Impact of Circadian Disruption on Cardiovascular Function and Disease

Chellappa, Sarah Laxhmi; Vujović, Nina; Williams, Jonathan S.; Scheer, Frank A.J.L.

doi:10.1016/j.tem.2019.07.008

Cited by 179 publications

(121 citation statements)

References 90 publications

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“…Our comprehensive transcriptome, proteome, and phosphoproteome analyses might provide a starting point to identify and validate markers for such a stratification in humans. Lastly, our data indicate that training is not only not a strong Zeitgeber in a healthy mouse muscle, but, if chronically performed at the wrong time of the day, might lead to perturbations of the muscle clock which resemble perturbations of other peripheral clocks in pathological states and in aging, characterized by a general dampening of oscillation amplitudes (Chellappa et al, 2019;Rijo-Ferreira and Takahashi, 2019). Our experiments, however, will not allow any conclusions about a potential therapeutic effect of timed training (chronoexercise) on muscle and other peripheral clocks in pathologies that are linked to abnormal circadian rhythmicity (Cederroth et al, 2019).…”

Section: Discussionmentioning

confidence: 79%

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Maier

Delezie

Westermark

et al. 2020

Preprint

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Timed physical activity might potentiate the health benefits of training. The underlying signaling events triggered by exercise at different times of the day are, however, poorly understood. Here, we found that time-dependent variations in maximal treadmill exercise capacity of naive mice were associated with energy stores, mostly hepatic glycogen levels. Importantly, running at different times of the day resulted in a vastly different activation of signaling pathways, e.g., related to stress response, vesicular trafficking, repair, and regeneration. Second, voluntary wheel running at the opposite phase of the dark, feeding period surprisingly revealed minimal Zeitgeber (i.e., synchronizing) activity of training. This integrated study provides important insights into the circadian regulation of endurance performance and the control of the circadian clock by exercise. These results are of high importance to understand circadian aspects of training design in athletes and the application of chrono-exercise-based interventions in patients.

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Section: Discussionmentioning

confidence: 79%

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Maier

Delezie

Westermark

et al. 2020

Preprint

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“…include cardiovascular and lung disorders, diabetes, and cancer. 65 Many of the specific medical conditions that are included within these groups of disorders are linked to an elevation in gut dysbiosis/ permeability, 66,67 mitochondrial dysfunction, 68 and circadian dysregulation, 69,70 with melatonin showing utility in their management. 71,72 Ageing, the main risk factor for death from influenza and covid-19, is highly associated with these pathophysiological changes, [73][74][75][76] with melatonin, partly via sirtuin induction as well as circadian and mitochondria regulation, attenuating ageing-associated processes.…”

Section: Preexisting Medical Conditionsmentioning

confidence: 99%

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Anderson¹,

Reíter

2020

Reviews in Medical Virology

171

166

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There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus-and cytokinestorm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.

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“…Among the consequences of staying indoors during the forced lockdown period, disruption of circadian rhythmicity, in particular, of the sleep/wake cycle is highly frequent, and age-associated circadian misalignment prevails [6,7]. Dysregulation of circadian timing systems is thought to be involved in several medical and mental conditions in aged individuals including cardiovascular and neurodegenerative diseases [8,9]. Herein, we briefly discuss how chronotherapy may reverse the detrimental circadian condition of the elderly in the COVID-19 pandemic.…”

Section: Introductionmentioning

confidence: 99%

Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration

et al. 2020

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The association of age with a higher vulnerability to COVID-19 infection is a subject of major importance. Several factors, including higher stress due to social isolation, diminished melatonin levels with age, and higher exposure of individuals to light at the evening, which reduces melatonin levels and disrupts circadian rhythmicity are relevant for maintaining the circadian health in aged individuals. Properly administered, chronotherapy restores the optimal circadian pattern of the sleep-wake cycle in the elderly. It involves adequate sleep hygiene, timed light exposure, and the use of a chronobiotic medication like melatonin, which affects the output phase of circadian rhythms thus controlling the biological clock. Besides, the therapeutic potential of melatonin as an agent to counteract the consequences of COVID-19 infections has been advocated due to its wide-ranging effects as an antioxidant, anti-inflammatory, and as an immunomodulatory agent, as well as to a possible antiviral action. This article discusses how chronotherapy may reverse the detrimental circadian condition of the elderly in the COVID-19 pandemic.

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Impact of Circadian Disruption on Cardiovascular Function and Disease

Cited by 179 publications

References 90 publications

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration

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