The immune system is under circadian control. Disrupting the biological clock by working night shifts can increase the susceptibility to diseases.
As the streets grow quiet and the world falls asleep, some people continue their daily grind: Hospitals buzz with nurses on rounds, highways roar with truckers speeding by, and call centers hum with voices handling overseas clients.
Nearly 18 percent of American and 20 percent of European laborers work alternate shift schedules, which could adversely affect their health.1,2 In fact, people who work night shifts take more sick leave compared to those who work during regular hours.3
Christoph Scheiermann studies circadian oscillations in the immune system at the University of Geneva.
© Swiss Cancer League
“If you don’t live and work and eat in sync with your environment, you desynchronize your body to the external cues that are normally physiologically there,” said Christoph Scheiermann, a circadian immunologist at the University of Geneva.
This leads to a misalignment between one’s sleep-wake cycle and their body’s biological clock, which controls physiological functions like metabolism, endocrine activity, and immunity. Disrupting it by disturbing the natural sleep-wake cycle can increase the risk of cardiometabolic and autoimmune disorders as well as some cancers. Studying the molecular and genetic mechanisms underlying this phenomenon helped scientists better understand how circadian rhythm components influence health and develop approaches to avoid diseases in night workers.
Working Nights is Linked to Adverse Health Outcomes
Until the mid-20th century, people would stick to working conventional times during the weekdays. As technologies and economies developed, organizations extended working hours, which led to increasingly nonstandard job schedules.
By the 1980s, epidemiologists observed a link between shift work and higher rates of ulcers, digestive issues, and cardiovascular diseases.4,5 Follow up studies revealed that the risk of developing such disorders shot up with increasing time spent working nights.6
Eventually, scientists also observed a link between night shift work and metabolic diseases, infections, autoimmune disorders, cancers, and menstrual disorders.7,8 A recent study also found that compared to day workers, night shift workers showed accelerated biological aging as measured using clinical biomarkers.9
Studying Circadian Disruption Using Animal Models
While epidemiological data provided clues about links between circadian rhythms and disease, studying the underlying molecular mechanisms in humans is challenging. However, experiments using animal models revealed that both innate and adaptive arms of the immune system are under circadian control: Cells from both systems—including monocytes, macrophages, neutrophils, and T and B cells—have intrinsic clocks that regulate their function and activity.10 In line with this, some researchers found varied patterns of cytokines in the saliva of people who worked day and night schedules.11
Scheiermann explained that to explore the effect of circadian rhythm disruption, researchers in the field usually start out by identifying molecules that exhibit cyclical activity or expression. To assess whether the oscillation is responsible for a function, “We often use [a] functional intervention technique with an antibody or with a small inhibitor of specifically that molecule,” he said.
Disrupting components of the circadian system in animal models have offered insights into the factors that control cyclical recruitment of immune cells.12 Such studies, in combination with epidemiological data, have provided crucial information on why circadian disruption increases disease susceptibility.
“In general, what is known is that if you work night shifts…you are immunocompromised, [or] immunosuppressed,” said Scheiermann. “Overall, then this would expose you to a higher risk of infections and then also cancer.”
Managing Internal Circadian Misalignment
Despite the evidence, night shift workers remain an essential part of everybody’s lives: Doctors, nurses, airline staff, and many other professionals are integral to the functioning of essential services around the clock. Given this, those who work outside the conventional hours could build a few habits that reduce their disease susceptibility.
Light and dark are important environmental cues that entrain the circadian rhythm, which is disrupted in night workers. “One of the general things apart from light and darkness [for night shift workers] is to maybe be able to arrange other cues that allow the circadian system to be working properly,” said Scheiermann.
One such important cue is meal timings. “So, what these [people] maybe could still do then is to ideally design their meal time still during the light phase, so that at least the [digestion] is occurring during the light phase and not really during the night phase,” Scheiermann said.
Indeed, results from animal studies indicate that restricting food intake to the active phase can prevent adverse metabolic effects.13 Consistent with this, in a small trial consisting of 19 participants, scientists found that limiting eating to daytime prevented the spike in blood sugar linked with night shift work.14
Scheiermann added that restricting physical activity to daytime could similarly help align some physiological functions with the environment.
Overall, scientists are increasingly understanding the mechanisms underlying circadian disruption-induced disease risk. For the millions of people working through the night to keep essential services running, such insights could someday help guard their health.
- Strohmaier S, et al. A review of data of findings on night shift work and the development of DM and CVD Events: A synthesis of the proposed molecular mechanisms. Curr Diab Rep. 2018;18(12):132.
- Silva I, Costa D. Consequences of shift work and night work: A literature review. Healthcare. 2023;11(10):1410.
- Larsen AD, et al. Night shift work and sickness absence – Many for the few or few for the many?Eur J Public Health. 2023;33:ckad160.1341.
- Segawa K, et al. Peptic ulcer is prevalent among shift workers. Dig Dis Sci. 1987 May;32(5):449-453.
- Akerstedt T, et al. Shift work and cardiovascular disease. Scand J Work Environ Health. 1984;10(6 Spec No):409-14.
- Knutsson A, et al. Increased risk of ischemic heart disease in shift workers. Lancet. 1986;328(8498):89-92.
- Streng AA, et al. Night shift work characteristics are associated with several elevated metabolic risk factors and immune cell counts in a cross-sectional study. Sci Rep. 2022;12(1):2022.
- Hu F, et al. Shift work and menstruation: A meta-analysis study. SSM Popul Health. 2023;24:101542.
- Cai Y, et al. Night shift work, accelerated biological aging and reduced life expectancy: a prospective cohort study. QJM. 2025:hcaf091.
- Scheiermann C, et al. Clocking in to immunity. Nat Rev Immunol. 2018;18(7):423-437.
- Reinhardt ÉL, et al. Night work effects on salivary cytokines TNF, IL-1β and IL-6. Chronobiol Int. 2019;36(1):11-26.
- Scheiermann C, et al. Adrenergic nerves govern circadian leukocyte recruitment to tissues. Immunity. 2012;37(2):290-301.
- Hatori M, et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012;15(6):848-860.
- Chellappa SL, et al. Daytime eating prevents internal circadian misalignment and glucose intolerance in night work. Sci Adv. 2021;7(49):eabg9910.