Did you know that there are three types of biological clocks that exist within all people? These three types of clocks work together to regulate how our bodies respond to physiological needs over a 24-hour period. Importantly, the relationship between these circadian clocks and our sleep-wake cycle have significant effects on our health.

You’ve got rhythm! Circadian, at least.

In the 1700s, a French scientist put a mimosa plant inside a sealed box and noticed that the leaves continued to open during the day and close at night, despite having no access to sunlight.¹ He thought the plant could ‘sense’ the sun. He was wrong, but his plant-in-a-box endeavor spawned the scientific field of chronobiology. Three hundred years later, we now know that the plant was displaying circadian rhythms that had been synchronized to sunlight, but that continued in the absence of light due to the biological clocks inside the plant cells. 

The sleep/wake cycle is the most obvious example of a circadian rhythm

Circadian rhythms are biological cycles that animals, plants, and even bacteria display over approximately 24 hours. The most obvious circadian rhythm in animals is the sleep/wake cycle, which defines periods of activity versus inactivity. As we’ll discuss, circadian rhythms aren’t passive behaviors (“Oh hey, it’s light outside. Tacos?”). Rather, they reflect a translation of environmental information (e.g., light) into chemical information (e.g., hormones, neurotransmitters) that enables an organism to adapt to its surroundings. 

Along with our sleep/wake cycle, our biological needs also change over a 24-hour period. Billions of chemical reactions occur in the body every second to make these biological functions possible. These reactions require a lot of energy, so they should occur only when needed and in a particular order. There are control mechanisms to ensure that the proper initiation and order of these reactions takes place. One important control mechanism is the biological clock. 

Tick tock, you don’t stop: 3 Biological clocks

1. The master clock is located in the brain

Our bodies keep track of time with biological clocks. As mentioned earlier, there are three types of circadian clocks, and they communicate with each other in a generally hierarchical fashion (figure). At the top of the hierarchy is the master clock, which is located in the brain behind the eyes. It’s called the master clock because it sets the time for the rest of the body. It senses light with its connections to the visual system, and it senses darkness when melatonin is released in the brain. The master clock communicates this light/dark information to the rest of the body through its connections to the autonomic nervous system.

2. Peripheral clocks include the endocrine system and the immune system

Using the autonomic nervous system, the master clock influences the second type of clock, the peripheral clocks. Two major peripheral clocks are the endocrine system and the immune system. When peripheral clocks receive synchronizing information (light/dark) from the master clock, the behavior of the peripheral clock tissue changes. For example, the tissue may switch from producing one type of hormone to another, or it may alter the types of immune cells in circulation. 

Parts of the brain and adrenal glands (the HPA axis) are among the first peripheral clocks to be synchronized to the master clock. When activated, the HPA axis secretes cortisol into the bloodstream; this hormonal signal synchronizes other peripheral clocks. Cyclic cortisol secretion has important implications for how our bodies function on a daily basis, as we’ll discuss later. 

3. Molecular clocks interact with our DNA to turn genes on and off

Both the master clock and peripheral clocks are distinct tissues, each made up of millions to billions of cells. Inside each cell of these tissues is the third type of biological clock, the molecular clock.² The molecular clock is composed of specialized proteins that interact with our genomic DNA to determine which genes get turned on or off. When a peripheral clock tissue receives a synchronizing signal from the nervous system (or from other peripheral clocks stimulated first), the molecular clock responds by turning some genes on and other genes off. This changes the behavior of the cell, which then changes the behavior of the tissue. 

Remember we said that our biological reactions require lots of energy and must occur only when needed and in a specific order? The body ensures that all of these processes work together to promote normal functions by tying these reactions ultimately to the molecular clock (which is synchronized to light/dark). Unfortunately for midnight snackers, this means that eating pizza at midnight is metabolically different from eating it at noon. Keep reading to understand why!

Biological clocks can become misaligned by artificial light from cell phones and eating at night

Keep in mind that the synchrony between the three clocks is made possible by an environmental cue, light. If something interferes with the timing of the light/dark cycle, then the three clocks lose their alignment with each other.² The most common disrupters of circadian rhythms in humans are artificial light at night (cell phones, lamps, TV, etc.) and eating at night, both of which have documented consequences for our health. Other circadian disruptors include night shift work, sleep deprivation, jet lag, and having a weekend sleep schedule different from weekdays. All of these scenarios desynchronize the master clock from the peripheral and molecular clocks.¹

Unfortunately, the misalignment of biological clocks over time can have serious consequences. Misalignment of peripheral endocrine clocks causes hormones to be secreted in amounts that are too low, or when the target tissue is less sensitive to it, which can lead to an unhealthy state.³

For example, we secrete insulin from the pancreas in response to an increase in blood glucose (sugar). Insulin’s major target tissues are the liver and skeletal muscle, which respond to insulin by storing glucose for future use. However, if insulin is released at a time when the skeletal muscles and liver are less sensitive to it (at night), then blood glucose will remain high (hyperglycemia). This is called insulin resistance, and it is a characteristic of type 2 diabetes.

Sleep at night, eat during the day

You don’t need to have a crazy schedule to have misaligned endocrine clocks. Even during short periods of misalignment, healthy people can experience reversible changes in insulin resistance and inflammation.⁴ In fact, just three days of eating at night and sleeping during the day can result in higher fasting blood glucose and fasting free fatty acids, two markers for prediabetes.⁵ Incredibly, eating exactly the same meal at night versus during the day results in hyperglycemia and weight gain, regardless of sleeping habits.⁶ All of this means that humans were built to sleep at night, not eat.