This editorial refers to ‘Outdoor light at night and risk of coronary heart disease among older adults: a prospective cohort study’^†, by S. Sun et al., on page 822

Environmental triggers of the global burden of disease and deaths

The aim of exposome research is to characterize the impact of all environmental exposures during our entire life span on the biochemical systems in our body and their associated (mostly adverse) health effects.¹ The need for exposome research is emphasized by health side effects caused by ambient chemical pollution (from soil, water, and air) leading to up to 13 million premature deaths worldwide, with a major part representing non-communicable diseases.² However, these numbers do not take into account the impact of additional environmental stressors contributing significantly to the global burden of disease such as light exposure, mental stress, and the temperature.³ The leading role of air pollution [e.g. fine particulate matter, particles with a diameter <2.5 µm (PM_2.5)] as an environmental health risk factor is well established, especially for causing cardiovascular disease including ischaemic heart disease and stroke, and by increasing mortality.^4,5 There is also a growing body of evidence showing that noise, in particular transportation noise, represents an important environmental health risk factor, mainly by increasing the risk of cardiovascular, metabolic, and neuropsychological disease and thereby causing ∼1.6 million disability-adjusted life years in the Western European region.⁶ The adverse health effects of nocturnal light pollution are not very well characterized so far, highlighting the novelty of the work by Sun et al. published in this issue of the European Heart Journal.⁷ Within the next sections we will provide a short overview of the importance of light exposure at night as a potential health risk factor and try to elucidate its major mechanism of action. We will also critically evaluate the major messages of the current work by Sun et al. and discuss their societal impact.

Read more at: https://academic.oup.com/eurheartj/article/42/8/831/5998262

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Video Abstract:

Introduction

The circadian circuit, a roughly 24 h molecular feedback loop, or clock, is conserved from bacteria to animals and allows for enhanced organismal survival by facilitating the anticipation of the day/night cycle. With circadian regulation reportedly impacting as high as 80% of protein coding genes in higher eukaryotes, the protein-based circadian clock broadly regulates physiology and behavior. Due to the extensive interconnection between the clock and other cellular systems, chronic disruption of these molecular rhythms leads to a decrease in organismal fitness as well as an increase of disease rates in humans. Importantly, recent research has demonstrated that proteins comprising the circadian clock network display a significant amount of intrinsic disorder.

Background, Extract

With this sizeable amount of gene regulation, and by extension physiology, it is no surprise that the disruption of circadian rhythms has been noted to lead to decreased physiological fitness [3, 26]. Chronic circadian disruption has been linked with many disease states, including a higher risk of obesity, heart disease, diabetes, depression, and cancer [27,28,29,30,31]. Furthermore, genes under the control of the circadian clock show a strong correlation with disease-associated genes and out of the top 100 selling drugs in the US, 56 target a gene under circadian regulation (including the top 7) [32]. With 20% of the working population subject to “shift work” and the widespread use of digital screens and blue-light-emitting devices, circadian disruption is a growing cause of preventable disease [33, 34].

Conversely, methods of circadian intervention and treatment have been developed, including the application of light-based therapy for dementia-related pathologies. For example, Alzheimer’s disease commonly results in disturbances to circadian rhythms, leading to increased deposition of the plaques that exacerbate Alzheimer’s disease pathology. This in turn leads to further dysregulation of the circadian clock, thus creating a positive feedback loop with negative effects on the pathology and progression of Alzheimer’s disease. As a treatment modality, optimized circadian entrainment lighting for patients with Alzheimer’s disease has been implemented in assisted living facilities and has been shown to improve behavior, sleep, and mood [35]. In summary, the circadian system has been shown to play an essential role in organismal health and physiology, though many questions still remain detailing its extensive reaches into the cell.

Conclusions

IDPs have been suggested to serve important roles in finely tuning the circadian regulatory circuit through post-transcriptional regulation, multiple interacting partners, and many other mechanisms. We have discussed examples of disorder in the clock and how they underlie the mechanisms for several of the phenomena in the circadian system from timing, to the regulation of output, to providing the capacity for the clock to respond to cellular conditions. Considering the complexity and deep reaches of the molecular circadian circuit, disorder presents an essential and inherent mechanism of biological control, supported by the conservation of protein disorder in clocks from lower to higher eukaryotes.

https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00658-y

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