Highlights

• Circadian disruption disrupts photoperiodic time measurement and seasonal adaptations.

•Light at night disrupts reproduction, immune function and metabolism, a crucial proxy for fitness.

https://doi.org/10.1016/j.yhbeh.2022.105150

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Source: https://www.eurekalert.org/news-releases/497871#

NEWS RELEASE 30-APR-2019

Disrupting normal circadian rhythms promotes tumor growth and suppresses the effects of a tumor-fighting drug, according to a new study publishing April 30 in the open-access journal PLOS Biology by Yool Lee, Amita Sehgal, and colleagues at the University of Pennsylvania. The results provide mechanistic support for “chronotherapy,” the delivery of cancer drugs timed to the endogenous circadian rhythm.

Circadian rhythms regulate many aspects of physiology from the organismic to the subcellular levels. Disruption of circadian rhythms, whether through jet travel, shift work, or sleep disturbances, is a known risk factor for several types of cancer. In animal models, hormonally induced circadian disruption promotes tumor growth, but the underlying mechanism or mechanisms have not been clear.

Read more at: https://www.eurekalert.org/news-releases/497871#

Citation: Lee Y, Lahens NF, Zhang S, Bedont J, Field JM, Sehgal A (2019) G1/S cell cycle regulators mediate effects of circadian dysregulation on tumor growth and provide targets for timed anticancer treatment. PLoS Biol 17(4): e3000228. https://doi.org/10.1371/journal.pbio.3000228

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Abstract

Particular working conditions and/or organization of working time may cause important sleep disturbances that have been proposed to be predictive of cognitive decline. In this regard, circadian rhythm misalignment induced by exposure to night work or long working hours would be responsible for cognitive impairment. Nevertheless, evidence supporting this correlation is limited and several issues still need to be elucidated. In this regard, we conducted a systematic review to evaluate the association between shift/night work and cognitive impairment and address its main determinants. Information provided by the reviewed studies suggested that night work might have serious immediate negative effects especially on cognitive domains related to attention, memory and response inhibition. Furthermore, cognitive performance would progressively worsen over consecutive night shifts or following exposure to very long work shifts. Otherwise, conflicting results emerged regarding the possible etiological role that night work chronic exposure would have on cognitive impairment. Therefore, circadian rhythm desynchronization, lack of sleep and fatigue resulting from night work may negatively impact worker’s cognitive efficiency. However, in light of the considerable methodological variability of the reviewed studies, we proposed to develop a standardized research and evaluation strategy in order to obtain a better and comprehensive understanding of this topic.

https://www.mdpi.com/1660-4601/18/12/6540

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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

The circadian clock is an endogenous timekeeper system that controls and optimizes biological processes, which are consistent with a master circadian clock and peripheral clocks and are controlled by various genes. Notably, the disruption of circadian clock genes has been identified to affect a wide range of ailments, including cancers. The cancer-immunity cycle is composed of seven major steps, namely cancer cell antigen release and presentation, priming and activation of effector immunity cells, trafficking, and infiltration of immunity to tumors, and elimination of cancer cells. Existing evidence indicates that the circadian clock functions as a gate that govern many aspects of the cancer-immunity cycle. In this review, we highlight the importance of the circadian clock during tumorigenesis, and discuss the potential role of the circadian clock in the cancer-immunity cycle. A comprehensive understanding of the regulatory function of the circadian clock in the cancer-immunity cycle holds promise in developing new strategies for the treatment of cancer.

https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00721-2

Excerpt

Disruption of the circadian clock contributes to cancer

Over the past years, studies have shown that disruption of the circadian rhythm contributes to the incidence and development of various cancer [49, 50]. Previous studies have revealed that shift work is implicated in tumorigenesis [51, 52]. Women who work at night instead of days exhibit an approximately 10% increased risk of breast cancer [53,54,55].

Of note, the disruption of life cycle oscillation causes the increase of spontaneous cancer in chronic jet-lag mouse model. For example, Minami et al. discussed that chronic jet-lag mice showed the short lifespan, splenomegaly, and the accelerated development of liver cancer [57]. In addition, the chrono-disruption of the circadian clock is crucial in metabolic and immunologic changes and is implicated in non-alcoholic fatty liver disease/nonalcoholic steato-hepatitis/hepatocellular cancer [58].

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Abstract

The circadian clock exerts an important role in systemic homeostasis as it acts a keeper of time for the organism. The synchrony between the daily challenges imposed by the environment needs to be aligned with biological processes and with the internal circadian clock. In this review, it is provided an in-depth view of the molecular functioning of the circadian molecular clock, how this system is organized, and how central and peripheral clocks communicate with each other. In this sense, we provide an overview of the neuro-hormonal factors controlled by the central clock and how they affect peripheral tissues. We also evaluate signals released by peripheral organs and their effects in the central clock and other brain areas. Additionally, we evaluate a possible communication between peripheral tissues as a novel layer of circadian organization by reviewing recent studies in the literature. In the last section, we analyze how the circadian clock can modulate intracellular and tissue-dependent processes of metabolic organs. Taken altogether, the goal of this review is to provide a systemic and integrative view of the molecular clock function and organization with an emphasis in metabolic tissues.

Conclusions

The circadian clock system is a complex and pervasive network that directly or indirectly controls a significant portion of all biological processes. Its role as a systemic regulator is seen in experimental models of gene silencing or knockout. Advancements in tissue-specific clock gene modulation has been important for a better understanding of tissue clock gene organization at both cellular as well as systemic levels. In addition to its molecular basis, the organizational aspects of the circadian clock network have received increased attention over the last years. Understanding how this biological timing machinery works at all levels of organization will be important to fully assess the consequences of circadian rhythm disruption by modern lifestyles and devise ways to prevent chronodisruption and treat associated diseases and conditions.

https://link.springer.com/article/10.1007/s00018-021-03800-2

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Abstract

Despite the strong evidence on circadian rhythm disruption in shift workers and consequent increased vulnerability for infection, longitudinal association between shift work and COVID-19 infection is unexplored. In this study, data from UK Biobank participants who were tested for COVID-19 infection (16 March to 7 September 2020) were used to explore the link between shift work and COVID-19 infection. Using the baseline occupational information, participants were categorised as non-shift workers, day shift workers, mixed shift workers and night shift workers. Multivariable regression models were used to assess the association between shift work and COVID-19 infection. Among the 18,221 participants (9.4% positive cases), 11.2% were health workers, and 16.4% were involved in shift-work-based jobs. Ethnic minorities (18%) and people in night-shift-based jobs (18.1%) had a significantly higher prevalence of COVID-19 infection than others. Adjusted logistics regression model suggest that, compared with their counterparts, people employed in a night-shift-based job were 1.85-fold (95% CI: 1.42-2.41) more likely to have COVID-19 infection. Sensitivity analysis focusing on people working in a non-healthcare setting suggests that people in shift-work-based jobs had 1.81-fold (95% CI: 1.04%-3.18%) higher odds of COVID-19 infection than their counterparts. Shift workers, particularly night shift workers, irrespective of their occupational group, seem to be at high risk of COVID-19 infection. If similar results are obtained from other studies, then it would mandate to revisit the criteria for defining high-risk groups for COVID-19 and implementing appropriate interventions to protect people in shift-based jobs.

5 CONCLUSION

The findings of this paper provide preliminary but strong evidence for the role of shift work in COVID‐19 infection. Thus, when we are considering risk factors for COVID‐19 and/or vulnerability for the condition, which may prompt testing, shift work might be one of the additional factors to be considered for timely intervention and management of at‐risk patients. This study is based on the most recent data from the UK Biobank and over 35% of the study participants were tested more than once; nonetheless, considering that the pandemic is still ongoing, many of the individuals who were negative at the time of the data analysis might not still be negative. The change in COVID infection status might affect the strength of the association between shift work and COVID‐19 infection. Therefore, as more data become available, an addendum to the current work will be useful in the current estimation of the impact of shift work on COVID‐19 infection risk.

https://onlinelibrary.wiley.com/doi/10.1111/jsr.13326

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