Abstract Sleep/wake timing shifts later in young humans during the second decade of life. In this review we describe sleep/wake patterns, changes in these patterns across adolescence, and evidence ...for the role of environmental, psychosocial, and biological factors underlying these changes. A two-process model incorporating circadian (Process C) and sleep/wake homeostatic (Process S) components is outlined. This model may help us to understand how developmental changes translate to shifted sleep/wake patterns. Delayed sleep phase syndrome (DSPS), which has a typical onset during the second decade of life, may be an extreme manifestation of homeostatic and circadian changes in adolescence. We describe symptoms, prevalence, and possible etiology of DSPS, as well as treatment approaches in adolescents.
Circadian rhythms are 24-h patterns regulating behavior, organs, and cells in living organisms. These rhythms align biological functions with regular and predictable environmental patterns to ...optimize function and health. Disruption of these rhythms can be detrimental resulting in metabolic syndrome, cancer, or cardiovascular disease, just to name a few. It is now becoming clear that the intestinal microbiome is also regulated by circadian rhythms via intrinsic circadian clocks as well as via the host organism. Microbiota rhythms are regulated by diet and time of feeding which can alter both microbial community structure and metabolic activity which can significantly impact host immune and metabolic function. In this review, we will cover how host circadian rhythms are generated and maintained, how host circadian rhythms can be disrupted, as well as the consequences of circadian rhythm disruption. We will further highlight the newly emerging literature indicating the importance of circadian rhythms of the intestinal microbiota.
Humans, like all mammals, partition their daily behaviour into activity (wakefulness) and rest (sleep) phases that differ largely in their metabolic requirements. The circadian clock evolved as an ...autonomous timekeeping system that aligns behavioural patterns with the solar day and supports the body functions by anticipating and coordinating the required metabolic programmes. The key component of this synchronization is a master clock in the brain, which responds to light-darkness cues from the environment. However, to achieve circadian control of the entire organism, each cell of the body is equipped with its own circadian oscillator that is controlled by the master clock and confers rhythmicity to individual cells and organs through the control of rate-limiting steps of metabolic programmes. Importantly, metabolic regulation is not a mere output function of the circadian system, but nutrient, energy and redox levels signal back to cellular clocks in order to reinforce circadian rhythmicity and to adapt physiology to temporal tissue-specific needs. Thus, multiple systemic and molecular mechanisms exist that connect the circadian clock with metabolism at all levels, from cellular organelles to the whole organism, and deregulation of this circadian-metabolic crosstalk can lead to various pathologies.
Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic ...syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers.
Circadian rhythms govern a large array of physiological and metabolic functions. Perturbations of the daily cycle have been linked to elevated risk of developing cancer as well as poor prognosis in ...patients with cancer. Also, expression of core clock genes or proteins is remarkably attenuated particularly in tumours of a higher stage or that are more aggressive, possibly linking the circadian clock to cellular differentiation. Emerging evidence indicates that metabolic control by the circadian clock underpins specific hallmarks of cancer metabolism. Indeed, to support cell proliferation and biomass production, the clock may direct metabolic processes of cancer cells in concert with non-clock transcription factors to control how nutrients and metabolites are utilized in a time-specific manner. We hypothesize that the metabolic switch between differentiation or stemness of cancer may be coupled to the molecular clockwork. Moreover, circadian rhythms of host organisms appear to dictate tumour growth and proliferation. This Review outlines recent discoveries of the interplay between circadian rhythms, proliferative metabolism and cancer, highlighting potential opportunities in the development of future therapeutic strategies.
Circadian rhythms and pain Bumgarner, Jacob R.; Walker, William H.; Nelson, Randy J.
Neuroscience and biobehavioral reviews,
10/2021, Letnik:
129
Journal Article
Recenzirano
Odprti dostop
The goal of this review is to provide a perspective on the nature and importance of the relationship between the circadian and pain systems. We provide: 1) An overview of the circadian and pain ...systems, 2) a review of direct and correlative evidence that demonstrates diurnal and circadian rhythms within the pain system; 3) a perspective highlighting the need to consider the role of a proposed feedback loop of circadian rhythm disruption and maladaptive pain; 4) a perspective on the nature of the relationship between circadian rhythms and pain. In summary, we propose that there is no single locus responsible for producing the circadian rhythms of the pain system. Instead, circadian rhythms of pain are a complex result of the distributed rhythms present throughout the pain system, especially those of the descending pain modulatory system, and the rhythms of the systems with which it interacts, including the opioid, endocrine, and immune systems.
The blood vessels in the central nervous system (CNS) have a series of unique properties, termed the blood-brain barrier (BBB), which stringently regulate the entry of molecules into the brain, thus ...maintaining proper brain homeostasis. We sought to understand whether neuronal activity could regulate BBB properties. Using both chemogenetics and a volitional behavior paradigm, we identified a core set of brain endothelial genes whose expression is regulated by neuronal activity. In particular, neuronal activity regulates BBB efflux transporter expression and function, which is critical for excluding many small lipophilic molecules from the brain parenchyma. Furthermore, we found that neuronal activity regulates the expression of circadian clock genes within brain endothelial cells, which in turn mediate the activity-dependent control of BBB efflux transport. These results have important clinical implications for CNS drug delivery and clearance of CNS waste products, including Aβ, and for understanding how neuronal activity can modulate diurnal processes.
•Neuronal activity robustly regulates gene expression in brain endothelial cells•Neuronal activity regulates BBB efflux transport and endothelial circadian genes•Efflux transport rhythmically correlates with neuronal activity across the day•Neuronal activity regulates BBB efflux via modulation of endothelial circadian genes
The authors demonstrate that brain endothelial gene expression and blood-brain barrier efflux exhibit plasticity in response to neuronal activity. This has implications for how the blood-brain barrier regulates the composition of endogenous and exogenous molecules in the central nervous system in relation to circadian time and neuronal activity. This also suggests that neuronal activity can extrinsically modulate otherwise cell-intrinsic oscillatory processes.
Cellular life emerged ∼3.7 billion years ago. With scant exception, terrestrial organisms have evolved under predictable daily cycles owing to the Earth's rotation. The advantage conferred on ...organisms that anticipate such environmental cycles has driven the evolution of endogenous circadian rhythms that tune internal physiology to external conditions. The molecular phylogeny of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins are not conserved across the domains of life: Bacteria, Archaea and Eukaryota. Here we show that oxidation-reduction cycles of peroxiredoxin proteins constitute a universal marker for circadian rhythms in all domains of life, by characterizing their oscillations in a variety of model organisms. Furthermore, we explore the interconnectivity between these metabolic cycles and transcription-translation feedback loops of the clockwork in each system. Our results suggest an intimate co-evolution of cellular timekeeping with redox homeostatic mechanisms after the Great Oxidation Event ∼2.5 billion years ago.
The circadian system of the cyanobacterium
PCC 7942 relies on a three-protein nanomachine (KaiA, KaiB, and KaiC) that undergoes an oscillatory phosphorylation cycle with a period of ~24 h. This core ...oscillator can be reconstituted in vitro and is used to study the molecular mechanisms of circadian timekeeping and entrainment. Previous studies showed that two key metabolic changes that occur in cells during the transition into darkness, changes in the ATP/ADP ratio and redox status of the quinone pool, are cues that entrain the circadian clock. By changing the ATP/ADP ratio or adding oxidized quinone, one can shift the phase of the phosphorylation cycle of the core oscillator in vitro. However, the in vitro oscillator cannot explain gene expression patterns because the simple mixture lacks the output components that connect the clock to genes. Recently, a high-throughput in vitro system termed the in vitro clock (IVC) that contains both the core oscillator and the output components was developed. Here, we used IVC reactions and performed massively parallel experiments to study entrainment, the synchronization of the clock with the environment, in the presence of output components. Our results indicate that the IVC better explains the in vivo clock-resetting phenotypes of wild-type and mutant strains and that the output components are deeply engaged with the core oscillator, affecting the way input signals entrain the core pacemaker. These findings blur the line between input and output pathways and support our previous demonstration that key output components are fundamental parts of the clock.
Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light—stimuli at extreme ends of the circadian system’s dose–response ...curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose–response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10–2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.
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