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Circadian Biological Clock

Sun and Moon, Nuremberg Chronicle, 1493

Source: Albrecht Durer – This is the scan of historical document, Nuremberg chronicle, from the original book, Nuremberg chronicle, Hartmann Schedel, 1493. This work is in the public domain in its country of origin and other countries and areas where the copyright term is the author’s life plus 100 years or less


A circadian clock, or circadian oscillator, is a hypothetical biochemical oscillator that oscillates with a stable phase relationship to 1) ___ time. Such a clock’s in vivo period, averaged over an earth year, is necessarily almost exactly 24 hours (the earth’s current solar day). In most living things, internally synchronized circadian clocks make it possible for the organism to coordinate its biology and behavior with daily environmental changes corresponding with the day-2) ___ cycle and derived diurnal behavior patterns (e.g. crepuscular feeding).


The term circadian derives from the Latin circa (about) diem (a 3) ___), since when taken away from external cues (such as the day-night cycle), they do not run to exactly 24 hours. Clocks in humans in a lab in constant low light, for example, will average about 24.2 hours per day, rather than 24 hours exactly. The normal body clock oscillates with an endogenous period of exactly 24 hours, it entrains, when it receives sufficient daily corrective signals from the environment, primarily daylight and darkness. Circadian clocks are the central mechanisms that drive 4) ___ rhythms. They consist of three major components:


1. a central biochemical oscillator with a period of about 5) ___ hours that keeps time;

2. a series of input pathways to this central oscillator to allow entrainment of the clock;

3. a series of output pathways tied to distinct phases of the oscillator that regulate overt rhythms in biochemistry, physiology, and behavior throughout an organism.


The clock is reset as an organism senses environmental time cues of which the primary one is 6) ___. Circadian oscillators are ubiquitous in tissues of the body where they are synchronized by both endogenous and external signals to regulate transcriptional activity throughout the day in a tissue-specific manner. The circadian 7) ___ is intertwined with most cellular metabolic processes and it is affected by the aging of an organism. The basic molecular mechanisms of the biological clock have been defined in vertebrate species, Drosophila melanogaster, plants, fungi, bacteria, and presumably also in Archaea.


While a precise 24-hour circadian clock is found in many organisms, it is not universal. Organisms living in the high Arctic or high Antarctic do not experience solar time in all seasons, though most are believed to maintain a circadian rhythm close to 24 hours, such as bears during hibernation. Much of the earth’s biomass resides in the dark biosphere, and while these organisms may exhibit rhythmic physiology, for these organisms the dominant rhythm is unlikely to be circadian. For east-west migratory organisms – and especially should an organism circumnavigate the globe – the absolute 24-hour phase might deviate over months, seasons, or years.


In vertebrates, the master circadian clock is contained within the suprachiasmatic nucleus (SCN), a bilateral nerve cluster of about 20,000 neurons. The SCN itself is located in the hypothalamus, a small region of the 8) ___ situated directly above the optic chiasm, where it receives input from specialized photosensitive ganglion cells in the retina via the retinohypothalamic tract. The SCN maintains control across the body by synchronizing “slave oscillators“, which exhibit their own near-24-hour rhythms and control circadian phenomena in local tissue. Through intercellular signaling mechanisms such as vasoactive intestinal peptide, the SCN signals other hypothalamic nuclei and the pineal gland to modulate body temperature and production of hormones such as cortisol and melatonin; these 9) ___ enter the circulatory system, and induce clock-driven effects throughout the organism. It is not, however, clear precisely what signal (or signals) enacts principal entrainment to the many biochemical clocks contained in tissues throughout the body.


A key feature of clocks is their ability to synchronize to external stimuli. The presence of cell autonomous oscillators in almost every cell in the 10) ____ raises the question of how these oscillators are temporally coordinated. The quest for universal timing cues for peripheral clocks in mammals has yielded principal entrainment signals such as feeding, temperature, and oxygen. Both feeding rhythms and temperature cycles were shown to synchronize peripheral clocks and even uncouple them from the master clock in the brain (e.g., daytime restricted feeding). Recently, oxygen rhythms were found to synchronize clocks in cultured cells.

Sources: nih.gov; Wikipedia


ANSWERS: 1) solar; 2) night; 3) day; 4) circadian; 5) 24; 6) light; 7) clock; 8) brain; 9) hormones; 10) body


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