Circadian rhythmicity and human health

Abstract

Our modern lifestyle involves irregular eating habits and extended periods spent indoors under artificial lighting. This lifestyle contrasts with the body's circadian rhythms and likely contributes to an increase of chronic diseases worldwide. This special issue on the circadian rhythm contains articles that deepen our understanding of the biological rhythmicity associated with health and disease. Research articles include studies on the effects of light therapy in patients with myocardial infarction and 24-h ambulatory blood pressure monitoring in Japanese women. Review articles cover the roles of micro-RNAs in colorectal cancer, the influence of light, electromagnetic fields and water on biological rhythms, and the effects of eating patterns on metabolic diseases. These studies and review articles highlight the importance of maintaining circadian rhythms and provide practical tips to improve human health.

We rarely consider whether our brain, immune and metabolic functions are properly synchronized and happening at the right time of day, even though these physiological functions are controlled by a circadian clock that keeps time throughout our cells and organs [[1], [2], [3]]. More than a mere regulator of the sleep-wake cycle, the circadian rhythm regulates a wide range of body functions, from hormone secretion, metabolism, and immunity, to energy homeostasis, physical coordination, and body repair [[1], [2], [3]] [Fig. 1]. The circadian rhythm synchronizes physiological functions with the time of day to prepare the body for changes in the environment and favor optimal energy use and functioning.

Fig. 1.

Human activities and the circadian rhythm.

The body's clock has critical implications for human health since suboptimal function and inflammation arise when cells and organs fall out of sync [1,4]. This disruption can occur, for instance, following sleep deprivation, night shift work and travel across several time zones. In the long term, circadian disruption alters various physiological processes and therefore may contribute to the development of chronic diseases such as type 2 diabetes, cardiovascular disease, cancer, and neurodegeneration [1,2]. For the same reason, interventions that aim to maintain or restore circadian rhythmicity have the potential to prevent and treat a wide range of disease conditions.

Throughout evolution, the main pacemaker of human activities has been the Sun. However, the modern human lifestyle shifted towards spending long hours indoors under artificial lighting. Studies suggest that people who maintain active Sun exposure habits have a lower incidence of cancer, hypertension, cardiovascular disease, multiple sclerosis, Alzheimer's disease, and myopia, ultimately living longer and healthier lives [5,6]. The beneficial effects of the Sun are likely due to its infrared and ultraviolet light radiation, whose importance is becoming increasingly clear.

In this special issue on the circadian rhythm, Chin et al. performed a randomized controlled trial to determine the effects of blue light therapy for people with myocardial infarction [7]. The results showed a trend towards better active-rest rhythms in the group receiving blue light therapy, but the results did not reach statistical significance. Blue light therapy was associated with higher levels of vitamin D, a surprising finding given that production of the ‘D-lightful’ hormone requires ultraviolet light [8]. While the results are preliminary and were limited by the settings of the intensive care unit, they suggest that patients with myocardial infarction display sleep disturbances and circadian disruption that may benefit from light therapy. In future studies, it would be interesting to see how these patients fare after spending more time in natural sunlight.

Herichová describes her findings related to the roles of small non-coding micro-RNAs (miRNAs) in colorectal cancer [9]. She observed that many miRNAs that are upregulated in colorectal cancer tissues may act by inhibiting the activity of tumor suppressing genes such as phosphatase and tensin homolog (PTEN) and p53. Surprisingly, differences were observed in miRNA in colorectal cancer tissues in men and women, with men showing upregulation of miRNAs associated with the clock genes per2 and cry2, whereas this phenomenon did not occur in women.

Martel and colleagues explain that our environment, saturated with blue-enriched lights and screens—from televisions, smart phones, tablets, and computers—can disrupt circadian rhythms and negatively impact health [10]. Non-native electromagnetic fields (EMFs) from wireless devices, cell phones, and the recent expansion of low Earth orbit internet satellites are likely to affect biological rhythms in unexpected ways. The authors review possible mechanisms underlying these effects, which include ion cyclotron resonance and effects on the electron spin of radical pairs. They also describe the roles of intracellular water based on the concepts of coherent domains and exclusion zone, which is expected to provide a fresh perspective on cellular functions [10].

The arguments presented in these articles lead to various practical recommendations to improve circadian rhythmicity and health [10], which, as previously described, calls for a return to a more natural lifestyle, distancing from modern technology [11,12]. Unfortunately, with large companies and society nowadays moving towards more materialistic values, artificial intelligence (AI), the Internet of Things (IoT), the Internet of Bodies (IoB), and more electromagnetic pollution, we can expect a further decline of human health―a deterioration that has been even more obvious with the Covid-19 pandemic.

One of the fathers of chronobiology, Franz Halberg (1919–2013), once observed that physiological functions show opposite results depending on the time of measurement during the day and night [13]. Germaine Cornelissen—who collaborated for a number of years with Halberg and is now the Director of the Halberg Chronobiology Center at the University of Minnesota—performed several studies involving time-series measurements. In their latest work, Cornelissen, Otsuka and colleagues performed a continuous 24-h monitoring of blood pressure and heart rate in women living in a rural area in Japan [14]. Subjects with a clear 12-h period showed fewer vascular disorders than those with shorter or longer periods. The authors also identified abnormal blood pressure patterns, such as excessive activity at night and surpassing the upper threshold during the day, which may help identify people at risk of cardiovascular events.

Chiesa et al. review the mechanisms underlying the effects of eating patterns on the development of chronic diseases including obesity, type 2 diabetes, immune disruption, cancer and cognitive decline [15]. The authors show that light exposure and eating out of sync with the circadian rhythm alter the entrainment between the suprachiasmatic nucleus (SCN) and peripheral clocks, which in turn can affect the gut microbiota and contribute to alter the function of various organs. Notably, the review presents recent studies linking circadian disruption with mood disorders. Consistent with the ideas expressed in this review, a study [16] recently published in Biomedical Journal shows that constant light increases weight gain, insulin resistance, and white fat accumulation and disrupts the circadian rhythm in mice, which can be partially reversed with chronic low doses of a synthetic compound called SR9009, or stenabolic.

Several practical applications emerge from the original reports and reviews presented in this special issue. The human body requires plenty of sunlight and evidence suggests that most people do not get enough. Exercising in the evening and avoiding late snacks might help to improve insulin sensitivity and overall health. The timing and quality of indoor lighting and a reduction of wireless devices also need to be considered. The time is ripe to pay more attention to our biological rhythms!