Circadian rhythm – the body’s ‘clock’ – governs our sleep-wake cycle. Whether you are a morning or night person, it is a behavioral consequence of how your genes affect your “biological clock”. When that clock is out of time, so to speak, the effects are obvious: jet lag is the manifestation of an interrupted circadian rhythm, for example.
But circadian rhythm, a 24-hour biological process that aligns our bodies with Earth’s rotation, also controls metabolism, body temperature, hormones and the immune system. Various health conditions and diseases, in turn, have a “circadian component” and, in some cases, can be a direct consequence of defective circadian clocks.
In a study released Tuesday in the journal Genome Research, scientists report circadian rhythm influences our ability to fight disease to a greater degree than previously thought. The research represents a new understanding of an old process – and offers an important reminder that good “sleep hygiene” is fundamental to health, far beyond feeling well rested.
Why does it matter – Ultimately, the research suggests that accurate tracking of circadian rhythms is the key to understanding how the body protects itself from disease. By changing your approach to sleep, you can dramatically change the course of your health.
Lead author Jennifer Hurley is an assistant professor at the Rensselaer Polytechnic Institute. His research focuses on the fundamental mechanisms underlying circadian rhythms and how they affect human health. She says Inverse that scientists already knew that chronic interruptions of the circadian clock throughout life can lead to an increased risk of certain diseases, ranging from cancer to heart disease. What was not known, however, is how this interruption leads to an increased risk.
“We found that all diseases associated with chronic circadian disorders were also linked to inflammation, which is a product of the immune system,” explains Hurley.
“However, there was no deep understanding of how the clock controls the immune system, in cells or organisms. This study aimed to help fill this knowledge gap. “
What is the circadian rhythm?
Each cell in the body has its own biological clock. These tiny chronometers are coordinated by a central clock in the brain, called the suprachiasmatic nucleus, or SCN. It controls and synchronizes the circadian rhythm while maintaining everything in time with the Earth’s rotation. Circadian rhythms are found in almost all terrestrial organisms – even plants are stimulated by a circadian rhythm to open their leaves during the day and close them at night.
Circadian rhythms influence many of the processes underlying immunity, and chronic circadian disturbance is associated with an increased risk of metabolic, cardiovascular and neurodegenerative diseases. All of these health problems share underlying inflammatory components – which is why there is a hypothesis that dysregulation of immunity, which can manifest itself as chronic inflammation, for example, may be the link between the disease and the circadian rhythm.
Dr. Jennifer Hurley explains her research on circadian rhythm.
The so-called “gears” of biological clocks are genes and proteins, while macrophages – white blood cells of the immune system that detect and destroy harmful invasive organisms like bacteria – play a vital role in “intuition, support and resolution of acute and chronic inflammation” , according to the study.The authors argue that macrophages can exert an extraordinary influence on the functioning of circadian clocks, since they live for months in the bloodstream.
Macrophages, Hurley and his team discovered, temporal changes in their responses to pathogens and stress through circadian control of metabolism. But nature needs its time was totally unexpected, Hurley says.
“We learned that the circadian control mechanisms in the cell are more complex than we previously believed, which means that there is likely to be more control of the circadian rhythm than we knew,” says Hurley.
“Our study has a lot of potential for advancing science.”
Exploring the details – To understand the study, explains Hurley, it is necessary to know that the “central dogma of biology” is that DNA (our genes), makes RNA (transcriptions of genes) and proteins (the “actors” of the cell).
“As a field, we were making inferences about what the circadian clock did in the body, looking at the transcripts as a proxy for which proteins had a circadian rhythm,” says Hurley.
“However, as a protein biochemist, I know that a lot happens when the transcripts are made in proteins and that, just by looking at the transcripts, we would lose a lot of what was happening in the cell.”
Specifically, the study team examined how the levels of macrophage RNA and proteins changed over the course of two days – finding 80 percent of circadian proteins did not has a transcript that also had a circadian rhythm. Subsequent analysis also revealed the interaction of circadian rhythm and metabolism essentially with the immune functions of macrophages – a process that results from the division and fusion of mitochondria.
The team also found proteins involved in Covid-19 infection have a circadian rhythm, “which may play an important role in the immune response to this viral infection,” says Hurley.
Can you help your circadian rhythm to fight disease?
According to Hurley: “Absolutely!”
The first thing people can do, she explains, is to practice good sleep hygiene. This can be divided into three component parts:
- Sleep eight hours a night
- Not exposing yourself to bright lights at night
- Maintain a regular daily schedule to wake up naturally, without an alarm clock
“The key to all of this is to avoid exposure to bright light at night, which can really disrupt your circadian rhythm,” says Hurley. In other words: put your smartphone or tablet on the table before going to bed at night.
Understanding how the immune system responds to disease is the key to finding ways to fight these challenges. Here, the study team has discovered an unappreciated way in which the body works to protect itself from disease – and how certain habits and actions we take can cause these defense mechanisms to become damaged or strengthen.
In the future, Hurley hopes that the study “can help others learn what these new mechanisms are and how they work”.
Abstract: Our main timing mechanism, the circadian clock, plays a vital role in immunity. Although the mechanics of circadian control over the immune response is generally explained by the transcriptional activation or repression derived from the negative feedback cycle of the clock’s transcription-translation, research suggests that some regulation occurs beyond transcriptional activity. We detailed the transcriptome and proteome of murine bone marrow-derived macrophages and found that only 15% of the circadian proteome had a corresponding oscillating mRNA, suggesting that post-transcriptional regulation influences the regulatory output of the macrophage clock to a greater extent than any other previously profiled fabric. This regulation can be explained by the robust temporal enrichment that we have identified for proteins involved in degradation and translation. Extensive post-transcriptional temporal passage of metabolic pathways was also observed and still corresponded to daily variations in ATP production, mitochondrial morphology and phagocytosis. The interruption of this post-transcriptional circadian metabolic regulation impaired immune functionality. Our results demonstrate that intrinsic cellular post-transcriptional regulation is the main driver of circadian production in macrophages and that this regulation, particularly of metabolic pathways, plays an important role in determining its response to immune stimuli.