How Do Circadian Rhythms Affect Human Health?

Humans are generally most active during the day, making us diurnal creatures. Many people spend daylight hours on essential tasks such as eating, exercising, and socializing, while at night, we use sleep to heal and recharge. As a result, our bodies are in a constant state of flux over the course of a 24-hour day—turning different biological processes on and off to prioritize what functions we need at a given time.

Courtesy of Dr. John Brooks II

Emerging studies have revealed that this internal timing mechanism, known as a circadian clock, is essential to health. Dr. John Brooks II leads research in his lab at Princeton University to explore how our circadian clock directs the immune system and the impact of this regulation on our susceptibility to infection. The 2023 Pew biomedical scholar is uncovering how these systems work together, hoping to discover new avenues for disease prevention and treatment.

This interview was edited for length and clarity.

What are you working on in the lab?

Our research focuses on how the circadian clock regulates immune functions. Because human physiology follows a daily rhythm, we and others have found that immune defenses also rise and fall throughout the day. We have focused our efforts on understanding how internal biological clocks coordinate both immune cell function and tissue protection to determine when the body is most resistant, or most vulnerable, to infection. Understanding these time-of-day effects may reveal new strategies to improve therapies that target both bacterial and viral pathogens and optimize when they are delivered.

Why is our circadian clock so important to health?

It plays a key role in keeping us healthy by helping our bodies tailor metabolic needs to the biological systems that are necessary at a given time. For example, our immune system tends to be more robust during the day, when we’re exposed to the most threats, and less active during the night.

What happens if our lifestyle doesn’t align with this rhythm?

We no longer live in a society where everyone goes to sleep when the sun goes down, so now we need to think about health risks as they occur during the night. For example, shift workers often have a desynchronized internal clock because of schedules that might have them working nights or early mornings. As a result, this population is much more susceptible to infections than people who don't engage in shift work. Studies have shown that they're more likely to develop diabetes and other metabolic syndromes, including obesity-related disorders. This tells us there’s some sort of attunement between the circadian clock of immunity and metabolism.

Does time of day affect if we get sick?

Yes. Because the circadian clock regulates immune functions at precise times, we are likely much more resistant to pathogens based on the time we are infected. Collaborating with Dr. Julie Pfeiffer, a 2007 Pew scholar at UT Southwestern Medical Center, we found evidence that mice are more resistant to gastrointestinal viral infection during the day than they are in the evening. This regulation depends on circadian clock regulation of antiviral genes that coincidently peak during the day and through the evening.

Can we leverage our circadian clock to prevent illness?

Emerging research suggests that maybe we can. For example, researchers have uncovered that there are times during the day when vaccination in mice is more effective because dendritic cells—specialized immune cells—are primed and able to perform their duties more effectively. There might be a future in which you’re only receiving vaccines at these peak opportune times to maximize protective benefits.

What about disease treatment?

We have this concept of “time therapeutics,” which explores leveraging our circadian rhythm to help our body fight disease more effectively, but the mechanisms by which this would work are not yet well defined.

Do scientists factor time of day in studies?

As scientists, we often don’t consider the time of day of infection or vaccination in our research, but we're finding that the time really does matter. I think in the near future, to make a lot of the research we do more replicable, we'll have to start defining infection time in our experiments.

What could this mean for the future of biomedical research?

If we start accounting for time in our studies, I believe we'll begin seeing very interesting results. Ultimately, recording time could transform the infectious disease space in the same way that the discovery of the microbiome changed how we understand every other biological system—by revealing foundational insights into human health.