What Is the Circadian Timing System? An Introduction to Chronobiology

August 5, 2019

Life has evolved to thrive in Earth’s specific environmental characteristics, of which the cycle of sunlight and nighttime is particularly pervasive. So, naturally, all living organisms are heavily influenced by this cycle. Humans are no exception.

The most obvious example of the influence of the dark-light cycle in our life is sleep. But there are many other behaviors and biological functions that follow a similar rhythm, such as food intake, metabolism and blood pressure, for example.

In fact, most, if not all, bodily functions have some degree of day-night rhythmicity. These 24-hour cycles in biology and behavior are called circadian rhythms (from the Latin “circa”=about, and “dies”=day).

In this article, we will learn about the physiological system that generates and synchronizes circadian rhythms with our environmental light–dark cycle: the circadian timing system.

What Is The Circadian Timing System?

The circadian timing system is our body’s intrinsic timekeeping mechanism. It’s what we usually call the biological clock: the clock that controls the rhythms of time-dependent biological processes. The science that studies these processes is called chronobiology.

Just as we have diurnal (wakefulness, activity, feeding) and nocturnal (sleep, rest, fasting) behaviors, so do the cells and systems in our body have a “biological day” and a “biological night.”

The circadian timing system is the biological pacemaker that regulates endocrine and metabolic rhythms to establish a coherent pattern of cellular activity. The biological clock coordinates interdependent pathways and functions, separates in time incompatible pathways and functions, and synchronizes our biology and behavior with the environment.

During the biological day, to promote wakefulness and support physical activity and feeding, the circadian timing system shifts metabolism to a state of energy production and energy storage. It does so by favoring hormonal signals (e.g., increased insulin signaling, decreased leptin) and metabolic pathways that promote the use of nutrients (glucose, fatty acids) to produce cell energy (in the form of ATP) and to replenish energy reserves (glycogen, triglycerides).

Conversely, during the biological night, the circadian timing system promotes sleep and shifts metabolism to a state of mobilization of stored energy by favoring hormonal signals (e.g., reduced insulin signaling, increased leptin) and metabolic pathways that break down stored energy reserves and maintain blood glucose levels.

Time-of-day signaling by the circadian timing system allows all cells and all systems (nervous, cardiovascular, digestive, etc.) to predict cyclic changes in the environment, anticipate imminent environmental, behavioral or biological patterns, and to preemptively adapt to them.

So, for example, when the sun sets, our tissues “know” that we will soon go to sleep and be fasting, so energy will need to be pulled out of storage; likewise, when the sun rises, our tissues “know” that we will soon be awake and feeding, so some energy can be stored away to get us through the night.

How Does the Biological Clock Work?

Every cell in our body has some type of autonomous clock that times their activities. In most cells, it is a set of genes called clock genes. Clock genes control the rhythmic activity of other genes to time tissue-specific functions and to generate daily oscillations in cell metabolism and function.

But these tissue-specific clocks need to work coherently to maintain balance in our body. This coherence is created by a master clock in our brain that organizes all circadian processes. This central clock is located in a region of the hypothalamus called the suprachiasmatic nucleus (SCN).

Clock genes in the SCN set the natural period of our biological clock. Although it’s strikingly close to the 24-hour environmental period (on average, around 24.2 hours), it’s still different enough to allow for desynchronization from the environment. Therefore, it needs to be reset every day. This is done by light, the “time giver” that entrains our master clock to the environment.

The SCN receives input from neurons of the retina that contain a light sensitive protein called melanopsin. These neurons, called intrinsically photosensitive retinal ganglion cells (ipRGCs), detect the levels of environmental light and reset the SCN clock to synchronize it with the light-dark cycle.

The SCN can then entrain all cellular clocks to the light cycle. One of the main mechanisms of whole-body clock synchronization is through time-of-day-dependent hormonal signaling. Hormones can carry messages long-distance through the blood and are, therefore, a key communication system in circadian biology. There are two hormones that have a key role in this signaling: melatonin and cortisol.

Melatonin Signals Darkness

The hormone melatonin is a major signaling molecule of the circadian timing system. Melatonin is produced by the pineal gland in a circadian rhythm: It rises soon after sunset (the dim light melatonin onset), peaks in the middle of the night, (between 2 and 4 a.m.), and decreases gradually thereafter, dropping to very low levels during daylight hours.

Melatonin production by the pineal gland is activated by the SCN, via a neuronal signaling pathway that is active only at night. During daytime, light input from the retina inhibits SCN signaling to the pineal gland and stops melatonin synthesis. Through this mechanism, melatonin production is inhibited by light and enhanced by darkness.

Pineal melatonin is released into the blood flow and reaches all tissues in our body, where it modulates the activity of clock genes and acts as a time giver that signals darkness. Through its action in the brain and peripheral tissues, melatonin promotes sleep and shifts our physiological processes into biological night in anticipation of the fasting period.

One of the targets of melatonin is the SCN itself, where it acts as a feedback signal that adjusts the rhythm of the central clock and keeps the whole system running in sync.

Therefore, melatonin is a chronobiotic molecule — a molecule with the capacity to adjust (anticipate or delay) the phase of the biological clock. Melatonin’s chronobiotic effects are vital for the adequate daily rhythmicity of physiological and behavioral processes that are essential for our environmental adaptation.

Cortisol Signals Awakening

The hormone cortisol is mostly known for its action as a stress hormone, but it is also an important signaling molecule in the circadian timing system. Cortisol is produced by mitochondria in the adrenal gland with a circadian rhythm that is controlled by the SCN.

Within the first hour after awakening, there is a sharp increase in the production of cortisol — the cortisol awakening response (CAR). Following this morning peak, cortisol production decreases continuously throughout the day. Cortisol production is very low during the first half of sleep and then rises steadily during the second half.

The surge in cortisol levels during dawn allows the body to: 1) anticipate that we’ll soon wake up after fasting overnight; and 2) prepare for physical activity and feeding. Cells respond by getting ready to process nutrients, respond to energy demands and replenish energy reserves.

The morning peak in cortisol secretion can be regarded as a kind of stress response to waking up that jump-starts our day. The spike in cortisol increases arousal, initiates our biological day and activates our diurnal behaviors.

Disruptions of Circadian Timing

Circadian rhythmicity is very elegantly regulated by the levels and type of light. For example, melatonin production is most markedly inhibited by bright blue light, in which morning light is enriched. And accordingly, the cortisol awakening response is influenced by awakening time and is greater when there is exposure to blue light specifically in the morning.

Our body is optimized to follow the environmental 24-hour pattern, but technology and modern lifestyles have disrupted the pattern. Bright blue light is also a type of light that is emitted in high amounts by artificial light sources, including screens and energy-efficient lightbulbs. Nocturnal exposure to these light sources, even at relatively low light intensities, such as the normal room light, can quickly inhibit melatonin production.

These artificial changes in the circadian timing system are not without consequences. Although the SCN can reset fairly quickly in response to circadian disruption, peripheral organs are slower, which can lead to a desynchrony with the environment if shifts in the light–dark cycle are repeated.

Circadian disruption can have a negative impact on all types of biological processes: It can contribute to sleep disorders, metabolic and cardiovascular dysfunctions, mood disorders and other disruptions that affect well-being.

Shift workers are a commonly used example of how serious circadian misalignment can be: They show misalignment of melatonin and cortisol rhythms, and they have an increased risk of developing cardiometabolic diseases, cancer, and gastrointestinal disorders, among other illnesses.

Final Thoughts

As the understanding of chronobiology grows, so does the awareness of just how important circadian rhythms are for health. The main causes of circadian disruption are changes in our major cycles: the light–dark, sleep–wake, and feeding–fasting cycles.

Therefore, as much as your life allows it, try to create simple habits that may support your circadian rhythms: optimize your sleep, stay away from screens before sleep or use blue light blocking glasses at night, when watching TV or using computers, eat at regular times and earlier in the day, and go outside in the morning and get some bright sunlight.

Sara Adaes, Ph.D., is a neuroscientist and biochemist working as a research scientist at Neurohacker Collective. Sara graduated in Biochemistry at the Faculty of Sciences of the University of Porto, in Portugal. Her first research experience was in the field of neuropharmacology. She then studied the neurobiology of pain at the Faculty of Medicine of the University of Porto, where she got her Ph.D. in Neuroscience. In the meantime, she became interested in science communication and in making scientific knowledge accessible to the lay society. Sara wants to use her scientific training and skills to contribute to increasing the public understanding of science.