The publisher’s final edited version of this article is available at Science

Abstract

Circadian clocks temporally coordinate physiology and align it with geophysical time, enabling diverse lifeforms to anticipate daily environmental cycles. In complex organisms, clock function originates from the molecular oscillator within each cell and builds upwards anatomically into an organism-wide system. Recent advances have transformed our understanding of how clocks are connected to achieve coherence across tissues. Circadian misalignment, often imposed in modern society, disrupts coordination among clocks and has been linked to diseases from metabolic syndrome to cancer. Thus, uncovering the physiological circuits whereby biological clocks achieve coherence will inform on both challenges and opportunities in human health.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123919/

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Highlights

Although circadian rhythm disruption (CRD) was typically considered to be a risk for chronic diseases solely for shift workers (∼20% of workforce), new epidemiological data suggest more than 80% of the population may be living a shift work lifestyle and thus are at elevated risk for chronic diseases.

Acute CRD compromises health with temporary physical challenges and may be a trigger for underlying latent diseases. Chronic CRD raises the risk for cancer along with a range of diseases affecting the central nervous system, immune and reproductive systems, metabolic organs, endocrine functions, and cardiovascular health.

Recent progress in understanding the molecular mechanisms of circadian timing and diurnal rhythms of tissue-specific gene products has generated testable hypotheses for how the circadian timing system optimizes health and, conversely, how circadian disruption leads to diseases.

Leveraging circadian rhythms to prevent, manage, and treat diseases involves three major strategies: optimizing the circadian lifestyle (‘training the clock’), optimizing timing of therapies (‘clocking the drugs’), and targeting specific circadian clock components (‘drugging the clock’).

Daily rhythms in behavior, physiology, and metabolism are an integral part of homeostasis. These rhythms emerge from interactions between endogenous circadian clocks and ambient light-dark cycles, sleep-activity cycles, and eating-fasting cycles. Nearly the entire primate genome shows daily rhythms in expression in tissue- and locus-specific manners. These molecular rhythms modulate several key aspects of cellular and tissue function with profound implications in public health, disease prevention, and disease management. In modern societies light at night disrupts circadian rhythms, leading to further disruption of sleep-activity and eating-fasting cycles. While acute circadian disruption may cause transient discomfort or exacerbate chronic diseases, chronic circadian disruption can enhance risks for numerous diseases. The molecular understanding of circadian rhythms is opening new therapeutic frontiers placing the circadian clock in a central role. Here, we review recent advancements on how to enhance our circadian clock through behavioral interventions, timing of drug administration, and pharmacological targeting of circadian clock components that are already providing new preventive and therapeutic strategies for several diseases, including metabolic syndrome and cancer.

https://www.sciencedirect.com/science/article/abs/pii/S0165614718301196

© 2018 Elsevier Ltd. All rights reserved.

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Abstract

Background

Understanding factors impacting deaths from COVID‐19 is of the highest priority. Seasonal variation in environmental meteorological conditions affects the incidence of many infectious diseases and may also affect COVID‐19. Ultraviolet A (UVA) radiation induces release of cutaneous photolabile nitric oxide (NO) impacting the cardiovascular system and metabolic syndrome, both COVID‐19 risk factors. NO also inhibits the replication of SARS‐CoV2.

Objectives

To investigate the relationship between ambient UVA radiation and COVID‐19 deaths.

Methods

COVID‐19 deaths at the county level, across the USA, were modelled in a Zero Inflated Negative Binomial model with a random effect for States adjusting for confounding by demographic, socioeconomic and long‐term environmental variables. Only areas where UVB was too low to be inducing significant cutaneous vitamin D3 synthesis were modelled. We used satellite‐derived estimates of UVA, UVB and temperature and relative humidity. Replication models were undertaken using comparable data for England and Italy.

Results

The Mortality Risk Ratio (MRR), in the USA, falls by 29% (40% ‐15% (95% CI)) per 100 (KJ/m²) increase in mean daily UVA. We replicate this in independent studies in Italy and England and estimate a pooled decline in MRR of 32% (48%‐12%) per 100 KJ/m² across the three studies.

Conclusions

Our analysis suggests that higher ambient UVA exposure is associated with lower COVID‐19 specific mortality. Further research on the mechanism may indicate novel treatments. Optimised UVA exposure may have population health benefits.

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Abstract

Emerging evidence has identified sleep as a significant, but modifiable, risk factor for metabolic syndrome, diabetes, and obesity. Leptin, an adipocyte-derived peptide and a regulator of food intake and energy expenditure, has been shown to be associated with a short sleep duration in the pathophysiology of obesity and consequently type 2 diabetes. This review focuses on the current evidence indicating the effects of a short sleep duration on the regulation of leptin concentration in association with obesity and diabetes mellitus. In summary, the evidence suggests that sleep deprivation, by affecting leptin regulation, may lead to obesity and consequently development of type 2 diabetes through increased appetite and food intake. However, findings on the role of leptin in diabetes due to sleep deprivation are contradictory, and further studies with larger sample sizes are needed to confirm previous findings.

https://pubmed.ncbi.nlm.nih.gov/33756469/

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Abstract

“Life is an instantaneous encounter of circulating matter and flowing energy” (Jean Giaja, Serbian physiologist), is one of the most elegant definitions not only of life but the relationship of redox biology and metabolism. Their evolutionary liaison has created inseparable yet dynamic homeostasis in health, which, when disrupted, leads to disease. This interconnection is even more pertinent today, in an era of increasing metabolic diseases of epidemic proportions such as obesity, metabolic syndrome, and diabetes. Despite great advances in understanding the molecular mechanisms of redox and metabolic regulation, we face significant challenges in preventing, diagnosing, and treating metabolic diseases. The etiological association and temporal overlap of these syndromes present significant challenges for the discrimination of appropriate clinical biomarkers for diagnosis, treatment, and outcome prediction. These multifactorial, multiorgan metabolic syndromes with complex etiopathogenic mechanisms are accompanied by disturbed redox equilibrium in target tissues and circulation. Free radicals and reactive species are considered both a causal factor and a consequence of disease status. Thus, determining the subtypes and levels of free radicals and reactive species, oxidatively damaged biomolecules (lipids, proteins, and nucleic acids) and antioxidant defense components as well as redox-sensitive transcription factors and fluxes of redox-dependent metabolic pathways will help define existing and establish novel redox biomarkers for stratifying metabolic diseases. This review aims to discuss diverse redox/metabolic aspects in obesity, metabolic syndrome, and diabetes, with the imperative to help establish a platform for emerging and future redox-metabolic biomarkers research in precision medicine. Future research warrants detailed investigations into the status of redox biomarkers in healthy subjects and patients, including the use of emerging ‘omic’ profiling technologies (e.g., redox proteomes, lipidomes, metabolomes, and transcriptomes), taking into account the influence of lifestyle (diet, physical activity, sleep, work patterns) as well as circadian ~24h fluctuations in circulatory factors and metabolites.

https://www.sciencedirect.com/science/article/pii/S2213231721000355#undfig1

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Abstract

The metabolic syndrome is prevalent in developed nations and accounts for the largest burden of non-communicable diseases worldwide. The metabolic syndrome has direct effects on health and increases the risk of developing cancer. Lifestyle factors that are known to promote the metabolic syndrome generally cause pro-inflammatory alterations in microbiota communities in the intestine. Indeed, alterations to the structure and function of intestinal microbiota are sufficient to promote the metabolic syndrome, inflammation and cancer. Among the lifestyle factors that are associated with the metabolic syndrome, disruption of the circadian system, known as circadian dysrhythmia, is increasingly common. Disruption of the circadian system can alter microbiome communities and can perturb host metabolism, energy homeostasis and inflammatory pathways, which leads to the metabolic syndrome. This Perspective discusses the role of intestinal microbiota and microbial metabolites in mediating the effects of disruption of circadian rhythms on human health.

https://www.nature.com/articles/s41574-020-00427-4

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Abstract

Day and night cycles are the most important cue for the central clock of human beings, and they are also important for the gut clock. The aim of the study is to determine the differences in the gut microbiota of rotational shift workers when working the day versus night shift. Fecal samples and other data were collected from 10 volunteer male security officers after 4 weeks of day shift work (07:00-15:00 h) and also after 2 weeks of night shift work (23:00-07:00 h). In total, 20 stool samples were collected for analysis of gut microbiota (10 subjects x 2 work shifts) and stored at -80°C until analysis by 16 S rRNA sequencing. The relative abundances of Bacteroidetes were reduced and those of Actinobacteria and Firmicutes increased when working the night compared to day shift. Faecalibacterium abundance was found to be a biomarker of the day shift work. Dorea longicatena and Dorea formicigenerans were significantly more abundant in individuals when working the night shift. Rotational day and night shift work causes circadian rhythm disturbance with an associated alteration in the abundances of gut microbiota, leading to the concern that such induced alteration of gut microbiota may at least partially contribute to an increased risk of future metabolic syndrome and gastrointestinal pathology.

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