"A deep understanding of how the clock controls the immune system, in cells or in organisms, didn’t exist."

Get Rhythm

Fight off disease by making this one change to your nighttime routine

In a study released Tuesday in the journal "Genome Research," scientists report circadian rhythm influences our ability to fight off diseases.

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Circadian rhythm — the body's 'clock' — governs our sleep-wake cycle. Whether you are a morning person’ or a ‘night owl’ is a behavioral consequence of how your genes affect your 'body clock.' When this clock is out of time, so to speak, the effects are obvious: jet lag is the manifestation of a disrupted circadian rhythm, for example.

But the circadian rhythm, a 24-hour biological process which aligns our bodies with Earth’s rotation, also controls metabolism, body temperature, hormones, and the immune system. Various health conditions and diseases, in turn, display a “circadian component,” and, in some cases, may be a direct consequence of faulty circadian clocks.

In a study released Tuesday in the journal Genome Research, scientists report the circadian rhythm influences our ability to fight off diseases to a greater degree than previously realized. The research represents a new understanding of an ancient process — and offers a salient reminder that good "sleep hygiene" is critical to health far beyond feeling well-rested.

Why it matters — Ultimately, the research suggests accurately tracking circadian rhythms is key to understanding how the body protects against diseases. By changing your approach to sleep, you may be able to dramatically change the course of your health.

Lead author Jennifer Hurley is an assistant professor at Rensselaer Polytechnic Institute. Her research focuses on the fundamental mechanisms underlying circadian rhythms, and how they affect human health. She tells Inverse that scientists already knew chronic disruptions to the circadian clock over a lifespan can lead to increased risk of certain diseases, ranging from cancer to heart disease. What wasn’t known, however, is how this disruption leads to an increased risk.

“We had observed that all of the diseases that were associated with chronic circadian disruption were 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 in organisms, didn’t exist. This study aimed to help fill that gap in knowledge.”

What is the circadian rhythm?

Every cell in the body has its own biological clock. These tiny 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 are found in almost every terrestrial organism — even plants are prompted by a circadian rhythm to open their leaves during the day and close them at night.

Circadian rhythms have a hand in many of the processes underlying immunity, and chronic circadian disruption is linked to an increased risk for metabolic, cardiovascular, and neurodegenerative diseases. These health issues all share underlying inflammatory components — which is why there’s a hypothesis that dysregulation of immunity, which can manifest as chronic inflammation, for example, may be the link between disease and circadian rhythm.

Dr. Jennifer Hurley explains her circadian rhythm research.

The so-called “cogs” 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 the “intuition, sustainment, and resolution of both acute and chronic inflammation,” according to the study. The authors reason macrophages may wield an outsize influence on the functioning of circadian clocks, as they live for months at a time in the bloodstream.

Macrophages, Hurley and her team discovered, time changes in their responses to both pathogens and stress via the circadian control of metabolism. But the precise nature of their timing was wholly unexpected, Hurley says.

“We learned the circadian control mechanisms in the cell are more complex than we previously believed, meaning that there is likely more that circadian rhythms control than we knew,” Hurley says.

“Our study has a lot of potential to forward science.”

Digging into the details — To understand the study, Hurley explains, one needs to know that the “central dogma of biology” is that DNA (our genes), makes RNA (gene transcripts) and proteins (the “actors” of the cell).

“As a field, we were making inferences about what the circadian clock did in the body by looking at the transcripts as a proxy for which proteins had a circadian rhythm,” Hurley says.

“However, as a protein biochemist, I know that a lot happens when transcripts are made into proteins and that by only looking at the transcripts, we would miss a lot of what was going on in the cell.”

Specifically, the study team examined how macrophages’ levels of RNA and proteins changed over two days — finding 80 percent of the circadian proteins did not have a transcript that also had a circadian rhythm. Subsequent analysis also revealed the interplay of the circadian rhythm and metabolism essentially times the macrophages’ immune functions — a process that results from the splitting and fusing of mitochondria.

The team also found proteins involved in Covid-19 infection have a circadian rhythm, "which could play an important role in the immune response to this viral infection," Hurley says.

Can you help your circadian rhythm fight disease?

According to Hurley: “Absolutely!”

The number one thing people can do, she explains, is practice good sleep hygiene. This can be broken down into three component parts:

  1. Sleeping eight hours a night
  2. Not exposing oneself to bright lights at night
  3. Keeping a regular daily schedule so you wake up naturally, without an alarm clock

“Key to all of this is avoiding exposure to bright light at night, which can really perturb your circadian rhythm,” Hurley says. In other words: Put your smartphone or tablet down before you get into bed at night.

Understanding how the immune system responds to disease is key to finding ways of fighting those challenges. Here, the study team found an unappreciated way the body works to safeguard itself against disease — and how certain habits and actions we take can cause these defense mechanisms to go awry, or strengthen.

In the future, Hurley hopes the study “can help others learn what these novel mechanisms are and how they work.”

Abstract: Our core timekeeping mechanism, the circadian clock, plays a vital role in immunity. Although the mechanics of circadian control over the immune response is generally explained by transcriptional activation or repression derived from this clock's transcription-translation negative-feedback loop, research suggests that some regulation occurs beyond transcriptional activity. We comprehensively profiled the transcriptome and proteome of murine bone marrow-derived macrophages and found that only 15% of the circadian proteome had corresponding oscillating mRNA, suggesting post-transcriptional regulation influences macrophage clock regulatory output to a greater extent than any other tissue previously profiled. This regulation may be explained by the robust temporal enrichment we identified for proteins involved in degradation and translation. Extensive post-transcriptional temporal-gating of metabolic pathways was also observed and further corresponded with daily variations in ATP production, mitochondrial morphology, and phagocytosis. The disruption of this circadian post-transcriptional metabolic regulation impaired immune functionality. Our results demonstrate that cell-intrinsic post-transcriptional regulation is a primary driver of circadian output in macrophages and that this regulation, particularly of metabolic pathways, plays an important role in determining their response to immune stimuli.

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