Circadian Rhythms


Circadian rhythms (“circa” meaning about and “dia” meaning a day) are 24h rhythms that govern a wide variety of behaviors and cellular processes such as sleep wake cycles, immune function, and intestine and liver function. The circadian system allows an organism to synchronize (i.e., entrain) biological functions to predictable changes in the environment such as light exposure and food consumption.

Circadian rhythms are generated by the molecular circadian clock, which is found in nearly every cell in the mammalian body. This molecular clock is orchestrated by the cyclic expression of clock genes, which takes approximately 24h to complete. The molecular circadian cycle is initiated when the CLOCK and BMAL1 combine (i.e., heterodimerize) to stimulate the transcription of target circadian genes, including period (Per) and cryptochrome (Cry) as well as other genes known as clock-controlled genes. When PER and CRY proteins accumulate in the cytosol, they heterodimerize and translocate to the nucleus where they act as transcriptional repressors to terminate CLOCK-BMAL1–mediated transcription to end the cycle. Several other proteins (e.g., sirtuin 1 (SIRT1)) fine tune the molecular circadian clock, but the core circadian clock is comprised of CLOCK, BMAL1, PER, and CRY.

The central circadian clock (i.e., “pacemaker”) is located in the suprachiasmatic nucleus (SCN) in the hypothalamus in the brain. The central circadian clock is regulated by light and fulfills the role of a conductor of the orchestra, in essence directing circadian clocks in the periphery (i.e., peripheral clocks) including in the immune system, pancreas, intestine, and liver, just to name a few. In addition to being regulated by the central circadian clock, peripheral circadian rhythms can also be regulated by other factors. For example, time of eating robustly regulates circadian rhythms in the intestine and liver.

Circadian clocks regulate 5-20% of the genome (i.e., so-called clock-controlled genes) with 3-20% of the genome demonstrating 24-hour oscillations in gene expression. It should not be surprising then that disrupting the circadian clock and the resulting effect on circadian rhythms can wreak havoc on the homeostasis of the mammalian body including cell, tissue, and whole organism function.

Our modern-day society includes a plethora of environmental conditions and factors that can disrupt circadian rhythms such as light exposure at night, including street lights (i.e., light pollution) and the use of light-emitting devices at night, late-night eating or irregular eating patterns, night shift work, traveling across time zones, and social jet lag where sleep/wake cycles are adjusted to accommodate social demands. Disruption of circadian rhythms can manifest in humans as chronic health conditions, such as metabolic syndrome, diabetes, cardiovascular disease, cancer, and intestinal disorders.

Circadian rhythms may also influence the effects of alcohol on the tissues in the body. For example, the time of alcohol consumption can influence the impact on the body, administering alcohol to mammals with circadian rhythm disruption are more sensitive to the effects of alcohol, and alcohol itself can disrupt circadian rhythms. A better understanding of these mechanisms and unveiling other as yet unknown phenomena can only be achieved by the concerted efforts of talented investigators. Developing a better mechanistic understanding of the interaction between circadian rhythms and alcohol consumption is expected to reveal new therapeutic strategies and screening approaches to prevent and treat alcohol-induced pathologies.