Circadian Rhythm | Gentle Sleep Reading

0:00You're listening to a Glassbox Media podcast. This is your fix. I am your host, Stasi Schroeder. Welcome to Tell Me Lies, the official podcast. What's the most unhinged thing of these in three? Steven, because he's so evil. I do think he is misunderstood. You see everyone base consequences. It's intoxicating. The writers just know how to trick you. There's always a twist in this show. Tell me Lies, the official podcast January 6th, and stream the new season of Tell Me Lies January 13th on Hulu and Hulu on Disney+. Let's talk about those nights when sleep feels impossible to catch. I know that feeling all too well. And if you're anything like me, sometimes you need a bit more than just winding down. That's where something like sleep magic and really make a difference. Jessica Porter, the host of sleep magic,

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2:00It's free and easy to find. Just search Sleep Magic on your favorite podcast app and see where it takes you. Welcome to the I Can't Sleep Podcast where I help you drift off one fact at a time. I'm your host, Benjamin Boster. And today's episode is about circadian rhythm. Spring starts at the Home Depot and we are bringing the heat to your backyard this season. Fire up the flavor with our wide variety of grills for under $300. Like the next grill for burner gas grill that's perfect for hosting your spring cookout. Then set the scene and turn your outdoor space into the go-to spot the patio sets for every budget. Bring it this season with grills that deliver flavor and patios that set the vibe from the Home Depot. Start your spring with low prices guaranteed at the Home Depot. ExclusionSupplySeaHome Depot.com slash price match for details. This is Andrew Huberman, host of the Huberman Lab Podcast. I'm excited to share that the performance I wear company Roca and I

3:01have teamed up to create a pair of red lens glasses. These are meant to be worn in the evening after the sun goes down. They filter out short wavelength light that comes from screens and from LED lights, which are the two most common indoor lights nowadays. I want to emphasize that these are not traditional blue blockers. Yes, they filter out blue light, but they also filter out all the other wavelengths of light that can suppress your melatonin and other hormones, which can degrade your sleep. By wearing these glasses in the evening, I find it much easier to wind down at night and it makes the transition into sleep greatly improved. If you would like to try these red lens wind-down glasses, simply go to roca.com. That's roca.com and enter the code Huberman to save 20% off your first order. Again, that's roca.com and enter the code Huberman at checkout. A circadian rhythm or circadian cycle is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates

4:04within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock, whose primary function is to rhythmically coordinate biological processes, so they occur at the correct time to maximize the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi, and cyanobacteria, and there is evidence that they evolved independently in each of these kingdoms of life. The term circadian comes from the Latin Circa, meaning around, and Dia's, meaning days. Processes with 24-hour cycles are more generally called diurnal rhythms.

5:07Diurnal rhythms should not be called circadian rhythms, unless they can be confirmed as endogenous and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues, called zeitgebers, from German zeitgeber, literally meaning time giver, which include light, temperature, and redox cycles. In clinical settings, an abnormal circadian rhythm in humans is known as a circadian rhythm sleep disorder. The earliest recorded account of a circadian process is credited to the Cyaphrastis, dating from the 4th century BC, probably provided to him by a report of Androsthenes, a ship's captain serving under Alexander the Great.

6:12In his book, Perry Futon Historia, or Encore into Plans, the Cyaphrastis describes a tree with many leaves like the rose, and that this closes at night, but opens its 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. The mentioned tree was much later identified as a tamarind tree by the botanist H. Pretzel in his book on the botanical findings of the Alexandrian campaigns. The observation of a circadian or diurnal process in humans is mentioned in Chinese medical texts dated to around the 13th century, including the noon and midnight manual and the mnemonic rhyme

7:15to aid in the selection of acupoints according to the diurnal cycle the day of the month and the season of the year. In 1729, French scientist Jean-Jacques d'Orthouse d'Amarin 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 may mosa poudica persisted, even when the plants were capped in constant darkness. In 1896, Patrick and Gilbert observed that during a prolonged period of sleep deprivation, sleepiness increases and decreases with a period of approximately 24 hours. In 1918, JS Semansky showed that animals are capable

8:21of maintaining 24-hour activity patterns in the absence of external cues, such as light and changes in temperature. In the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. August 4-L, Engaborgabelling, and Oscarval conducted numerous experiments to determine whether this rhythm was attributed to an endogenous clock. The existence of circadian rhythm was independently discovered in fruit flies in 1935 by two German zoologists, Hans Kalmus, and Irving Birnig. In 1954, an important experiment reported by Colin Pettendry demonstrated that occlusion, the process of pupa turning

9:22into adult and drosophila sudo obscura, was a circadian behavior. He demonstrated that while temperature played a vital role in occlusion rhythm, the period of occlusion was delayed but not stopped when temperature was decreased. The term circadian was coined by Franz Halberg in 1959. According to Halberg's original definition, the term circadian was derived from circa about and dias 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,

10:22by a few minutes or hours. In 1977, the International Committee on Nomenclature of the International Society of Chronobiology formally adopted the definition circadian, relating to biologic variations or rhythms, with a frequency of one cycle and 24 plus or minus four hours. circa about approximately and dias day or 24 hour. Note, term describes rhythms within about 24-hour cycle length, whether they are frequency synchronized with or are desynchronized or free running from the local environmental timescale, with periods of slightly yet consistently different from 24 hour. Ron Kanapka and Seymour Benzer identified the first clock mutation

11:25in Drosophila in 1971, naming the gene period gene. The first discovered genetic determinant of behavioral rhythmicity. The period gene was isolated in 1984 by two teams of researchers. Kanapka, Jeffrey Hall, Michael Rochbash and their team showed that the period locus is the center of the circadian rhythm, and that the loss of periods stops circadian activity. At the same time, Michael W. Young's team reported similar effects of period, and that the gene covers 7.1 kilobase interval on the X chromosome and encodes of 4.5 kilobase poly A plus RNA. They went on to discover the key genes and neurons in Drosophila circadian system,

12:27from which Hall, Rochbash and Young received the Nobel Prize in Physiology or Medicine 2017. Joseph Takahashi discovered the first mammalian circadian clock mutation using mice in 1994. However, recent studies show that deletion of clock does not lead to a behavioral phenotype. The animals still have normal circadian rhythms, which questions its importance in rhythm generation. The first human clock mutation was identified in an extended Utah family by Chris Jones, and genetically characterized by Ying Hu Fu and Luis Atachik. Effected individuals are extreme morning larks, with four-hour advanced sleep and other rhythms.

13:28This form of familial advanced sleep phase syndrome is caused by a single amino acid change and S662 to G mutation in the human per to protein. To be called circadian, a biological rhythm must meet these three general criteria. One, the rhythm has an endogenously derived free running period of time that lasts approximately 24 hours. The rhythm persists in constant conditions, i.e. constant darkness, was 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 Tau. The rationale for this criterion is to distinguish circadian rhythms from simple responses to daily external cues.

14:37A rhythm cannot be said to be endogenous unless it has been tested and persists in conditions without external periodic input. Indyurnal animals active during daylight hours, in general Tau is slightly greater than 24 hours, whereas in nocturnal animals active at night, in general Tau is shorter than 24 hours. Two, the rhythms are untrainable. The rhythm can be reset by exposure to external stimuli such as light and heat, a process called entrainment. The external stimulus used to entrain a rhythm is called desiccabur or time giver. Travel across time zones illustrates the ability of the human biological clock to adjust to the local time.

15:38A person will usually experience jet lag before entrainment of their circadian clock has brought it into sync with local time. Three, the rhythms exhibit temperature compensation. 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 kinetics of all molecular processes in their cells. In order to keep track of time, the organism circadian clock must maintain roughly a 24 hour periodicity despite the changing kinetics, a property known as temperature compensation. The Q10 temperature coefficient is a measure of this compensating effect.

16:43If the Q10 coefficient remains approximately 1 as temperature increases, the rhythm is considered to be temperature compensated. 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 internal metabolic processes as in coordinating with the environment.

17:46This is suggested by the maintenance, heritability of circadian rhythms and fruit flies after several hundred generations in constant laboratory conditions, as well as in creatures in constant darkness in the wild, and by the experimental elimination of behavioral, but not physiological, circadian rhythms in coil. What drove circadian rhythms to evolve has been an enigmatic question. Previous hypotheses emphasize that photosensitive proteins and circadian rhythms may have originated together in the earliest cells, with a purpose of protecting replicating DNA from high levels of damaging ultraviolet radiation during the daytime. As a result, replication was relegated to the dark.

18:49However, 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. Recent studies instead highlight the importance of co-evolution of redox proteins with circadian oscillators in all three domains of life, following the great oxidation event approximately 2.3 billion years ago. The current view is that circadian changes in environmental oxygen levels and the production of reactive oxygen species or OS in the presence of daylight are likely to have driven a need to evolve circadian rhythms to preempt and therefore counteract damaging redox reactions on a daily basis.

19:53The simplest known circadian clocks are bacterial circadian rhythms exemplified by the prokaryote cyanobacteria. Recent research has demonstrated that the circadian clock of synagogues along it is can be reconstituted in vitro, with just the three proteins of their central oscillator. This clock has been shown to sustain a 22 hour rhythm over several days upon the addition of ATP. Previous explanations of the prokaryotic circadian timekeeper were dependent upon a DNA transcription translation feedback mechanism. A defect in the human homologue of the Drosophila period gene was identified as a cause of the sleep disorder FASPS, familial advanced sleep phase syndrome, underscoring the conserved nature of the molecular circadian clock through evolution.

21:08Many 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 at the cells of the body interpret as a specific time of the day. It is now known that the molecular circadian clock can function within a single cell, that is, it is cell autonomous. This was shown by gene block in isolated mollusk basal retinal neurons BRNs. At the same time different cells may communicate with each other, resulting in a synchronized output of electrical signaling. These may interface with endocrine glands of the brain to result in periodic release of hormones.

22:12The 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 is relayed by the eyes travel 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, or coordinatedly controlled by the biological clock. Circadian rismicity is present in the sleeping and feeding patterns of animals, including human beings. There are also clear patterns of core body temperature, brain wave activity, hormone production, cell regeneration, and other biological activities.

23:14In addition, photoperiodism, the physiological reaction of organisms to the length of day or night, is vital to both plants and animals. And this circadian system plays a role in the measurement and interpretation of day lengths. Timely predictions of seasonal periods of weather conditions, food availability, or predator activity is crucial for survival of many species. Although not the only parameter, a changing length of the photoperiod, day length, is the most predictive environmental cue for this seasonal timing of physiology and behavior, most notably for timing of migration, hibernation, and reproduction. Mutations or deletions of clock genes in mice have demonstrated the importance of body clocks to ensure the proper timing of cellular metabolic events.

24:26Clock mutant mice are hyperphagic and obese, and have older glucose metabolism. In mice, deletion of the Rev-Urb-A-Alpha-Clock gene can result in diet-induced obesity, and changes the balance between glucose and lipid utilization, predisposing to diabetes. However, it is not clear whether there is a strong association between clock gene polymorphisms and humans, and the susceptibility to develop the metabolic syndrome. The rhythm is linked to the light-dark cycle. Animals, including humans, kept in total darkness for extended periods eventually function was a free-running rhythm. Their sleep cycle is pushed back or forward each day, depending on whether their day, their endogenous period, is shorter or longer than 24 hours.

25:31The environmental cues that reset the rhythms each day are called zeitgoopers. Totally blind subterranean mammals are able to maintain their endogenous clock in the apparent absence of external stimuli. Although they lack image-forming eyes, their photoreceptors, which detect light, are still functional. They do surface periodically as well. 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 ultradian rhythms, such as metabolic, hormonal, CNS, electrical, or neurotransmitter rhythms.

26:39Recent research has influenced the design of spacecraft environments, as systems that mimics a light-dark cycle have been found to be highly beneficial to astronauts. Light therapy has been trialled as a treatment for sleep disorders. Norwegian researchers at the University of Tromså have shown that some arctic animals show circadian rhythms, only in the parts of a year that have daily sunrises and sunsets. In one study of reindeer, animals at 70 degrees north showed circadian rhythms in the autumn, winter, and spring, but not in the summer. Reindeer at Svalbard at 78 degrees north 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.

27:49A 2006 study in Northern Alaska found that day-living ground squirrels and nocturnal porcupines strictly maintain their circadian rhythms through 82 days and nights of sunshine. The researchers speculate that these two rodents noticed 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. The navigation of the fall migration of the eastern North American monarch butterfly to their over-wintering grounds in central Mexico uses a time-compensated sun compass that depends upon a circadian clock in their antenna. Circadian rhythm is also known to control mating behaviors in certain moth species, where females produce a specific pheromone that attracts and resets the male circadian rhythm to induce mating at night.

29:03Although light is the primary synchronizer of the circadian rhythm through the supra chiasmatic nucleus, other environmental signals also influence the biological clock. Feeding plays a key role in regulating peripheral clocks found in the liver, muscles, and adipose tissues. Time restricted feeding can adjust these clocks by modifying light signals. Additionally, physical activity affects the circadian phase, notably by adjusting melatonin production and body temperature. Temperature itself is an important synchronizer capable of modifying cellular circadian rhythms. Finally, stress and the release of glucocorticoids influence the expression of clock genes, potentially disrupting biological cycles.

30:06Integrating these factors is essential for understanding circadian rhythms beyond simple light regulation. Plant circadian rhythms tell the plant what season it is and when to flower for the best chance of attracting pollinators. Behaviours showing rhythms include leaf movement, growth, germination, stomatol, gas exchange, enzyme activity, photosynthetic activity, and fragrance emission among others. Circadian rhythms occur as a plant and trains to synchronize with the light cycle of its surrounding environment. These rhythms are endogenously generated, self-sustaining, and are relatively constant over a range of ambient temperatures. Important features include two interacting transcription translation feedback loops.

31:11Proteins containing PIS domains, which facilitate protein to protein interactions, and several photo receptors 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. A better understanding of plants circadian rhythms has applications in agriculture, such as helping farmers stagger crop harvest, to extend crop availability, and securing against massive losses due to weather. Light is the signal by which plants synchronize their internal clocks to their environment and is sensed by a wide variety of photo receptors. Red and blue light are absorbs through several phytochroms and cryptochroms.

32:16Phytochrom A, phi A, is light-layed bile and allows germination and deedialation when light is scarce. Phytochroms B, through E, are more stable with phi B, the main phytochrome and seedlings grown in the light. The cryptochrome gene is also a light-sensitive component of the circadian clock and is sought to be involved both as a photo receptor and as part of the clock's endogenous space maker mechanism. Cryptochroms 1 through 2, involved in blue UVA, help to maintain the period length in the clock through a whole range of light conditions. The central oscillator generates a self-sustaining rhythm and is driven by two interacting feedback loops that are active at different times of day.

33:18The morning loop consists of CCA1 and L-H-Y, which encode closely related NYB transcription factors that regulate circadian rhythms in arabidopsis, as well as PRR7 and 9. The evening loop consists of GI and ELF4, both involved in regulation of flowering time genes. When CCA1 and L-H-Y are overexpressed, plants become erasmic and mRNA signals reduce, contributing to a negative feedback loop. Gene expression of CCA1 and L-H-Y oscillates in peaks in the early morning, whereas TOC1 gene expression oscillates in peaks in the early evening.

34:21While it was previously hypothesized that these three genes model a negative feedback loop in which overexpressed CCA1 and L-H-Y repressed TOC1 and overexpressed TOC1 is a positive regulator of CCA1 and L-H-Y. It was shown in 2012 by Andrew Miller and others that TOC1 in fact serves as a repressor not only of CCA1, L-H-Y 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 TOC1 gene functions and interactions suggests a reframing of the plant circadian clock as a triple negative component repressor later model rather than the positive negative element feedback loop characterized in the clock and mammals.

35:27In 2018, researchers found that the expression of PRR5 and TOC1, H-N-RNA, nascent transcripts, follows the same oscillatory pattern as processed M-RNA transcripts, rhythmically in A-Saleana. L-N-K's binds to the 5 region of PRR5 and TOC1 and interacts with R-NAP2 and other transcription factors. Moreover, R-V-E8-L-N-K's interaction enables the permissive histone mesolation pattern to be modified and the histone modification itself parallels the oscillation of clock gene expression. It has previously been found that matching a plant circadian rhythm to its external environments, light and dark cycles, has the potential to positively affect the plant.

36:32One of these varieties had a normal 24-hour circadian cycle. 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. The arabidopsis with the 24-hour circadian cycle was grown in three different environments. One of these environments had a 20-hour light and dark cycle, the other had a 24-hour light and dark cycle, and the final environment had a 24-hour light and dark cycle. The two mutated plants were grown in both an environment that had a 20-hour light and dark cycle, and an environment that had a 28-hour light and dark cycle. According to the metabolic dawn hypothesis, sugars produced by photosynthesis have potential to help regulate the circadian rhythm and certain photosynthetic and metabolic pathways.

37:37As the sun rises, more light becomes available, which normally allows more photosynthesis to occur. The sugars produced by photosynthesis repress PRR7. This repression of PRR7 then leads to the increased expression of CCA1. On the other hand, decreased photosynthetic sugar levels increase PRR7 expression and decrease CCA1 expression. This feedback loop between CCA1 and PRR7 is what is proposed to cause metabolic dawn.