24-Hour Service: The Circadian Clock

Have you ever woken up minutes before your alarm sounded?  This strange phenomenon isn’t just a bizarre coincidence!  Like most living things, we have an extremely accurate and powerful internal biological clock.  As its name implies, this circadian clock operates over “about a day” and is responsible for controlling our sleep-wake cycles, digestive activities, mood, and many other physiological processes.  In order to achieve such global results, the circadian rhythm operates over a hierarchy of oscillators that function at the cellular, tissue, and systems levels.

Woman holding alarm clock

At the top of the hierarchy are the suprachiasmatic nuclei (SCN), which receive information about light and dark from the retina.  The SCN entrain the circadian system to the environmental light/dark cycles and synchronize the clocks in various organs and tissues.  Through electrical, endocrine, and metabolic signaling pathways, the SCN helps orchestrate the onset of certain behaviors and tissue activities.  For example, when you fall asleep, breathing slows, body temperature lowers, muscles relax, and the hormone melatonin is released.

The SCN has long since been identified as a dominant circadian pacemaker.  Recently, the discovery of “clock genes” has revealed that the capacity for circadian pacemaker activity is widespread throughout the body.  Indeed, most peripheral organs, like the liver and kidneys, express circadian oscillations in isolation of the SCN!  This may explain why you feel hungry at around the same time every day, no matter how sunny or gloomy the day has been.

SCN as central chronographer

Disturbances in the communication between the many body clocks can desynchronize circadian systems and is believed to contribute to the development of diseases like obesity and neuropsychiatric disorders.  For example, rotating shift-work and sleep deprivation are known to dampen rhythms in growth hormone and melatonin, raise stress hormone cortisol levels, and cause weight gain.  Studies in mice have validated the link between a functional circadian system and metabolic homeostasis.  Mice with a mutation in a gene named Clock have slower metabolism, impaired glucose tolerance, reduced insulin secretion, and obesity.  Thus, perturbations of the circadian system lead to de-synchronization of many body clocks.

In humans, mood disorders often go hand-in-hand with metabolic disorders, eating disorders, and obesity.  Chronic shift-work is hypothesized to cause mood disorders, possibly due to a misalignment of rhythms in body temperature, melatonin, and sleep.  Conversely, individuals that suffer from mood disorders benefit from strict daily routines, including strict bedtime and mealtimes.  These routines probably help synchronize the various biological clocks to maintain the integrity of the circadian system and physiology.

A recently recognized mood disorder related to the misalignment between external cues and internal rhythms is seasonal affective disorder (SAD).  This type of depression usually occurs in the winter and can often be treated with light therapy.  While the mechanism of this treatment is unknown, it is possible that light, which suppresses melatonin secretion by the pineal gland, may entrain the circadian system, resetting the clock phase in the SCN.  To help keep your circadian system in check, make sure you get enough sunlight this winter!

For those of you who travel across the country or internationally this holiday season, you may want to consider how to avoid becoming jet lagged.  Since we are not evolved to adjust to abrupt time changes, you need to give yourself about a day to shift one time zone.  Otherwise, you will be sleepy in the middle of the afternoon or wide-awake in the middle of the night!  Since light is such a powerful stimulus, try to control when you are exposed to light during the flight.  Also, after you arrive and are getting ready for bed, don’t eat a large meal because your body is not prepared to metabolize food at that time.  Lastly, create as dim an environment as possible so your internal clocks can be reset.  Hopefully, these tips will help alleviate your jet lag!


Images adapted from Tetra Images/Corbis, Malenkov in Exile/Flickr, and 55Laney69/Flickr.

Kate Fehlhaber

Kate graduated from Scripps College in 2009 with a Bachelor of Arts degree in Neuroscience, completing the cellular and molecular track with honors. As an undergraduate, she studied long-term plasticity in models of Parkinson’s disease in a neurobiology lab at University of California, Los Angeles. She continued this research as lab manager before entering the University of Southern California Neuroscience graduate program in 2011 and then transferring to UCLA in 2013. She completed her PhD in 2017, where her research focused on understanding the communication between neurons in the eye. Kate founded Knowing Neurons in 2011, and her passion for creative science communication has continued to grow.