on the oscillations of the PER and TIM proteins in the <i>Drosophila</i>.<sup id="cite_ref-leloup_77-0" class="reference"><a href="#cite_note-leloup-77"><span class="cite-bracket">[</span>77<span class="cite-bracket">]</span></a></sup> It is based on its predecessor, the PER model where it was explained how the PER gene and its protein influence the biological clock.<sup id="cite_ref-gold1995_78-0" class="reference"><a href="#cite_note-gold1995-78"><span class="cite-bracket">[</span>78<span class="cite-bracket">]</span></a></sup> The model includes the formation of a nuclear PER-TIM complex which influences the transcription of the PER and the TIM genes (by providing negative feedback) and the multiple phosphorylation of these two proteins. The circadian oscillations of these two proteins seem to synchronise with the light-dark cycle even if they are not necessarily dependent on it.<sup id="cite_ref-gold2002_79-0" class="reference"><a href="#cite_note-gold2002-79"><span class="cite-bracket">[</span>79<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-leloup_77-1" class="reference"><a href="#cite_note-leloup-77"><span class="cite-bracket">[</span>77<span class="cite-bracket">]</span></a></sup> Both PER and TIM proteins are phosphorylated and after they form the PER-TIM nuclear complex they return inside the nucleus to stop the expression of the PER and TIM mRNA. This inhibition lasts as long as the protein, or the mRNA is not degraded.<sup id="cite_ref-leloup_77-2" class="reference"><a href="#cite_note-leloup-77"><span class="cite-bracket">[</span>77<span class="cite-bracket">]</span></a></sup> When this happens, the complex releases the inhibition. Here can also be mentioned that the degradation of the TIM protein is sped up by light.<sup id="cite_ref-gold2002_79-1" class="reference"><a href="#cite_note-gold2002-79"><span class="cite-bracket">[</span>79<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(7)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="In_mammals">In mammals</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=12" title="Edit section: In mammals" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-7 collapsible-block" id="mf-section-7"> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Circadian_rhythm_labeled.jpg" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/5/55/Circadian_rhythm_labeled.jpg/300px-Circadian_rhythm_labeled.jpg" decoding="async" width="300" height="200" class="mw-file-element" data-file-width="400" data-file-height="267"></noscript><span class="lazy-image-placeholder" style="width: 300px;height: 200px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/5/55/Circadian_rhythm_labeled.jpg/300px-Circadian_rhythm_labeled.jpg" data-width="300" data-height="200" data-srcset="//upload.wikimedia.org/wikipedia/commons/5/55/Circadian_rhythm_labeled.jpg 1.5x" data-class="mw-file-element"> </span></a><figcaption>A variation of an <a href="/wiki/Arnold_Eskin#Eskinogram" title="Arnold Eskin">eskinogram</a> illustrating the influence of light and darkness on circadian rhythms and related <a href="/wiki/Physiology" title="Physiology">physiology</a> and behavior through the <a href="/wiki/Suprachiasmatic_nucleus" title="Suprachiasmatic nucleus">suprachiasmatic nucleus</a> in humans</figcaption></figure> <p>The primary <a href="/wiki/Circadian_clock" title="Circadian clock">circadian clock</a> in <a href="/wiki/Mammal" title="Mammal">mammals</a> is located in the <a href="/wiki/Suprachiasmatic_nucleus" title="Suprachiasmatic nucleus">suprachiasmatic nucleus</a> (or nuclei) (SCN), a pair of distinct groups of <a href="/wiki/Cell_(biology)" title="Cell (biology)">cells</a> located in the <a href="/wiki/Hypothalamus" title="Hypothalamus">hypothalamus</a>. Destruction of the SCN results in the complete absence of a regular sleep–wake rhythm. The SCN receives information about illumination through the eyes. The <a href="/wiki/Retina" title="Retina">retina</a> of the eye contains "classical" <a href="/wiki/Photoreceptor_cell" title="Photoreceptor cell">photoreceptors</a> ("<a href="/wiki/Rod_cell" title="Rod cell">rods</a>" and "<a href="/wiki/Cone_cell" title="Cone cell">cones</a>"), which are used for conventional vision. But the retina also contains specialized <a href="/wiki/Photosensitive_ganglion_cell" class="mw-redirect" title="Photosensitive ganglion cell">ganglion cells</a> that are directly photosensitive, and project directly to the SCN, where they help in the entrainment (synchronization) of this master circadian clock. The proteins involved in the SCN clock are homologous to those found in the fruit fly.<sup id="cite_ref-HHMI-BioInteractive_80-0" class="reference"><a href="#cite_note-HHMI-BioInteractive-80"><span class="cite-bracket">[</span>80<span class="cite-bracket">]</span></a></sup> </p><p>These cells contain the photopigment <a href="/wiki/Melanopsin" title="Melanopsin">melanopsin</a> and their signals follow a pathway called the <a href="/wiki/Retinohypothalamic_tract" title="Retinohypothalamic tract">retinohypothalamic tract</a>, leading to the SCN. If cells from the SCN are removed and cultured, they maintain their own rhythm in the absence of external cues.<sup id="cite_ref-Welsh2010_81-0" class="reference"><a href="#cite_note-Welsh2010-81"><span class="cite-bracket">[</span>81<span class="cite-bracket">]</span></a></sup> </p><p>The SCN takes the information on the lengths of the day and night from the retina, interprets it, and passes it on to the <a href="/wiki/Pineal_gland" title="Pineal gland">pineal gland</a>, a tiny structure shaped like a <a href="/wiki/Pine_cone" class="mw-redirect" title="Pine cone">pine cone</a> and located on the <a href="/wiki/Epithalamus" title="Epithalamus">epithalamus</a>. In response, the pineal secretes the hormone <a href="/wiki/Melatonin" title="Melatonin">melatonin</a>.<sup id="cite_ref-82" class="reference"><a href="#cite_note-82"><span class="cite-bracket">[</span>82<span class="cite-bracket">]</span></a></sup> Secretion of melatonin peaks at night and ebbs during the day and its presence provides information about night-length. </p><p>Several studies have indicated that pineal melatonin feeds back on SCN rhythmicity to modulate circadian patterns of activity and other processes. However, the nature and system-level significance of this feedback are unknown.<sup id="cite_ref-83" class="reference"><a href="#cite_note-83"><span class="cite-bracket">[</span>83<span class="cite-bracket">]</span></a></sup> </p><p>The circadian rhythms of humans can be entrained to slightly shorter and longer periods than the Earth's 24 hours. Researchers at Harvard have shown that human subjects can at least be entrained to a 23.5-hour cycle and a 24.65-hour cycle.<sup id="cite_ref-84" class="reference"><a href="#cite_note-84"><span class="cite-bracket">[</span>84<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Humans">Humans</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=13" title="Edit section: Humans" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Circadian_rhythm.svg" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Circadian_rhythm.svg/300px-Circadian_rhythm.svg.png" decoding="async" width="300" height="225" class="mw-file-element" data-file-width="512" data-file-height="384"></noscript><span class="lazy-image-placeholder" style="width: 300px;height: 225px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Circadian_rhythm.svg/300px-Circadian_rhythm.svg.png" data-width="300" data-height="225" data-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Circadian_rhythm.svg/450px-Circadian_rhythm.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Circadian_rhythm.svg/600px-Circadian_rhythm.svg.png 2x" data-class="mw-file-element"> </span></a><figcaption>When eyes receive light from the sun, the pineal gland's production of melatonin is inhibited, and the hormones produced keep the human awake. When the eyes do not receive light, melatonin is produced in the pineal gland and the human becomes tired.</figcaption></figure> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/Sleep#Circadian_clock" title="Sleep">Sleep § Circadian clock</a>, and <a href="/wiki/Phase_response_curve#Light" title="Phase response curve">Phase response curve § Light</a></div> <p>Early research into circadian rhythms suggested that most people preferred a day closer to 25 hours when isolated from external stimuli like daylight and timekeeping. However, this research was faulty because it failed to shield the participants from artificial light. Although subjects were shielded from time cues (like clocks) and daylight, the researchers were not aware of the phase-delaying effects of indoor electric lights.<sup id="cite_ref-85" class="reference"><a href="#cite_note-85"><span class="cite-bracket">[</span>85<span class="cite-bracket">]</span></a></sup><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Accuracy_dispute#Disputed_statement" title="Wikipedia:Accuracy dispute"><span title="This is part review, part study, needs to be checked for proper use of secondary source (July 2014)">dubious</span></a> – <a href="/wiki/Talk:Circadian_rhythm#Dubious" title="Talk:Circadian rhythm">discuss</a></i>]</sup> The subjects were allowed to turn on light when they were awake and to turn it off when they wanted to sleep. Electric light in the evening delayed their circadian phase.<sup id="cite_ref-86" class="reference"><a href="#cite_note-86"><span class="cite-bracket">[</span>86<span class="cite-bracket">]</span></a></sup> A more stringent study conducted in 1999 by <a href="/wiki/Harvard_University" title="Harvard University">Harvard University</a> estimated the natural human rhythm to be closer to 24 hours and 11 minutes: much closer to the <a href="/wiki/Solar_time" title="Solar time">solar day</a>.<sup id="cite_ref-87" class="reference"><a href="#cite_note-87"><span class="cite-bracket">[</span>87<span class="cite-bracket">]</span></a></sup> Consistent with this research was a more recent study from 2010, which also identified sex differences, with the circadian period for women being slightly shorter (24.09 hours) than for men (24.19 hours).<sup id="cite_ref-:0_88-0" class="reference"><a href="#cite_note-:0-88"><span class="cite-bracket">[</span>88<span class="cite-bracket">]</span></a></sup> In this study, women tended to wake up earlier than men and exhibit a greater preference for morning activities than men, although the underlying biological mechanisms for these differences are unknown.<sup id="cite_ref-:0_88-1" class="reference"><a href="#cite_note-:0-88"><span class="cite-bracket">[</span>88<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Biological_markers_and_effects">Biological markers and effects</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=14" title="Edit section: Biological markers and effects" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>The classic phase markers for measuring the timing of a mammal's circadian rhythm are: </p> <ul><li><a href="/wiki/Melatonin" title="Melatonin">melatonin</a> secretion by the <a href="/wiki/Pineal_gland" title="Pineal gland">pineal gland</a>,<sup id="cite_ref-Benloucif_89-0" class="reference"><a href="#cite_note-Benloucif-89"><span class="cite-bracket">[</span>89<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Human_body_temperature" title="Human body temperature">core body temperature</a> minimum,<sup id="cite_ref-Benloucif_89-1" class="reference"><a href="#cite_note-Benloucif-89"><span class="cite-bracket">[</span>89<span class="cite-bracket">]</span></a></sup> and</li> <li>plasma level of <a href="/wiki/Cortisol" title="Cortisol">cortisol</a>.<sup id="cite_ref-pmid28578301_90-0" class="reference"><a href="#cite_note-pmid28578301-90"><span class="cite-bracket">[</span>90<span class="cite-bracket">]</span></a></sup></li></ul> <p>For temperature studies, subjects must remain awake but calm and semi-reclined in near darkness while their rectal temperatures are taken continuously. Though variation is great among normal <a href="/wiki/Chronotype" title="Chronotype">chronotypes</a>, the average human adult's temperature reaches its minimum at about 5:00 a.m., about two hours before habitual wake time. Baehr et al.<sup id="cite_ref-91" class="reference"><a href="#cite_note-91"><span class="cite-bracket">[</span>91<span class="cite-bracket">]</span></a></sup> found that, in young adults, the daily body temperature minimum occurred at about 04:00 (4 a.m.) for morning types, but at about 06:00 (6 a.m.) for evening types. This minimum occurred at approximately the middle of the eight-hour sleep period for morning types, but closer to waking in evening types. </p><p>Melatonin is absent from the system or undetectably low during daytime. Its onset in dim light, <i>dim-light melatonin onset</i> (DLMO), at roughly 21:00 (9 p.m.) can be measured in the blood or the saliva. Its major <a href="/wiki/Metabolite" title="Metabolite">metabolite</a> can also be measured in morning urine. Both DLMO and the midpoint (in time) of the presence of the hormone in the blood or saliva have been used as circadian markers. However, newer research indicates that the melatonin <i>offset</i> may be the more reliable marker. Benloucif et al.<sup id="cite_ref-Benloucif_89-2" class="reference"><a href="#cite_note-Benloucif-89"><span class="cite-bracket">[</span>89<span class="cite-bracket">]</span></a></sup> found that melatonin phase markers were more stable and more highly correlated with the timing of sleep than the core temperature minimum. They found that both sleep offset and melatonin offset are more strongly correlated with phase markers than the onset of sleep. In addition, the declining phase of the melatonin levels is more reliable and stable than the termination of melatonin synthesis. </p><p>Other physiological changes that occur according to a circadian rhythm include <a href="/wiki/Heart_rate" title="Heart rate">heart rate</a> and many cellular processes "including <a href="/wiki/Oxidative_stress" title="Oxidative stress">oxidative stress</a>, <a href="/wiki/Cell_metabolism" class="mw-redirect" title="Cell metabolism">cell metabolism</a>, immune and inflammatory responses,<sup id="cite_ref-92" class="reference"><a href="#cite_note-92"><span class="cite-bracket">[</span>92<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Epigenetics" title="Epigenetics">epigenetic</a> modification, <a href="/wiki/Hypoxia_(medical)" class="mw-redirect" title="Hypoxia (medical)">hypoxia</a>/<a href="/wiki/Hyperoxia" title="Hyperoxia">hyperoxia</a> response pathways, <a href="/wiki/Unfolded_protein_response" title="Unfolded protein response">endoplasmic reticular stress</a>, <a href="/wiki/Autophagy" title="Autophagy">autophagy</a>, and regulation of the <a href="/wiki/Stem_cell" title="Stem cell">stem cell</a> environment."<sup id="cite_ref-workshop_93-0" class="reference"><a href="#cite_note-workshop-93"><span class="cite-bracket">[</span>93<span class="cite-bracket">]</span></a></sup> In a study of young men, it was found that the heart rate reaches its lowest average rate during sleep, and its highest average rate shortly after waking.<sup id="cite_ref-HeartRate_94-0" class="reference"><a href="#cite_note-HeartRate-94"><span class="cite-bracket">[</span>94<span class="cite-bracket">]</span></a></sup> </p><p>In contradiction to previous studies, it has been found that there is no effect of body temperature on performance on psychological tests. This is likely due to evolutionary pressures for higher cognitive function compared to the other areas of function examined in previous studies.<sup id="cite_ref-95" class="reference"><a href="#cite_note-95"><span class="cite-bracket">[</span>95<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id='Outside_the_"master_clock"'><span id="Outside_the_.22master_clock.22"></span>Outside the "master clock"</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=15" title='Edit section: Outside the "master clock"' class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>More-or-less independent circadian rhythms are found in many organs and cells in the body outside the suprachiasmatic nuclei (SCN), the "master clock". Indeed, neuroscientist Joseph Takahashi and colleagues stated in a 2013 article that "almost every cell in the body contains a circadian clock".<sup id="cite_ref-96" class="reference"><a href="#cite_note-96"><span class="cite-bracket">[</span>96<span class="cite-bracket">]</span></a></sup> For example, these clocks, called peripheral oscillators, have been found in the adrenal gland, <a href="/wiki/Oesophagus" class="mw-redirect" title="Oesophagus">oesophagus</a>, <a href="/wiki/Lungs" class="mw-redirect" title="Lungs">lungs</a>, <a href="/wiki/Liver" title="Liver">liver</a>, <a href="/wiki/Pancreas" title="Pancreas">pancreas</a>, <a href="/wiki/Spleen" title="Spleen">spleen</a>, <a href="/wiki/Thymus" title="Thymus">thymus</a>, and skin.<sup id="cite_ref-97" class="reference"><a href="#cite_note-97"><span class="cite-bracket">[</span>97<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-98" class="reference"><a href="#cite_note-98"><span class="cite-bracket">[</span>98<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-99" class="reference"><a href="#cite_note-99"><span class="cite-bracket">[</span>99<span class="cite-bracket">]</span></a></sup> There is also some evidence that the olfactory bulb<sup id="cite_ref-100" class="reference"><a href="#cite_note-100"><span class="cite-bracket">[</span>100<span class="cite-bracket">]</span></a></sup> and prostate<sup id="cite_ref-101" class="reference"><a href="#cite_note-101"><span class="cite-bracket">[</span>101<span class="cite-bracket">]</span></a></sup> may experience oscillations, at least when cultured. </p><p>Though oscillators in the skin respond to light, a systemic influence has not been proven.<sup id="cite_ref-102" class="reference"><a href="#cite_note-102"><span class="cite-bracket">[</span>102<span class="cite-bracket">]</span></a></sup> In addition, many oscillators, such as <a href="/wiki/Liver_cells" class="mw-redirect" title="Liver cells">liver cells</a>, for example, have been shown to respond to inputs other than light, such as feeding.<sup id="cite_ref-103" class="reference"><a href="#cite_note-103"><span class="cite-bracket">[</span>103<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(8)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="Light_and_the_biological_clock">Light and the biological clock</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=16" title="Edit section: Light and the biological clock" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-8 collapsible-block" id="mf-section-8"> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Further information: <a href="/wiki/Light_effects_on_circadian_rhythm" title="Light effects on circadian rhythm">Light effects on circadian rhythm</a></div> <p>Light resets the biological clock in accordance with the <a href="/wiki/Phase_response_curve" title="Phase response curve">phase response curve</a> (PRC). Depending on the timing, light can advance or delay the circadian rhythm. Both the PRC and the required <a href="/wiki/Illuminance" title="Illuminance">illuminance</a> vary from species to species, and lower light levels are required to reset the clocks in <a href="/wiki/Nocturnality" title="Nocturnality">nocturnal</a> rodents than in humans.<sup id="cite_ref-104" class="reference"><a href="#cite_note-104"><span class="cite-bracket">[</span>104<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(9)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="Enforced_longer_or_shorter_cycles">Enforced longer or shorter cycles</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=17" title="Edit section: Enforced longer or shorter cycles" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-9 collapsible-block" id="mf-section-9"> <p>Various studies on humans have made use of enforced sleep/wake cycles strongly different from 24 hours, such as those conducted by <a href="/wiki/Nathaniel_Kleitman" title="Nathaniel Kleitman">Nathaniel Kleitman</a> in 1938 (28 hours) and <a href="/wiki/Derk-Jan_Dijk" title="Derk-Jan Dijk">Derk-Jan Dijk</a> and <a href="/wiki/Charles_Czeisler" title="Charles Czeisler">Charles Czeisler</a> in the 1990s (20 hours). Because people with a normal (typical) <a href="/wiki/Circadian_clock" title="Circadian clock">circadian clock</a> cannot entrain to such abnormal day/night rhythms,<sup id="cite_ref-105" class="reference"><a href="#cite_note-105"><span class="cite-bracket">[</span>105<span class="cite-bracket">]</span></a></sup> this is referred to as a forced desynchrony protocol. Under such a protocol, sleep and wake episodes are uncoupled from the body's endogenous circadian period, which allows researchers to assess the effects of circadian phase (i.e., the relative timing of the circadian cycle) on aspects of sleep and wakefulness including <a href="/wiki/Sleep_latency" class="mw-redirect" title="Sleep latency">sleep latency</a> and other functions - both physiological, behavioral, and cognitive.<sup id="cite_ref-106" class="reference"><a href="#cite_note-106"><span class="cite-bracket">[</span>106<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-107" class="reference"><a href="#cite_note-107"><span class="cite-bracket">[</span>107<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-108" class="reference"><a href="#cite_note-108"><span class="cite-bracket">[</span>108<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-109" class="reference"><a href="#cite_note-109"><span class="cite-bracket">[</span>109<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-110" class="reference"><a href="#cite_note-110"><span class="cite-bracket">[</span>110<span class="cite-bracket">]</span></a></sup> </p><p>Studies also show that <i><a href="/wiki/Cyclosa_turbinata" title="Cyclosa turbinata">Cyclosa turbinata</a></i> is unique in that its locomotor and web-building activity cause it to have an exceptionally short-period circadian clock, about 19 hours. When <i>C. turbinata</i> spiders are placed into chambers with periods of 19, 24, or 29 hours of evenly split light and dark, none of the spiders exhibited decreased longevity in their own circadian clock. These findings suggest that <i>C. turbinata</i> do not have the same costs of extreme desynchronization as do other species of animals. </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(10)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="Human_health">Human health</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=18" title="Edit section: Human health" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-10 collapsible-block" id="mf-section-10"> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Day_Sleepers_crop.jpg" class="mw-file-description"><noscript><img src="//upload.wikimedia.org/wikipedia/commons/thumb/0/0a/Day_Sleepers_crop.jpg/220px-Day_Sleepers_crop.jpg" decoding="async" width="220" height="129" class="mw-file-element" data-file-width="851" data-file-height="499"></noscript><span class="lazy-image-placeholder" style="width: 220px;height: 129px;" data-mw-src="//upload.wikimedia.org/wikipedia/commons/thumb/0/0a/Day_Sleepers_crop.jpg/220px-Day_Sleepers_crop.jpg" data-width="220" data-height="129" data-srcset="//upload.wikimedia.org/wikipedia/commons/thumb/0/0a/Day_Sleepers_crop.jpg/330px-Day_Sleepers_crop.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/0/0a/Day_Sleepers_crop.jpg/440px-Day_Sleepers_crop.jpg 2x" data-class="mw-file-element"> </span></a><figcaption>A short nap during the day does not affect circadian rhythms.</figcaption></figure> <div class="mw-heading mw-heading3"><h3 id="Foundation_of_circadian_medicine">Foundation of circadian medicine</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=19" title="Edit section: Foundation of circadian medicine" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>The leading edge of circadian biology research is translation of basic body clock mechanisms into clinical tools, and this is especially relevant to the treatment of cardiovascular disease.<sup id="cite_ref-pubmed.ncbi.nlm.nih.gov_111-0" class="reference"><a href="#cite_note-pubmed.ncbi.nlm.nih.gov-111"><span class="cite-bracket">[</span>111<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-112" class="reference"><a href="#cite_note-112"><span class="cite-bracket">[</span>112<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-113" class="reference"><a href="#cite_note-113"><span class="cite-bracket">[</span>113<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-114" class="reference"><a href="#cite_note-114"><span class="cite-bracket">[</span>114<span class="cite-bracket">]</span></a></sup> Timing of medical treatment in coordination with the body clock, <a href="/wiki/Chronotherapy_(treatment_scheduling)" title="Chronotherapy (treatment scheduling)">chronotherapeutics</a>, may also benefit patients with hypertension (high blood pressure) by significantly increasing efficacy and reduce drug toxicity or adverse reactions.<sup id="cite_ref-115" class="reference"><a href="#cite_note-115"><span class="cite-bracket">[</span>115<span class="cite-bracket">]</span></a></sup> 3) "Circadian Pharmacology" or drugs targeting the circadian clock mechanism have been shown experimentally in rodent models to significantly reduce the damage due to heart attacks and prevent heart failure.<sup id="cite_ref-116" class="reference"><a href="#cite_note-116"><span class="cite-bracket">[</span>116<span class="cite-bracket">]</span></a></sup> Importantly, for rational translation of the most promising Circadian Medicine therapies to clinical practice, it is imperative that we understand how it helps treat disease in both biological sexes.<sup id="cite_ref-117" class="reference"><a href="#cite_note-117"><span class="cite-bracket">[</span>117<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-118" class="reference"><a href="#cite_note-118"><span class="cite-bracket">[</span>118<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-119" class="reference"><a href="#cite_note-119"><span class="cite-bracket">[</span>119<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-120" class="reference"><a href="#cite_note-120"><span class="cite-bracket">[</span>120<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Causes_of_disruption_to_circadian_rhythms">Causes of disruption to circadian rhythms</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=20" title="Edit section: Causes of disruption to circadian rhythms" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <div class="mw-heading mw-heading4"><h4 id="Indoor_lighting">Indoor lighting</h4><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=21" title="Edit section: Indoor lighting" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>Lighting requirements for circadian regulation are not simply the same as those for vision; planning of indoor lighting in offices and institutions is beginning to take this into account.<sup id="cite_ref-121" class="reference"><a href="#cite_note-121"><span class="cite-bracket">[</span>121<span class="cite-bracket">]</span></a></sup> Animal studies on the effects of light in laboratory conditions have until recently considered light intensity (<a href="/wiki/Irradiance" title="Irradiance">irradiance</a>) but not color, which can be shown to "act as an essential regulator of biological timing in more natural settings".<sup id="cite_ref-122" class="reference"><a href="#cite_note-122"><span class="cite-bracket">[</span>122<span class="cite-bracket">]</span></a></sup> </p><p>Blue LED lighting suppresses <a href="/wiki/Melatonin" title="Melatonin">melatonin</a> production five times more than the orange-yellow <a href="/wiki/Sodium-vapor_lamp" title="Sodium-vapor lamp">high-pressure sodium (HPS) light</a>; a <a href="/wiki/Metal_halide_lamp" class="mw-redirect" title="Metal halide lamp">metal halide lamp</a>, which is white light, suppresses melatonin at a rate more than three times greater than HPS.<sup id="cite_ref-123" class="reference"><a href="#cite_note-123"><span class="cite-bracket">[</span>123<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Biology_of_depression#Circadian_rhythm" title="Biology of depression">Depression symptoms</a> from long term nighttime light exposure can be undone by returning to a normal cycle.<sup id="cite_ref-124" class="reference"><a href="#cite_note-124"><span class="cite-bracket">[</span>124<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Airline_pilots_and_cabin_crew">Airline pilots and cabin crew</h4><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=22" title="Edit section: Airline pilots and cabin crew" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>Due to the nature of work of airline pilots, who often cross several time zones and regions of sunlight and darkness in one day, and spend many hours awake both day and night, they are often unable to maintain sleep patterns that correspond to the natural human circadian rhythm; this situation can easily lead to <a href="/wiki/Fatigue_(physical)" class="mw-redirect" title="Fatigue (physical)">fatigue</a>. The <a href="/wiki/NTSB" class="mw-redirect" title="NTSB">NTSB</a> cites this as contributing to many accidents,<sup id="cite_ref-125" class="reference"><a href="#cite_note-125"><span class="cite-bracket">[</span>125<span class="cite-bracket">]</span></a></sup> and has conducted several research studies in order to find methods of combating fatigue in pilots.<sup id="cite_ref-126" class="reference"><a href="#cite_note-126"><span class="cite-bracket">[</span>126<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Effect_of_drugs">Effect of drugs</h4><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=23" title="Edit section: Effect of drugs" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>Studies conducted on both animals and humans show major bidirectional relationships between the circadian system and abusive drugs. It is indicated that these abusive drugs affect the central circadian pacemaker. Individuals with substance use disorder display disrupted rhythms. These disrupted rhythms can increase the risk for substance abuse and relapse. It is possible that genetic and/or environmental disturbances to the normal sleep and wake cycle can increase the susceptibility to addiction.<sup id="cite_ref-Logan_127-0" class="reference"><a href="#cite_note-Logan-127"><span class="cite-bracket">[</span>127<span class="cite-bracket">]</span></a></sup> </p><p>It is difficult to determine if a disturbance in the circadian rhythm is at fault for an increase in prevalence for substance abuse—or if other environmental factors such as stress are to blame. Changes to the circadian rhythm and sleep occur once an individual begins abusing drugs and alcohol. Once an individual stops using drugs and alcohol, the circadian rhythm continues to be disrupted.<sup id="cite_ref-Logan_127-1" class="reference"><a href="#cite_note-Logan-127"><span class="cite-bracket">[</span>127<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Alcohol_(drug)" title="Alcohol (drug)">Alcohol</a> consumption disrupts circadian rhythms, with acute intake causing dose-dependent alterations in melatonin and cortisol levels, as well as core body temperature, which normalize the following morning, while chronic alcohol use leads to more severe and persistent disruptions that are associated with alcohol use disorders (AUD) and withdrawal symptoms.<sup id="cite_ref-128" class="reference"><a href="#cite_note-128"><span class="cite-bracket">[</span>128<span class="cite-bracket">]</span></a></sup> </p><p>The stabilization of sleep and the circadian rhythm might possibly help to reduce the vulnerability to addiction and reduce the chances of relapse.<sup id="cite_ref-Logan_127-2" class="reference"><a href="#cite_note-Logan-127"><span class="cite-bracket">[</span>127<span class="cite-bracket">]</span></a></sup> </p><p>Circadian rhythms and <a href="/wiki/CLOCK" title="CLOCK">clock</a> genes expressed in brain regions outside the <a href="/wiki/Suprachiasmatic_nucleus" title="Suprachiasmatic nucleus">suprachiasmatic nucleus</a> may significantly influence the effects produced by drugs such as <a href="/wiki/Cocaine" title="Cocaine">cocaine</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (November 2013)">citation needed</span></a></i>]</sup> Moreover, genetic manipulations of clock genes profoundly affect cocaine's actions.<sup id="cite_ref-129" class="reference"><a href="#cite_note-129"><span class="cite-bracket">[</span>129<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Consequences_of_disruption_to_circadian_rhythms">Consequences of disruption to circadian rhythms</h3><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=24" title="Edit section: Consequences of disruption to circadian rhythms" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <div class="mw-heading mw-heading4"><h4 id="Disruption">Disruption</h4><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=25" title="Edit section: Disruption" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Further information: <a href="/wiki/Circadian_rhythm_sleep_disorder" title="Circadian rhythm sleep disorder">Circadian rhythm sleep disorder</a></div> <p>Disruption to rhythms usually has a negative effect. Many travelers have experienced the condition known as <a href="/wiki/Jet_lag" title="Jet lag">jet lag</a>, with its associated symptoms of <a href="/wiki/Fatigue_(physical)" class="mw-redirect" title="Fatigue (physical)">fatigue</a>, <a href="/wiki/Disorientation" class="mw-redirect" title="Disorientation">disorientation</a> and <a href="/wiki/Insomnia" title="Insomnia">insomnia</a>.<sup id="cite_ref-130" class="reference"><a href="#cite_note-130"><span class="cite-bracket">[</span>130<span class="cite-bracket">]</span></a></sup> </p><p>A number of other disorders, such as <a href="/wiki/Bipolar_disorder" title="Bipolar disorder">bipolar disorder</a>, <a href="/wiki/Major_depressive_disorder" title="Major depressive disorder">depression</a>, and some <a href="/wiki/Sleep_disorder" title="Sleep disorder">sleep disorders</a> such as <a href="/wiki/Delayed_sleep_phase_disorder" title="Delayed sleep phase disorder">delayed sleep phase disorder</a> (DSPD), are associated with irregular or pathological functioning of circadian rhythms.<sup id="cite_ref-131" class="reference"><a href="#cite_note-131"><span class="cite-bracket">[</span>131<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-132" class="reference"><a href="#cite_note-132"><span class="cite-bracket">[</span>132<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-133" class="reference"><a href="#cite_note-133"><span class="cite-bracket">[</span>133<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-134" class="reference"><a href="#cite_note-134"><span class="cite-bracket">[</span>134<span class="cite-bracket">]</span></a></sup> </p><p>Disruption to rhythms in the longer term is believed to have significant adverse health consequences for peripheral organs outside the brain, in particular in the development or exacerbation of cardiovascular disease.<sup id="cite_ref-Zelinski2014_135-0" class="reference"><a href="#cite_note-Zelinski2014-135"><span class="cite-bracket">[</span>135<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-136" class="reference"><a href="#cite_note-136"><span class="cite-bracket">[</span>136<span class="cite-bracket">]</span></a></sup> </p><p>Studies have shown that maintaining normal sleep and circadian rhythms is important for many aspects of brain and health.<sup id="cite_ref-Zelinski2014_135-1" class="reference"><a href="#cite_note-Zelinski2014-135"><span class="cite-bracket">[</span>135<span class="cite-bracket">]</span></a></sup> A number of studies have also indicated that a <a href="/wiki/Power-nap" class="mw-redirect" title="Power-nap">power-nap</a>, a short period of sleep during the day, can reduce stress and may improve productivity without any measurable effect on normal circadian rhythms.<sup id="cite_ref-137" class="reference"><a href="#cite_note-137"><span class="cite-bracket">[</span>137<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-138" class="reference"><a href="#cite_note-138"><span class="cite-bracket">[</span>138<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-139" class="reference"><a href="#cite_note-139"><span class="cite-bracket">[</span>139<span class="cite-bracket">]</span></a></sup> Circadian rhythms also play a part in the <a href="/wiki/Reticular_activating_system" class="mw-redirect" title="Reticular activating system">reticular activating system</a>, which is crucial for maintaining a state of consciousness. A reversal<sup class="noprint Inline-Template" style="margin-left:0.1em; white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Please_clarify" title="Wikipedia:Please clarify"><span title="The text near this tag may need clarification or removal of jargon. (April 2019)">clarification needed</span></a></i>]</sup> in the sleep–wake cycle may be a sign or complication of <a href="/wiki/Uremia" title="Uremia">uremia</a>,<sup id="cite_ref-140" class="reference"><a href="#cite_note-140"><span class="cite-bracket">[</span>140<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Azotemia" title="Azotemia">azotemia</a> or <a href="/wiki/Acute_kidney_injury" title="Acute kidney injury">acute kidney injury</a>.<sup id="cite_ref-141" class="reference"><a href="#cite_note-141"><span class="cite-bracket">[</span>141<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-142" class="reference"><a href="#cite_note-142"><span class="cite-bracket">[</span>142<span class="cite-bracket">]</span></a></sup> Studies have also helped elucidate how light has a <a href="/wiki/Light_effects_on_circadian_rhythm" title="Light effects on circadian rhythm">direct effect</a> on human health through its influence on the circadian biology.<sup id="cite_ref-143" class="reference"><a href="#cite_note-143"><span class="cite-bracket">[</span>143<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Relationship_with_cardiovascular_disease">Relationship with cardiovascular disease</h4><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=26" title="Edit section: Relationship with cardiovascular disease" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>One of the first studies to determine how disruption of circadian rhythms causes cardiovascular disease was performed in the Tau hamsters, which have a genetic defect in their circadian clock mechanism.<sup id="cite_ref-Circadian_rhythm_disorganization_pr_144-0" class="reference"><a href="#cite_note-Circadian_rhythm_disorganization_pr-144"><span class="cite-bracket">[</span>144<span class="cite-bracket">]</span></a></sup> When maintained in a 24-hour light-dark cycle that was "out of sync" with their normal 22 circadian mechanism they developed profound cardiovascular and renal disease; however, when the Tau animals were raised for their entire lifespan on a 22-hour daily light-dark cycle they had a healthy cardiovascular system.<sup id="cite_ref-Circadian_rhythm_disorganization_pr_144-1" class="reference"><a href="#cite_note-Circadian_rhythm_disorganization_pr-144"><span class="cite-bracket">[</span>144<span class="cite-bracket">]</span></a></sup> The adverse effects of circadian misalignment on human physiology has been studied in the laboratory using a misalignment protocol,<sup id="cite_ref-145" class="reference"><a href="#cite_note-145"><span class="cite-bracket">[</span>145<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-146" class="reference"><a href="#cite_note-146"><span class="cite-bracket">[</span>146<span class="cite-bracket">]</span></a></sup> and by studying shift workers.<sup id="cite_ref-pubmed.ncbi.nlm.nih.gov_111-1" class="reference"><a href="#cite_note-pubmed.ncbi.nlm.nih.gov-111"><span class="cite-bracket">[</span>111<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-147" class="reference"><a href="#cite_note-147"><span class="cite-bracket">[</span>147<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Kervezee_396–412_148-0" class="reference"><a href="#cite_note-Kervezee_396%E2%80%93412-148"><span class="cite-bracket">[</span>148<span class="cite-bracket">]</span></a></sup> Circadian misalignment is associated with many risk factors of cardiovascular disease. High levels of the atherosclerosis biomarker, resistin, have been reported in shift workers indicating the link between circadian misalignment and plaque build up in arteries.<sup id="cite_ref-Kervezee_396–412_148-1" class="reference"><a href="#cite_note-Kervezee_396%E2%80%93412-148"><span class="cite-bracket">[</span>148<span class="cite-bracket">]</span></a></sup> Additionally, elevated triacylglyceride levels (molecules used to store excess fatty acids) were observed and contribute to the hardening of arteries, which is associated with cardiovascular diseases including heart attack, stroke and heart disease.<sup id="cite_ref-Kervezee_396–412_148-2" class="reference"><a href="#cite_note-Kervezee_396%E2%80%93412-148"><span class="cite-bracket">[</span>148<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Proper_e147–e157_149-0" class="reference"><a href="#cite_note-Proper_e147%E2%80%93e157-149"><span class="cite-bracket">[</span>149<span class="cite-bracket">]</span></a></sup> Shift work and the resulting circadian misalignment is also associated with hypertension.<sup id="cite_ref-pmid22211891_150-0" class="reference"><a href="#cite_note-pmid22211891-150"><span class="cite-bracket">[</span>150<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Obesity_and_diabetes">Obesity and diabetes</h4><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=27" title="Edit section: Obesity and diabetes" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p><a href="/wiki/Obesity" title="Obesity">Obesity</a> and <a href="/wiki/Diabetes" title="Diabetes">diabetes</a> are associated with lifestyle and genetic factors. Among those factors, disruption of the circadian clockwork and/or misalignment of the circadian timing system with the external environment (e.g., light–dark cycle) can play a role in the development of metabolic disorders.<sup id="cite_ref-Zelinski2014_135-2" class="reference"><a href="#cite_note-Zelinski2014-135"><span class="cite-bracket">[</span>135<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Shift_work" title="Shift work">Shift work</a> or chronic <a href="/wiki/Jet_lag" title="Jet lag">jet lag</a> have profound consequences for circadian and metabolic events in the body. Animals that are forced to eat during their resting period show increased body mass and altered expression of clock and metabolic genes.<sup id="cite_ref-151" class="reference"><a href="#cite_note-151"><span class="cite-bracket">[</span>151<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Proper_e147–e157_149-1" class="reference"><a href="#cite_note-Proper_e147%E2%80%93e157-149"><span class="cite-bracket">[</span>149<span class="cite-bracket">]</span></a></sup> In humans, shift work that favours irregular eating times is associated with altered insulin sensitivity, diabetes and higher body mass.<sup id="cite_ref-pmid22211891_150-1" class="reference"><a href="#cite_note-pmid22211891-150"><span class="cite-bracket">[</span>150<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Proper_e147–e157_149-2" class="reference"><a href="#cite_note-Proper_e147%E2%80%93e157-149"><span class="cite-bracket">[</span>149<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-152" class="reference"><a href="#cite_note-152"><span class="cite-bracket">[</span>152<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Cognitive_effects">Cognitive effects</h4><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=28" title="Edit section: Cognitive effects" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div> <p>Reduced cognitive function has been associated with circadian misalignment. Chronic shift workers display increased rates of operational error, impaired visual-motor performance and processing efficacy which can lead to both a reduction in performance and potential safety issues.<sup id="cite_ref-153" class="reference"><a href="#cite_note-153"><span class="cite-bracket">[</span>153<span class="cite-bracket">]</span></a></sup> Increased risk of dementia is associated with chronic night shift workers compared to day shift workers, particularly for individuals over 50 years old.<sup id="cite_ref-154" class="reference"><a href="#cite_note-154"><span class="cite-bracket">[</span>154<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-155" class="reference"><a href="#cite_note-155"><span class="cite-bracket">[</span>155<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-156" class="reference"><a href="#cite_note-156"><span class="cite-bracket">[</span>156<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(11)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="Society_and_culture">Society and culture</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=29" title="Edit section: Society and culture" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-11 collapsible-block" id="mf-section-11"> <p>In 2017, <a href="/wiki/Jeffrey_C._Hall" title="Jeffrey C. Hall">Jeffrey C. Hall</a>, <a href="/wiki/Michael_W._Young" title="Michael W. Young">Michael W. Young</a>, and <a href="/wiki/Michael_Rosbash" title="Michael Rosbash">Michael Rosbash</a> were awarded <a href="/wiki/Nobel_Prize_in_Physiology_or_Medicine" title="Nobel Prize in Physiology or Medicine">Nobel Prize in Physiology or Medicine</a> "for their discoveries of molecular mechanisms controlling the circadian rhythm".<sup id="cite_ref-157" class="reference"><a href="#cite_note-157"><span class="cite-bracket">[</span>157<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Nobel_Press_Release_158-0" class="reference"><a href="#cite_note-Nobel_Press_Release-158"><span class="cite-bracket">[</span>158<span class="cite-bracket">]</span></a></sup> </p><p>Circadian rhythms was taken as an example of scientific knowledge being transferred into the public sphere.<sup id="cite_ref-159" class="reference"><a href="#cite_note-159"><span class="cite-bracket">[</span>159<span class="cite-bracket">]</span></a></sup> </p> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(12)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="See_also">See also</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=30" title="Edit section: See also" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-12 collapsible-block" id="mf-section-12"> <style data-mw-deduplicate="TemplateStyles:r1184024115">.mw-parser-output .div-col{margin-top:0.3em;column-width:30em}.mw-parser-output .div-col-small{font-size:90%}.mw-parser-output .div-col-rules{column-rule:1px solid #aaa}.mw-parser-output .div-col dl,.mw-parser-output .div-col ol,.mw-parser-output .div-col ul{margin-top:0}.mw-parser-output .div-col li,.mw-parser-output .div-col dd{page-break-inside:avoid;break-inside:avoid-column}</style><div class="div-col"> <ul><li><a href="/wiki/Actigraphy" title="Actigraphy">Actigraphy</a> (also known as actimetry)</li> <li><a href="/wiki/ARNTL" class="mw-redirect" title="ARNTL">ARNTL</a></li> <li><a href="/wiki/ARNTL2" title="ARNTL2">ARNTL2</a></li> <li><a href="/wiki/Bacterial_circadian_rhythms" class="mw-redirect" title="Bacterial circadian rhythms">Bacterial circadian rhythms</a></li> <li><a href="/wiki/Circadian_rhythm_sleep_disorders" class="mw-redirect" title="Circadian rhythm sleep disorders">Circadian rhythm sleep disorders</a>, such as <ul><li><a href="/wiki/Advanced_sleep_phase_disorder" title="Advanced sleep phase disorder">Advanced sleep phase disorder</a></li> <li><a href="/wiki/Delayed_sleep_phase_disorder" title="Delayed sleep phase disorder">Delayed sleep phase disorder</a></li> <li><a href="/wiki/Non-24-hour_sleep%E2%80%93wake_disorder" title="Non-24-hour sleep–wake disorder">Non-24-hour sleep–wake disorder</a></li></ul></li> <li><a href="/wiki/Chronobiology" title="Chronobiology">Chronobiology</a></li> <li><a href="/wiki/Chronodisruption" title="Chronodisruption">Chronodisruption</a></li> <li><a href="/wiki/CLOCK" title="CLOCK">CLOCK</a></li> <li><a href="/wiki/Circasemidian_rhythm" title="Circasemidian rhythm">Circasemidian rhythm</a></li> <li><a href="/wiki/Circaseptan" title="Circaseptan">Circaseptan</a>, 7-day biological cycle</li> <li><a href="/wiki/Cryptochrome" title="Cryptochrome">Cryptochrome</a></li> <li><a href="/wiki/CRY1" class="mw-redirect" title="CRY1">CRY1</a> and <a href="/wiki/CRY2" class="mw-redirect" title="CRY2">CRY2</a>: the cryptochrome family genes</li> <li><a href="/wiki/Diurnal_cycle" title="Diurnal cycle">Diurnal cycle</a></li> <li><a href="/wiki/Light_effects_on_circadian_rhythm" title="Light effects on circadian rhythm">Light effects on circadian rhythm</a></li> <li><a href="/wiki/Light_in_school_buildings" title="Light in school buildings">Light in school buildings</a></li> <li><a href="/wiki/PER1" class="mw-redirect" title="PER1">PER1</a>, <a href="/wiki/PER2" title="PER2">PER2</a>, and <a href="/wiki/PER3" title="PER3">PER3</a>: the period family genes</li> <li><a href="/wiki/Photosensitive_ganglion_cell" class="mw-redirect" title="Photosensitive ganglion cell">Photosensitive ganglion cell</a>: part of the eye which is involved in regulating circadian rhythm.</li> <li><a href="/wiki/Polyphasic_sleep" title="Polyphasic sleep">Polyphasic sleep</a></li> <li><a href="/wiki/Rev-ErbA_alpha" title="Rev-ErbA alpha">Rev-ErbA alpha</a></li> <li><a href="/wiki/Segmented_sleep" class="mw-redirect" title="Segmented sleep">Segmented sleep</a></li> <li><a href="/wiki/Sleep_architecture" class="mw-redirect" title="Sleep architecture">Sleep architecture</a> (sleep in humans)</li> <li><a href="/wiki/Sleep_in_non-human_animals" class="mw-redirect" title="Sleep in non-human animals">Sleep in non-human animals</a></li> <li><a href="/wiki/Stefania_Follini" title="Stefania Follini">Stefania Follini</a></li> <li><a href="/wiki/Ultradian_rhythm" title="Ultradian rhythm">Ultradian rhythm</a></li></ul> </div> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(13)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 id="References">References</h2><span class="mw-editsection"> <a role="button" href="/w/index.php?title=Circadian_rhythm&action=edit&section=31" title="Edit section: References" class="cdx-button cdx-button--size-large cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--icon-only cdx-button--weight-quiet "> <span class="minerva-icon minerva-icon--edit"></span> <span>edit</span> </a> </span> </div><section class="mf-section-13 collapsible-block" id="mf-section-13"> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 32em;"> <ol class="references"> <li id="cite_note-Edgar_459–464-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-Edgar_459%E2%80%93464_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Edgar_459%E2%80%93464_1-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFEdgarGreenZhaovan_Ooijen2012" class="citation journal cs1">Edgar RS, Green EW, Zhao Y, van Ooijen G, Olmedo M, Qin X, et al. 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Leipzig: Teubner.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Botanische+Forschungen+des+Alexanderzuges&rft.place=Leipzig&rft.pub=Teubner&rft.date=1903&rft.aulast=Bretzl&rft.aufirst=H&rft_id=https%3A%2F%2Farchive.org%2Fdetails%2Fb2486903x&rfr_id=info%3Asid%2Fen.wikipedia.org%3ACircadian+rhythm" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. 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(December 2013)">non-primary source needed</span></a></i>]</sup> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFTurekJoshuKohsakaLin2005" class="citation journal cs1">Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, et al. 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(December 2013)">non-primary source needed</span></a></i>]</sup> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFDelezieDumontDardenteOudart2012" class="citation journal cs1">Delezie J, Dumont S, Dardente H, Oudart H, Gréchez-Cassiau A, Klosen P, et al. 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Cambridge, Massachusetts: Harvard University Press. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-674-13581-9" title="Special:BookSources/978-0-674-13581-9"><bdi>978-0-674-13581-9</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=The+Clocks+that+Time+Us%3A+Physiology+of+the+Circadian+Timing+System&rft.place=Cambridge%2C+Massachusetts&rft.pub=Harvard+University+Press&rft.date=1982&rft.isbn=978-0-674-13581-9&rft.aulast=Moore-Ede&rft.aufirst=MC&rft.au=Sulzman%2C+FM&rft.au=Fuller%2C+CA&rft_id=https%3A%2F%2Farchive.org%2Fdetails%2Fclocksthattimeus0000moor&rfr_id=info%3Asid%2Fen.wikipedia.org%3ACircadian+rhythm" class="Z3988"></span></li></ul> </div> </section><div class="mw-heading mw-heading2 section-heading" onclick="mfTempOpenSection(15)"><span class="indicator mf-icon mf-icon-expand mf-icon--small"></span><h2 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href="https://commons.wikimedia.org/wiki/Category:Circadian_rhythm" class="extiw" title="commons:Category:Circadian rhythm">Circadian rhythm</a></span>.</div></div> </div> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline ul,.mw-parser-output .hlist dl dl,.mw-parser-output .hlist dl ol,.mw-parser-output .hlist dl ul,.mw-parser-output .hlist ol dl,.mw-parser-output .hlist ol ol,.mw-parser-output .hlist ol ul,.mw-parser-output .hlist ul dl,.mw-parser-output .hlist ul ol,.mw-parser-output .hlist ul ul{display:inline}.mw-parser-output .hlist .mw-empty-li{display:none}.mw-parser-output .hlist dt::after{content:": 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Rendering was triggered because: api-parse --> </section></div> <!-- MobileFormatter took 0.056 seconds --><!--esi <esi:include src="/esitest-fa8a495983347898/content" /> --><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?useformat=mobile&type=1x1&usesul3=0" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/w/index.php?title=Circadian_rhythm&oldid=1272694388">https://en.wikipedia.org/w/index.php?title=Circadian_rhythm&oldid=1272694388</a>"</div></div> </div> <div class="post-content" id="page-secondary-actions"> </div> </main> <footer class="mw-footer minerva-footer" role="contentinfo"> <a class="last-modified-bar" href="/w/index.php?title=Circadian_rhythm&action=history"> <div class="post-content last-modified-bar__content"> <span class="minerva-icon minerva-icon-size-medium minerva-icon--modified-history"></span> <span class="last-modified-bar__text modified-enhancement" data-user-name="Three Sixty" data-user-gender="male" data-timestamp="1738186618"> <span>Last edited on 29 January 2025, at 21:36</span> </span> <span class="minerva-icon minerva-icon-size-small minerva-icon--expand"></span> </div> </a> <div class="post-content footer-content"> <div id='mw-data-after-content'> <div class="read-more-container"></div> </div> <div id="p-lang"> <h4>Languages</h4> <section> <ul id="p-variants" class="minerva-languages"></ul> <ul class="minerva-languages"><li class="interlanguage-link interwiki-af mw-list-item"><a href="https://af.wikipedia.org/wiki/Sirkadiese_ritme" title="Sirkadiese ritme – Afrikaans" lang="af" hreflang="af" data-title="Sirkadiese ritme" data-language-autonym="Afrikaans" data-language-local-name="Afrikaans" class="interlanguage-link-target"><span>Afrikaans</span></a></li><li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D9%86%D8%B8%D9%85_%D9%8A%D9%88%D9%85%D8%A7%D9%88%D9%8A" title="نظم يوماوي – Arabic" lang="ar" hreflang="ar" data-title="نظم يوماوي" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-as mw-list-item"><a href="https://as.wikipedia.org/wiki/%E0%A6%9B%E0%A6%A8%E0%A7%8D%E0%A6%A6%E0%A6%83%E0%A6%AA%E0%A7%82%E0%A7%B0%E0%A7%8D%E0%A6%A3_%E0%A6%9A%E0%A6%95%E0%A7%8D%E0%A7%B0" title="ছন্দঃপূৰ্ণ চক্ৰ – Assamese" lang="as" hreflang="as" data-title="ছন্দঃপূৰ্ণ চক্ৰ" data-language-autonym="অসমীয়া" data-language-local-name="Assamese" class="interlanguage-link-target"><span>অসমীয়া</span></a></li><li class="interlanguage-link interwiki-az mw-list-item"><a href="https://az.wikipedia.org/wiki/Sirkad_ritmi" title="Sirkad ritmi – Azerbaijani" lang="az" hreflang="az" data-title="Sirkad ritmi" data-language-autonym="Azərbaycanca" data-language-local-name="Azerbaijani" class="interlanguage-link-target"><span>Azərbaycanca</span></a></li><li class="interlanguage-link interwiki-bn mw-list-item"><a href="https://bn.wikipedia.org/wiki/%E0%A6%A6%E0%A7%87%E0%A6%B9%E0%A6%98%E0%A6%A1%E0%A6%BC%E0%A6%BF" title="দেহঘড়ি – Bangla" lang="bn" hreflang="bn" data-title="দেহঘড়ি" data-language-autonym="বাংলা" data-language-local-name="Bangla" class="interlanguage-link-target"><span>বাংলা</span></a></li><li class="interlanguage-link interwiki-bg mw-list-item"><a href="https://bg.wikipedia.org/wiki/%D0%A6%D0%B8%D1%80%D0%BA%D0%B0%D0%B4%D0%B5%D0%BD_%D1%80%D0%B8%D1%82%D1%8A%D0%BC" title="Циркаден ритъм – Bulgarian" lang="bg" hreflang="bg" data-title="Циркаден ритъм" data-language-autonym="Български" data-language-local-name="Bulgarian" class="interlanguage-link-target"><span>Български</span></a></li><li class="interlanguage-link interwiki-bs mw-list-item"><a href="https://bs.wikipedia.org/wiki/Jednodnevni_biolo%C5%A1ki_ritam" title="Jednodnevni biološki ritam – Bosnian" lang="bs" hreflang="bs" data-title="Jednodnevni biološki ritam" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target"><span>Bosanski</span></a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Ritme_circadiari" title="Ritme circadiari – Catalan" lang="ca" hreflang="ca" data-title="Ritme circadiari" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-cs mw-list-item"><a href="https://cs.wikipedia.org/wiki/Cirkadi%C3%A1nn%C3%AD_rytmus" title="Cirkadiánní rytmus – Czech" lang="cs" hreflang="cs" data-title="Cirkadiánní rytmus" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target"><span>Čeština</span></a></li><li class="interlanguage-link interwiki-cy mw-list-item"><a href="https://cy.wikipedia.org/wiki/Rhythm_circadaidd" title="Rhythm circadaidd – Welsh" lang="cy" hreflang="cy" data-title="Rhythm circadaidd" data-language-autonym="Cymraeg" data-language-local-name="Welsh" class="interlanguage-link-target"><span>Cymraeg</span></a></li><li class="interlanguage-link interwiki-da mw-list-item"><a href="https://da.wikipedia.org/wiki/D%C3%B8gnrytme" title="Døgnrytme – Danish" lang="da" hreflang="da" data-title="Døgnrytme" data-language-autonym="Dansk" data-language-local-name="Danish" class="interlanguage-link-target"><span>Dansk</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Circadiane_Rhythmik" title="Circadiane Rhythmik – German" lang="de" hreflang="de" data-title="Circadiane Rhythmik" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-et mw-list-item"><a href="https://et.wikipedia.org/wiki/Tsirkadiaanr%C3%BCtm" title="Tsirkadiaanrütm – Estonian" lang="et" hreflang="et" data-title="Tsirkadiaanrütm" data-language-autonym="Eesti" data-language-local-name="Estonian" class="interlanguage-link-target"><span>Eesti</span></a></li><li class="interlanguage-link interwiki-el mw-list-item"><a href="https://el.wikipedia.org/wiki/%CE%9A%CE%B9%CF%81%CE%BA%CE%AC%CE%B4%CE%B9%CE%BF%CF%82_%CF%81%CF%85%CE%B8%CE%BC%CF%8C%CF%82" title="Κιρκάδιος ρυθμός – Greek" lang="el" hreflang="el" data-title="Κιρκάδιος ρυθμός" data-language-autonym="Ελληνικά" data-language-local-name="Greek" class="interlanguage-link-target"><span>Ελληνικά</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Ritmo_circadiano" title="Ritmo circadiano – Spanish" lang="es" hreflang="es" data-title="Ritmo circadiano" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-eo mw-list-item"><a href="https://eo.wikipedia.org/wiki/Tagnokta_ritmo" title="Tagnokta ritmo – Esperanto" lang="eo" hreflang="eo" data-title="Tagnokta ritmo" data-language-autonym="Esperanto" data-language-local-name="Esperanto" class="interlanguage-link-target"><span>Esperanto</span></a></li><li class="interlanguage-link interwiki-eu mw-list-item"><a href="https://eu.wikipedia.org/wiki/Erritmo_zirkadiano" title="Erritmo zirkadiano – Basque" lang="eu" hreflang="eu" data-title="Erritmo zirkadiano" data-language-autonym="Euskara" data-language-local-name="Basque" class="interlanguage-link-target"><span>Euskara</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%DA%86%D8%B1%D8%AE%D9%87_%D8%B4%D8%A8%D8%A7%D9%86%D9%87%E2%80%8C%D8%B1%D9%88%D8%B2%DB%8C" title="چرخه شبانهروزی – Persian" lang="fa" hreflang="fa" data-title="چرخه شبانهروزی" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Rythme_circadien" title="Rythme circadien – French" lang="fr" hreflang="fr" data-title="Rythme circadien" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Ritmo_circadiano" title="Ritmo circadiano – Galician" lang="gl" hreflang="gl" data-title="Ritmo circadiano" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target"><span>Galego</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%ED%99%9C%EB%8F%99%EC%9D%BC_%EC%A3%BC%EA%B8%B0" title="활동일 주기 – Korean" lang="ko" hreflang="ko" data-title="활동일 주기" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-hy mw-list-item"><a href="https://hy.wikipedia.org/wiki/%D5%91%D5%AB%D6%80%D5%AF%D5%A1%D5%A4%D5%A1%D5%B5%D5%AB%D5%B6_%D5%BC%D5%AB%D5%A9%D5%B4" title="Ցիրկադային ռիթմ – Armenian" lang="hy" hreflang="hy" data-title="Ցիրկադային ռիթմ" data-language-autonym="Հայերեն" data-language-local-name="Armenian" class="interlanguage-link-target"><span>Հայերեն</span></a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Ritme_sirkadian" title="Ritme sirkadian – Indonesian" lang="id" hreflang="id" data-title="Ritme sirkadian" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target"><span>Bahasa Indonesia</span></a></li><li class="interlanguage-link interwiki-is mw-list-item"><a href="https://is.wikipedia.org/wiki/D%C3%A6gursveifla" title="Dægursveifla – Icelandic" lang="is" hreflang="is" data-title="Dægursveifla" data-language-autonym="Íslenska" data-language-local-name="Icelandic" class="interlanguage-link-target"><span>Íslenska</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Ritmo_circadiano" title="Ritmo circadiano – Italian" lang="it" hreflang="it" data-title="Ritmo circadiano" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%A9%D7%A2%D7%95%D7%9F_%D7%A6%D7%99%D7%A8%D7%A7%D7%93%D7%99" title="שעון צירקדי – Hebrew" lang="he" hreflang="he" data-title="שעון צירקדי" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target"><span>עברית</span></a></li><li class="interlanguage-link interwiki-kk mw-list-item"><a href="https://kk.wikipedia.org/wiki/%D0%A6%D0%B8%D1%80%D0%BA%D0%B0%D0%B4%D0%B0%D0%BB%D1%8B%D2%9B_%D1%80%D0%B8%D1%82%D0%BC" title="Циркадалық ритм – Kazakh" lang="kk" hreflang="kk" data-title="Циркадалық ритм" data-language-autonym="Қазақша" data-language-local-name="Kazakh" class="interlanguage-link-target"><span>Қазақша</span></a></li><li class="interlanguage-link interwiki-ht mw-list-item"><a href="https://ht.wikipedia.org/wiki/Ritm_sikadyen" title="Ritm sikadyen – Haitian Creole" lang="ht" hreflang="ht" data-title="Ritm sikadyen" data-language-autonym="Kreyòl ayisyen" data-language-local-name="Haitian Creole" class="interlanguage-link-target"><span>Kreyòl ayisyen</span></a></li><li class="interlanguage-link interwiki-la mw-list-item"><a href="https://la.wikipedia.org/wiki/Numerus_circadianus" title="Numerus circadianus – Latin" lang="la" hreflang="la" data-title="Numerus circadianus" data-language-autonym="Latina" data-language-local-name="Latin" class="interlanguage-link-target"><span>Latina</span></a></li><li class="interlanguage-link interwiki-hu mw-list-item"><a href="https://hu.wikipedia.org/wiki/Cirkadi%C3%A1n_ritmus" title="Cirkadián ritmus – Hungarian" lang="hu" hreflang="hu" data-title="Cirkadián ritmus" data-language-autonym="Magyar" data-language-local-name="Hungarian" class="interlanguage-link-target"><span>Magyar</span></a></li><li class="interlanguage-link interwiki-ml mw-list-item"><a href="https://ml.wikipedia.org/wiki/%E0%B4%85%E0%B4%A8%E0%B5%8D%E0%B4%A4%E0%B5%BC%E0%B4%9C%E0%B4%BE%E0%B4%A4-%E0%B4%A8%E0%B4%BF%E0%B4%9C%E0%B4%BE%E0%B4%B5%E0%B5%BC%E0%B4%A4%E0%B5%8D%E0%B4%A4%E0%B4%A8%E0%B4%82" title="അന്തർജാത-നിജാവർത്തനം – Malayalam" lang="ml" hreflang="ml" data-title="അന്തർജാത-നിജാവർത്തനം" data-language-autonym="മലയാളം" data-language-local-name="Malayalam" class="interlanguage-link-target"><span>മലയാളം</span></a></li><li class="interlanguage-link interwiki-ms mw-list-item"><a href="https://ms.wikipedia.org/wiki/Ritma_sirkadian" title="Ritma sirkadian – Malay" lang="ms" hreflang="ms" data-title="Ritma sirkadian" data-language-autonym="Bahasa Melayu" data-language-local-name="Malay" class="interlanguage-link-target"><span>Bahasa Melayu</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Circadiaan_ritme" title="Circadiaan ritme – Dutch" lang="nl" hreflang="nl" data-title="Circadiaan ritme" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E6%A6%82%E6%97%A5%E3%83%AA%E3%82%BA%E3%83%A0" title="概日リズム – Japanese" lang="ja" hreflang="ja" data-title="概日リズム" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-no mw-list-item"><a href="https://no.wikipedia.org/wiki/D%C3%B8gnrytme" title="Døgnrytme – Norwegian Bokmål" lang="nb" hreflang="nb" data-title="Døgnrytme" data-language-autonym="Norsk bokmål" data-language-local-name="Norwegian Bokmål" class="interlanguage-link-target"><span>Norsk bokmål</span></a></li><li class="interlanguage-link interwiki-nn mw-list-item"><a href="https://nn.wikipedia.org/wiki/D%C3%B8gnrytme" title="Døgnrytme – Norwegian Nynorsk" lang="nn" hreflang="nn" data-title="Døgnrytme" data-language-autonym="Norsk nynorsk" data-language-local-name="Norwegian Nynorsk" class="interlanguage-link-target"><span>Norsk nynorsk</span></a></li><li class="interlanguage-link interwiki-oc mw-list-item"><a href="https://oc.wikipedia.org/wiki/Ritme_circadian" title="Ritme circadian – Occitan" lang="oc" hreflang="oc" data-title="Ritme circadian" data-language-autonym="Occitan" data-language-local-name="Occitan" class="interlanguage-link-target"><span>Occitan</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Rytm_dobowy" title="Rytm dobowy – Polish" lang="pl" hreflang="pl" data-title="Rytm dobowy" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Ritmo_circadiano" title="Ritmo circadiano – Portuguese" lang="pt" hreflang="pt" data-title="Ritmo circadiano" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ro mw-list-item"><a href="https://ro.wikipedia.org/wiki/Ritm_circadian" title="Ritm circadian – Romanian" lang="ro" hreflang="ro" data-title="Ritm circadian" data-language-autonym="Română" data-language-local-name="Romanian" class="interlanguage-link-target"><span>Română</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%A6%D0%B8%D1%80%D0%BA%D0%B0%D0%B4%D0%BD%D1%8B%D0%B9_%D1%80%D0%B8%D1%82%D0%BC" title="Циркадный ритм – Russian" lang="ru" hreflang="ru" data-title="Циркадный ритм" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-si mw-list-item"><a href="https://si.wikipedia.org/wiki/%E0%B6%AF%E0%B7%9B%E0%B6%B1%E0%B7%92%E0%B6%9A_%E0%B6%BB%E0%B7%92%E0%B6%AF%E0%B7%8A%E0%B6%B8%E0%B6%BA" title="දෛනික රිද්මය – Sinhala" lang="si" hreflang="si" data-title="දෛනික රිද්මය" data-language-autonym="සිංහල" data-language-local-name="Sinhala" class="interlanguage-link-target"><span>සිංහල</span></a></li><li class="interlanguage-link interwiki-simple mw-list-item"><a href="https://simple.wikipedia.org/wiki/Circadian_rhythm" title="Circadian rhythm – Simple English" lang="en-simple" hreflang="en-simple" data-title="Circadian rhythm" data-language-autonym="Simple English" data-language-local-name="Simple English" class="interlanguage-link-target"><span>Simple English</span></a></li><li class="interlanguage-link interwiki-sl mw-list-item"><a href="https://sl.wikipedia.org/wiki/Cirkadiani_ritem" title="Cirkadiani ritem – Slovenian" lang="sl" hreflang="sl" data-title="Cirkadiani ritem" data-language-autonym="Slovenščina" data-language-local-name="Slovenian" class="interlanguage-link-target"><span>Slovenščina</span></a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/%D0%A6%D0%B8%D1%80%D0%BA%D0%B0%D0%B4%D0%B8%D1%98%D0%B0%D0%BB%D0%BD%D0%B8_%D1%80%D0%B8%D1%82%D0%B0%D0%BC" title="Циркадијални ритам – Serbian" lang="sr" hreflang="sr" data-title="Циркадијални ритам" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target"><span>Српски / srpski</span></a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Cirkadijani_ritam" title="Cirkadijani ritam – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Cirkadijani ritam" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target"><span>Srpskohrvatski / српскохрватски</span></a></li><li class="interlanguage-link interwiki-fi mw-list-item"><a href="https://fi.wikipedia.org/wiki/Sis%C3%A4inen_kello" title="Sisäinen kello – Finnish" lang="fi" hreflang="fi" data-title="Sisäinen kello" data-language-autonym="Suomi" data-language-local-name="Finnish" class="interlanguage-link-target"><span>Suomi</span></a></li><li class="interlanguage-link interwiki-sv badge-Q17437798 badge-goodarticle mw-list-item" title="good article badge"><a href="https://sv.wikipedia.org/wiki/Dygnsrytm" title="Dygnsrytm – Swedish" lang="sv" hreflang="sv" data-title="Dygnsrytm" data-language-autonym="Svenska" data-language-local-name="Swedish" class="interlanguage-link-target"><span>Svenska</span></a></li><li class="interlanguage-link interwiki-tr mw-list-item"><a href="https://tr.wikipedia.org/wiki/Biyolojik_saat" title="Biyolojik saat – Turkish" lang="tr" hreflang="tr" data-title="Biyolojik saat" data-language-autonym="Türkçe" data-language-local-name="Turkish" class="interlanguage-link-target"><span>Türkçe</span></a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/%D0%A6%D0%B8%D1%80%D0%BA%D0%B0%D0%B4%D0%BD%D0%B8%D0%B9_%D1%80%D0%B8%D1%82%D0%BC" title="Циркадний ритм – Ukrainian" lang="uk" hreflang="uk" data-title="Циркадний ритм" data-language-autonym="Українська" data-language-local-name="Ukrainian" class="interlanguage-link-target"><span>Українська</span></a></li><li class="interlanguage-link interwiki-ur mw-list-item"><a href="https://ur.wikipedia.org/wiki/%DB%8C%D9%88%D9%85%DB%8C%DB%81_%D8%AA%D8%A8%D8%AF%DB%8C%D9%84%DB%8C" title="یومیہ تبدیلی – Urdu" lang="ur" hreflang="ur" data-title="یومیہ تبدیلی" data-language-autonym="اردو" data-language-local-name="Urdu" class="interlanguage-link-target"><span>اردو</span></a></li><li class="interlanguage-link interwiki-vi mw-list-item"><a href="https://vi.wikipedia.org/wiki/Nh%E1%BB%8Bp_%C4%91i%E1%BB%87u_sinh_h%E1%BB%8Dc_h%E1%BA%B1ng_ng%C3%A0y" title="Nhịp điệu sinh học hằng ngày – Vietnamese" lang="vi" hreflang="vi" data-title="Nhịp điệu sinh học hằng ngày" data-language-autonym="Tiếng Việt" data-language-local-name="Vietnamese" class="interlanguage-link-target"><span>Tiếng Việt</span></a></li><li class="interlanguage-link interwiki-zh-yue mw-list-item"><a href="https://zh-yue.wikipedia.org/wiki/%E6%99%9D%E5%A4%9C%E7%AF%80%E5%BE%8B" title="晝夜節律 – Cantonese" lang="yue" hreflang="yue" data-title="晝夜節律" data-language-autonym="粵語" data-language-local-name="Cantonese" class="interlanguage-link-target"><span>粵語</span></a></li><li class="interlanguage-link interwiki-zh mw-list-item"><a href="https://zh.wikipedia.org/wiki/%E6%98%BC%E5%A4%9C%E8%8A%82%E5%BE%8B" title="昼夜节律 – Chinese" lang="zh" hreflang="zh" data-title="昼夜节律" data-language-autonym="中文" data-language-local-name="Chinese" class="interlanguage-link-target"><span>中文</span></a></li></ul> </section> </div> <div class="minerva-footer-logo"><img src="/static/images/mobile/copyright/wikipedia-wordmark-en.svg" alt="Wikipedia" width="120" height="18" style="width: 7.5em; height: 1.125em;"/> </div> <ul id="footer-info" class="footer-info hlist hlist-separated"> <li id="footer-info-lastmod"> This page was last edited on 29 January 2025, at 21:36<span class="anonymous-show"> (UTC)</span>.</li> <li id="footer-info-copyright">Content is available under <a class="external" rel="nofollow" href="https://creativecommons.org/licenses/by-sa/4.0/deed.en">CC BY-SA 4.0</a> unless otherwise noted.</li> </ul> <ul id="footer-places" class="footer-places hlist hlist-separated"> <li id="footer-places-privacy"><a 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