For many individuals in industrialized nations, the widespread adoption of electric lighting has dramatically affected the circadian organization of physiology and behavior. Although initially assumed to be innocuous, exposure to artificial light at night (ALAN) is associated with several disorders, including increased incidence of cancer, metabolic disorders, and mood disorders. Within this review, we present a brief overview of the molecular circadian clock system and the importance of maintaining fidelity to bright days and dark nights. We describe the interrelation between core clock genes and the cell cycle, as well as the contribution of clock genes to oncogenesis. Next, we review the clinical implications of disrupted circadian rhythms on cancer, followed by a section on the foundational science literature on the effects of light at night and cancer. Finally, we provide some strategies for mitigation of disrupted circadian rhythms to improve health.
Although much has been learned about circadian clocks and rhythms over the past few decades, translation of this foundational science underlying the temporal regulation of physiology and behavior to clinical applications has been slow. Indeed, acceptance of the modern study of circadian rhythms has been blunted because the phenomenology of cyclic changes had to counteract the 20th century dogma of homeostasis in the biological sciences and medicine. We are providing this review of clinical data to highlight the emerging awareness of circadian variation in efficacy of medications for physicians, clinicians, and pharmacists. We are suggesting that gold‐standard double‐blind clinical studies should be conducted to determine the best time of day for optimal effectiveness of medications; also, we suggest that time of day should be tracked and reported as an important biological variable in ongoing clinical studies hereafter. Furthermore, we emphasize that time of day is, and should be considered, a key biological variable in research design similar to sex. In common with biomedical research data that have been historically strongly skewed toward the male sex, most pharmaceutical data have been skewed toward morning dosing without strong evidence that this is the optimal time of efficacy.
Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social life around the clock. However, physiology and behavior that evolved in the context of 24 h solar days are frequently perturbed by exposure to artificial light at night. This is particularly salient in the context of circadian rhythms, the result of endogenous biological clocks with a rhythm of ~24 h. Circadian rhythms govern the temporal features of physiology and behavior, and are set to precisely 24 h primarily by exposure to light during the solar day, though other factors, such as the timing of meals, can also affect circadian rhythms. Circadian rhythms are significantly affected by night shift work because of exposure to nocturnal light, electronic devices, and shifts in the timing of meals. Night shift workers are at increased risk for metabolic disorder, as well as several types of cancer. Others who are exposed to artificial light at night or late mealtimes also show disrupted circadian rhythms and increased metabolic and cardiac disorders. It is imperative to understand how disrupted circadian rhythms alter metabolic function to develop strategies to mitigate their negative effects. In this review, we provide an introduction to circadian rhythms, physiological regulation of homeostasis by the suprachiasmatic nucleus (SCN), and SCN-mediated hormones that display circadian rhythms, including melatonin and glucocorticoids. Next, we discuss circadian-gated physiological processes including sleep and food intake, followed by types of disrupted circadian rhythms and how modern lighting disrupts molecular clock rhythms. Lastly, we identify how disruptions to hormones and metabolism can increase susceptibility to metabolic syndrome and risk for cardiovascular diseases, and discuss various strategies to mitigate the harmful consequences associated with disrupted circadian rhythms on human health.
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