Circadian rhythm – the body’s ‘clock’ – controls our sleep-wake cycle. Whether you’re a morning person or a ‘night owl’ is a behavioral consequence of how your genes affect your ‘body clock’. If this clock is virtually out of time, the consequences are clear: jet lag, for example, is the manifestation of a disrupted circadian rhythm.
But the circadian rhythm, a 24-hour biological process that aligns our bodies with the rotation of the earth, also controls metabolism, body temperature, hormones, and the immune system. Various health conditions and diseases in turn display a ‘circadian component’ and can in some cases be a direct result of faulty circadian clocks.
In a study published in the journal on Tuesday Genome research, scientists report the circadian rhythm affects our ability to fight disease to a greater extent than previously realized. The research represents a new understanding of an ancient process – and provides a striking reminder that good “sleep hygiene” is critical to health, far better than feeling well rested.
Why it matters – Finally, research suggests that tracking circadian rhythms is key to understanding how the body protects against 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. Her research focuses on the fundamental mechanisms under circadian rhythms, and how they affect human health. She tells Reverse that scientists have already known chronic disruption of the circadian clock over a lifetime may lead to an increased risk for certain diseases, ranging from cancer to heart disease. What was not known, however, is how this disruption leads to an increased risk.
“We’ve noticed that all of the diseases associated with chronic circadian disruption are also linked to inflammation, which is a product of the immune system,” Hurley explains.
However, a deep understanding of how the clock controls the immune system in cells or organisms does not exist. This study aimed to fill that gap in knowledge. ”
What is the circadian rhythm?
Every cell in the body has its own biological clock. These small timers are coordinated by a central clock in the brain called the suprachiasmatic nucleus, or SCN. It controls and synchronizes the circadian rhythm while keeping everything in time with the Earth’s rotation. Circadian rhythms occur in almost every earthly organism – even plants are stimulated by a circadian rhythm to open their leaves during the day and close at night.
Circadian rhythms play a role in many of the processes underlying immunity, and chronic circadian disruption is associated with an increased risk of metabolic, cardiovascular, and neurodegenerative diseases. These health issues all 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 disease and circadian rhythm.
Dr. Jennifer Hurley explains her circadian rhythm investigation.
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 such as bacteria – play an important role in the “intuition, maintenance and resolution of both acute and chronic inflammation. According to the study, macrophages can have a major influence on the functioning of circadian clocks, as they live in the bloodstream for months.
Macrophages, Hurley and her team discovered, change over time in their responses to both pathogens and stress through circadian metabolic control. But the exact nature of their timing was completely unexpected, Hurley says.
“We’ve learned that the circadian control mechanisms in the cell are more complex than we previously believed, which means there are probably more that control circadian rhythms than we knew,” Hurley says.
“Our study has a lot of potential to advance science.”
Go into the details – To understand the study, Hurley explains, one must know that the ‘central dogma of biology’ is that DNA (our genes), RNA (gene transcripts) and proteins (the ‘actors’ of the cell) make.
“As a field, we draw conclusions about what the circadian clock did in the body by looking at the transcripts as a proxy for which proteins had a circadian rhythm,” says Hurley.
“As a protein biochemist, however, I know that a lot happens when transcripts are made into proteins and that, just by looking at the transcripts, we will miss a lot of what is going on in the cell.”
The study team specifically investigated the change in levels of RNA and macrophage proteins over two days – 80 percent of the circadian proteins were found. do not have has a transcription that also had a circadian rhythm. Subsequent analysis also revealed the interaction between the circadian rhythm and metabolism, essentially the macrophages’ immune functions – a process that results from the cleavage 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 your circadian rhythm help fight disease?
According to Hurley: “Absolutely!”
The most important thing people can do, she explains, is to exercise good sleep hygiene. It can be divided into three components:
- Sleep eight hours a night
- Do not expose yourself to bright lights at night
- Keep a regular daily schedule so you can 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,” Hurley says. In other words: put down your smartphone or tablet before going to bed at night.
Knowing how the immune system responds to diseases is important in finding ways to combat those challenges. Here, the research team found an invaluable 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 go wrong or intensify.
In the future, Hurley hopes the study “can help others learn what these new mechanisms are and how they work.”
Abstract: Our core time mechanism, the circadian clock, plays an important role in immunity. Although the mechanics of circadian control over the immune response are generally explained by transcriptional activation or suppression derived from the transcriptional translation negative feedback loop of this clock, research suggests that some regulations occur outside of transcriptional activity. We fully profiled the transcriptome and proteome of murine bone marrow-derived macrophages and found that only 15% of the circadian proteome had corresponding oscillating mRNA, indicating that regulation after transcription has a greater influence on the macrophage clock regulatory output than any other tissue which was previously profiled. This regulation can be explained by the strong temporary enrichment we have identified for proteins involved in degradation and translation. Extensive post-transcriptional temporal gating of metabolic pathways has also been observed and is further consistent with daily variations in ATP production, mitochondrial morphology, and phagocytosis. The disruption of this circadian metabolic regulation after transcription impaired immune functionality. Our results show that cell-intrinsic post-transcriptional regulation is a primary driver for circadian output in macrophages, and that this regulation, especially metabolic pathways, plays an important role in determining their response to immune stimuli.