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Circadian rhythms are fundamental biological processes that recur approximately every 24 h, with the sleep-wake cycle or circadian behavior being a well-known example. In the field of chronobiology, mice serve as valuable model animals for studying mammalian circadian rhythms due to their genetic similarity to humans and the availability of various genetic tools for manipulation. Monitoring locomotor activity in mice provides valuable insights into the impact of various conditions or disturbances on circadian behavior. In this review, we summarized the effects of disturbance of biological rhythms on circadian behavior in mice. External factors, especially light exert a significant impact on circadian behavior. Additionally, feeding timing, food composition, ambient temperature, and physical exercise contribute to variations in the behavior of the mouse. Internal factors, including gender, age, genetic background, and clock gene mutation or deletion, are effective as well. Understanding the effects of circadian disturbances on murine behavior is essential for gaining insights into the underlying mechanisms of circadian regulation and developing potential therapeutic interventions for circadian-related disorders in humans., (© 2024 Federation of American Societies for Experimental Biology.)

Glucocorticoid (GC) hormones are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being assessed. In the setting of extreme perturbations in cortisol levels ie, markedly low or high levels, symptoms and signs of GC dysfunction may be overt. However, when disturbances in cortisol GC status values are less extreme, such as when assessing optimization of a GC replacement regimen, signs and symptoms can be more subtle or nonspecific. Current tools for assessing GC status are best suited to identifying profound disturbances but may lack sensitivity for confirming optimal GC status. Moreover, single cortisol values do not necessarily reflect an individual's GC status, as they are subject to inter- and intraindividual variation and do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11beta-hydroxysteroid dehydrogenase activity, as well as GC receptor sensitivity. In the present review, we evaluate possible alternative methods for the assessment of GC status that do not solely rely on the measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, micro RNA, gene expression, and epigenetic and other novel biomarkers such as growth differentiating factor 15 and osteocalcin, which could in the future aid in the objective classification of GC status., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Anxiety disorders significantly impair the quality of life (QOL). Studies on the effect of sleep duration, chronotype, and social jet lag on anxiety disorders are limited. This study aimed to elucidate the contributions of sleep duration, chronotype, and social jet lag to the prevalence and severity of anxiety disorders in Koreans., Methods: This study used data of 9,874 Korean adults from the Korea National Health and Nutrition Examination Survey 2021-2022. Anxiety was assessed using the Generalized Anxiety Disorder-7 scale, and health-related QOL was measured using the Health-Related Quality of Life Instrument with 8-Items. Complex sample logistic regression models were used to evaluate the associations between sleep duration, chronotype, and social jet lag and anxiety disorders, with analyses stratified by sex., Results: Sleep duration of <6 h, evening chronotype, and social jet lag of >2 h were significantly associated with a high prevalence of anxiety disorders in women; however, in men, only sleep duration of <6 h was associated with anxiety disorders. Sleep duration of <6 h and evening chronotype were associated with low QOL in women but not in men., Conclusion: This study highlights the importance of adequate sleep and circadian alignment for mental health, particularly in women. Public health initiatives should focus on promoting healthy sleep habits to improve mental health and QOL. Further research is required to understand the causal pathways and sex-specific mechanisms underlying these associations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jung, Lee. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The hypothalamus senses the appetite-regulating hormones and also coordinates the metabolic function in alignment with the circadian rhythm. This alignment is essential to maintain the physiological conditions that prevent clinically important comorbidities, such as obesity or type-2 diabetes. However, a complete model of the hypothalamus that relates food intake with circadian rhythms and appetite hormones has not yet been developed. In this work, we present a computational model that accurately allows interpreting neural activity in terms of hormone regulation and sleep-wake cycles. We used a conductance-based model, which consists of a system of four differential equations that considers the ionotropic and metabotropic receptors, and the input currents from homeostatic hormones. We proposed a logistic function that fits available experimental data of insulin hormone concentration and added it into a short-term ghrelin model that served as an input to our dynamical system. Our results show a double oscillatory system, one synchronized by light-regulated sleep-wake cycles and the other by food-regulated feeding-fasting cycles. We have also found that meal timing frequency is highly relevant for the regulation of the hypothalamus neurons. We therefore present a mathematical model to explore the plausible link between the circadian rhythm and the endogenous food clock., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Melatonin is a hormone known as an endogenous temporal marker signaling the dark phase of the day. Although the eyes seem to be the main site of melatonin production in amphibians, little information is available about the natural variation in ocular melatonin levels and its modulation following immune stimulation. We investigated the daily variation of plasma and ocular melatonin levels in bullfrogs (Lithobates catesbeianus) and their modulation following an immune stimulation with lipopolysaccharide (LPS) in yellow cururu toads (Rhinella icterica). For the daily variation, bullfrogs were bled and then euthanized for eye collection every 3 h over 24 h to determine plasma and ocular melatonin levels. We found a positive correlation between ocular and plasma melatonin levels, with maximum values at night (22 h) for both plasma and the eyes. For immune stimulation, yellow cururu toads received an intraperitoneal injection of LPS or saline solution during the day (10 h) or at night (22 h). Two hours after injection, toads were bled and euthanized for eye collection to obtain plasma and ocular melatonin levels. In addition, the liver and bone marrow were collected to investigate local melatonin modulation. Our results demonstrate that retinal light-controlled rhythmic melatonin production is suppressed while liver and bone marrow melatonin levels increase during the inflammatory assemblage in anurans. Interestingly, the LPS injection decreased only ocular melatonin levels, reinforcing the central role of the eyes (i.e., retina) as an essential organ of melatonin production, and a similar role to the pineal gland during the inflammatory response in amphibians. Together, these results point to a possible immune-pineal-ocular axis in amphibians, yet to be fully described in this group., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

New work by Mark Wu's group 1 in this issue of Neuron indicates that a neural population within the lateral amygdala, defined by the expression of mWAKE, functions as a crucial circadian oscillator to drive circadian rhythms in anxiety and touch sensitivity., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The chronotype of individuals has been found to be predictive of depression risk and associated with the severity of depression. However, since depression is a phenotypically heterogeneous disease, it seems improbable that chronotype plays a role in every instance of depression. This study investigates the association between the two, while considering possible symptom-specificity and non-linearity of the relationship, utilizing a large sample from the National Health and Nutrition Examination Survey (N = 5217; 54% female; Age: M = 52.65, SD = 18.76). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and chronotype was determined by calculating sleep midpoints. Further, we also explored the potential mediating role of systemic inflammation, measured by C-reactive protein (CRP) levels, in the chronotype-depression link. The findings substantiate previous research indicating late chronotypes to be associated with higher PHQ-9 sum scores, with a minimum in PHQ-9 at a sleep midpoint of 02:49. The study further differentiates between individual depression symptoms, uncovering varying patterns of association with chronotype. No significant effect of chronotype on levels of CRP was found, suggesting that the link between chronotype and depression symptoms may not be directly mediated and appears to be stable and independent from systemic inflammation. The study highlights the non-linear and symptom-specific nature of the chronotype-depression connection and suggests the need for further, longitudinal studies to elucidate causal mechanisms and potential mediators., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Circadian rhythms are generated by the master pacemaker suprachiasmatic nucleus (SCN) in concert with local clocks throughout the body. Although many brain regions exhibit cycling clock gene expression, the identity of a discrete extra-SCN brain oscillator that produces rhythmic behavior has remained elusive. Here, we show that an extra-SCN oscillator in the lateral amygdala (LA) is defined by expression of the clock-output molecule mWAKE/ANKFN1. mWAKE is enriched in the anterior/dorsal LA (adLA), and, strikingly, selective disruption of clock function or excitatory signaling in adLA mWAKE neurons abolishes Period2 (PER2) rhythms throughout the LA. mWAKE levels rise at night and promote rhythmic excitability of adLA mWAKE neurons by upregulating Ca 2+ -activated K + channel activity specifically at night. adLA mWAKE neurons coordinate rhythmic sensory perception and anxiety in a clock-dependent and WAKE-dependent manner. Together, these data reveal the cellular identity of an extra-SCN brain oscillator and suggest a multi-level hierarchical system organizing molecular and behavioral rhythms., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at 4 times-of-day (zeitgeber times 1, 7, 13, 19). Significantly, though both muscles demonstrated circadian-related changes in gene expression, there were no differences between the 4 time points in intrinsic contractile function, endurance, and contraction-stimulated glucose uptake, regardless of sex. Overall, these results suggest that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Physiological Society.)

Bile acids are trans-genomic molecules arising from the concerted metabolism of the human host and the intestinal microbiota and are important for digestion, energy homeostasis and metabolic regulation. While diurnal variation has been demonstrated in the enterohepatic circulation and the gut microbiota, existing human data are poorly resolved, and the influence of the host circadian system has not been determined. Using entrained laboratory protocols, we demonstrate robust daily rhythms in the circulating bile acid pool in healthy male participants. We identify temporal relationships between bile acids and plasma lipids and show that these relationships are lost following sleep deprivation. We also highlight that bile acid rhythmicity is predominantly lost when environmental timing cues are held constant. Here we show that the environment is a stronger determinant of these temporal dynamics than the intrinsic circadian system of the host. This has significance for the intimate relationship between circadian timing and metabolism., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Rumination shows a nocturnal rhythmic pattern in day-active ruminants. Although feeding has been shown to quantitatively modulate rumination, it is not clear yet if feeding rhythm plays a causal role in rumination rhythm. The present study was carried out to determine whether the daily rhythm of rumination in goats under natural environmental conditions is food-dependent or not, and whether it is modulated by the season. Rumination and locomotor activity (LA) were continuously monitored in four male Moroccan goats, fed once daily every morning, and then fasted for 4 days. The same experimental design was carried out in two different seasons (summer and winter). The results show that normally fed goats ruminate on average 281 ± 37 min in both seasons. Rumination shows a rhythmic 24-h profile with a late nocturnal peak. During the four-day food deprivation, rumination persisted while its total amount duration was significantly reduced in both seasons. Our results also illustrate the clear phase-opposition between the diurnal rhythm of LA and the nocturnal rhythm of rumination. This study characterized the daily rhythm rumination in goats according to seasons and fed/fasted states, and provided clear evidence that this rhythm is not generated by feeding behavior. Further investigations are required to determine whether rumination has an endogenous origin and is driven by the central circadian clock., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Reproductive mood disorders indicate that within-person variation in depressive symptoms across the menstrual cycle can be related to ovarian hormone changes. Until now, such cycle-related symptom changes have been measured once daily, even though depression research indicates systematic diurnal changes in symptoms. Further, previous research often focused on aggregated depression scores. This study examined whether three daily assessments of depressive symptoms follow similar trajectories across the menstrual cycle and investigated within-person cyclical fluctuation of all individual symptoms and the aggregated score., Methods: 77 naturally-cycling participants (35 with and 42 without depressive disorder) provided three daily ratings of depressive symptoms across one menstrual cycle to evaluate individual and summarized symptoms., Results: Reliability estimates (w) of the three diurnal measurements ranged from 0.56 to 0.78. Cyclicity showed statistically significant interindividual differences for all symptoms, and individual symptoms differed significantly from each other in their magnitude of cyclicity., Limitations: Only one menstrual cycle was assessed to reduce participant burden. Further, ovulation testing dates were based on self-reported cycle lengths, and only LH (luteinizing hormone) peaks were tested without subsequent progesterone rises., Conclusions: The results highlight the need for a symptom-specific approach to assess individual variance in cyclicity of depressive symptoms. Reliability for one daily assessment can be improved by using the afternoon value, a sum score for depressiveness, or multiple items per symptom. Furthermore, this study emphasizes, that depressive symptoms can systematically change across the menstrual cycle, and it is, therefore, important to include it in depression research. Exploring female-specific risk factors of depression will enable the development of person-tailored treatments., Trial Registration: The study was preregistered at ClinicalTrials.gov (NCT04086316) with the first registration on 27/08/2019., Competing Interests: Declarations Ethics approval and consent to participate The study was preregistered at ClinicalTrials.gov (NCT04086316) with the first registration on 27/08/2019 and approved by the local ethics committee at Freie Universität Berlin (ID: 003.2019). Informed consent to participate was obtained from all subjects. Consent to publish Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

It is increasingly clear that cellular metabolic function varies not just between cells of different tissues, but also within tissues and cell types. In this essay, we envision how differences in central carbon metabolism arise from multiple sources, including the cell cycle, circadian rhythms, intrinsic metabolic cycles, and others. We also discuss and compare methods that enable such variation to be detected, including single-cell metabolomics and RNA-sequencing. We pay particular attention to biosensors for AMPK and central carbon metabolites, which when used in combination with metabolic perturbations, provide clear evidence of cellular variance in metabolic function., (© 2024 The Author(s).)

The ability to anticipate tides is critical for a wide range of marine organisms, but this task is complicated by the diversity of tidal patterns on Earth. Previous findings suggest that organisms whose geographic range spans multiple types of tidal cycles can produce distinct patterns of rhythmic behavior that correspond to the tidal cycles they experience. How this behavioral plasticity is achieved, however, is unclear. Here, we show that Parhyale hawaiensis adapts its rhythmic behavior to various naturally occurring tidal regimens through the plastic contribution of its circatidal and circadian clocks. After entrainment to a tidal cycle that deviated only mildly from a regular 12.4 h tidal cycle, animals exhibited strong circatidal rhythms. By contrast, following entrainment to more irregularly spaced tides or to tides that occurred every 24.8 h, a significant fraction of animals instead synchronized to the light/dark (LD) cycle and exhibited circadian behavior, while others showed rhythmic behavior with both circatidal and circadian traits. We also show that the circatidal clock, while able to entrain to various naturally occurring tidal patterns, does not entrain to an unnatural one. We propose that Parhyale hawaiensis's ecological success around the world relies in part on the plastic interactions between the circatidal and circadian clocks, which shape its rhythmic behavior appropriately according to tidal patterns., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Key Message: We developed an in-house Python-based image analysis pipeline to investigate the movement patterns of Cuscuta. Our analysis unveiled that the coiling and circumnutation movements of Cuscuta are regulated by its intrinsic circadian rhythm. Cuscuta spp., commonly known as dodders, are rootless and leafless stem parasitic plants. Upon germination, Cuscuta starts rotating immediately in a counterclockwise direction (circumnutation) to locate a host plant, creating a seamless vascular connection to steal water and nutrients from its host. In this study, our aim was to elucidate the dynamics of the coiling patterns of Cuscuta, which is an essential step for successful parasitism. Using time-lapse photography, we recorded the circumnutation and coiling movements of C. campestris at different inoculation times on non-living hosts. Subsequent image analyses were facilitated through an in-house Python-based image processing pipeline to detect coiling locations, angles, initiation and completion times, and duration of coiling stages in between. The study revealed that the coiling efficacy of C. campestris varied with the inoculation time of day, showing higher success and faster initiation in morning than in evening. These observations suggest that Cuscuta, despite lacking leaves and a developed chloroplast, can discern photoperiod changes, significantly determining its parasitic efficiency. The automated image analysis results confirmed the reliability of our Python pipeline by aligning closely with manual annotations. This study provides significant insights into the parasitic strategies of C. campestris and demonstrates the potential of integrating computational image analysis in plant biology for exploring complex plant behaviors. Furthermore, this method provides an efficient tool for investigating plant movement dynamics, laying the foundation for future studies on mitigating the economic impacts of parasitic plants., Competing Interests: Declarations Conflict of interest All authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

An organism's biological processes are adapted to and driven by rhythmicity in the natural environment and periodicity of light is one of the most influential factors. In a developing organism, the onset of circadian rhythmicity might indicate the time point of functional necessity for aligning processes to the environment. Here, the circadian clock mechanism has been studied in the developing brain of Atlantic salmon (Salmo salar), by comparing the endogenous feeding alevin, independent on the environment for nutritional supply, to the exogenous feeding fry, dependent on the light period for detecting and catching prey. The results showed that while only a few clock genes were cyclic in the yolk sac alevins, many of the clock genes and genes of the circadian rhythm pathway cycled significantly in the feeding fry. Few genes were differentially expressed between time points in the circadian sampling series during the yolk sac stage, but several hundred genes were found differentially expressed in the first feeding stage. Genes important for cell cycle progression were cyclic or differentially expressed between time points after exogenous feeding, indicating a clock-controlled cell cycle at this stage. The expression of important genes in the melatonin synthesis were also cyclic in the feeding fry with an acrophase in the transition between light and dark or in darkness. Analyzing the impact of exogenous feeding on the developing brain supported a shift from utilization of proteins and lipids in the yolk to utilization and allocation of dietary energy and nutrients. Taken together, the life history transition related to onset of exogenous feeding is linked to the establishment of a persistent circadian rhythmicity in the salmon brain, which needs to be synchronized to light-dark cycles to enable the fry to search and capture feed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Eilertsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The suprachiasmatic nucleus (SCN) in the hypothalamus regulates circadian timing system (CTS) by co-ordinating peripheral tissue clocks and extra-SCN oscillators in the brain. Aging disrupts the CTS, impairing physiological functions and reducing antioxidant defences, which contribute to neurodegeneration. The brain is vulnerable to oxidative damage due to its high metabolic activity, oxygen consumption, and levels of iron and lipids. Antioxidant enzymes, such as catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxidation (LPO), help against oxidative damage. In this study, we examined the temporal patterns of these antioxidant stress indicators in the SCN and extra-SCN brain regions (frontal cortex, cerebellum, and hippocampus) at various time points in male Wistar rats 3, 12, and 24 months. The rhythmicity of GST and LPO levels persisted across brain regions with aging, while CAT rhythmicity was lost in the SCN and hippocampus of older rats. SOD rhythmicity persisted in cortex, cerebellum, and hippocampus but was lost in the SCN. The daily rhythm parameters of CAT were affected most significantly, followed by SOD, GST, and LPO. Our findings demonstrate that aging leads to desynchronization of oxidative stress indicators potentially contributing to neurodegeneration and circadian dysfunction with varying effects across different brain tissues., Competing Interests: Declarations Conflict of interest Authors declare they have no conflict., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose of Review: This review explores the role of the endocannabinoid system (ECS) in regulating energy balance, food intake, and metabolism, with a focus on how ECS dysregulation contributes to obesity. The goal is to provide insights into the mechanisms underlying obesity and its associated metabolic disorders., Recent Findings: Recent research indicates that the ECS significantly influences food intake, fat storage, insulin sensitivity, and inflammation, all of which are central to the development and progression of obesity. New research areas include the interaction between the ECS and gut microbiota, circadian rhythms of the ECS, and the impact of genetic and epigenetic factors on ECS function. Interest in the therapeutic potential of targeting the ECS has grown, with earlier treatments like CB1 receptor antagonists showing mixed results in efficacy and safety. Evidence from both animal and human studies highlight the impact of elevated levels of the endocannabinoids anandamide and 2-AG on food intake, insulin resistance, visceral fat accumulation, and metabolic disturbances associated with obesity. The review explores the interaction between the ECS and other physiological systems, including gut-brain communication, circadian rhythms, as well as leptin and ghrelin signaling. Additionally, genetic and epigenetic factors influencing ECS function are examined, emphasizing their contribution to obesity susceptibility. While therapeutic approaches targeting the ECS, particularly CB1 receptor antagonism, have shown potential in managing obesity, the review acknowledges the challenges posed by central nervous system side effects in earlier treatments like rimonabant. However, recent advancements in peripherally restricted CB1 antagonists offer renewed hope for safer and more effective obesity treatments. The review concludes by addressing future research directions and therapeutic strategies to combat this global health challenge., Competing Interests: Declarations Human and Animal Rights All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines). Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Artificial light at night (ALAN) changes animal behavior in multiple invertebrates and vertebrates and can result in decreased fitness. However, ALAN effects have not been studied in European honey bees (Apis mellifera), an important pollinator in which foragers show strong circadian rhythmicity. Colonies can be exposed to ALAN in swarm clusters, when bees cluster outside the nest on hot days and evenings, and, in limited cases, when they build nests in the open. We captured and maintained foragers in incubated cages and subjected them to constant light (LL), constant dark (DD), or 12 h light:12 h dark (LD) cycle, and observed them with infrared cameras. After 79 h, there was a significant interaction of treatment and time because LL bees slept less. In detail, the bees maintained a regular sleep pattern for three days but LL bees showed a shift on the fourth day. LL bees had the largest sleep differences from LD controls, with trends of lengthened periods and increased phase misalignment from both LD and DD bees. LL bees also experienced significantly more disturbances from their nestmates and preferred to sleep in the lower portion of the cages, which had significantly lower light intensity. These findings suggest that ALAN can disrupt the sleep of honey bee foragers, which has implications for their behavior and overall colony health., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to analyze vital sign characteristics of adult patients admitted at the Tertiary Hospital, and to define fever threshold and average body temperature by examining the tympanic temperatures of all patients. Retrospective medical data were extracted from 9195 patients aged > 21 years admitted to a tertiary hospital for elective surgeries between 2016 and 2020. Data regarding the patients' vital signs during their hospital stay, including tympanic body temperature, heart rate, and respiratory rate, were analyzed according to age, sex, and circadian rhythm. A normal-distribution graph was obtained when all the body temperature results were aligned. The average body temperature measured was 36.91 ± 0.45 °C (average ± standard deviation), indicating a potential fever threshold of 37.81 °C. When the participants were divided into age groups, the average temperature, heart rate, and respiratory rate exhibited parabolic trends. Patients in their 60s exhibited the lowest average temperature (36.88 °C), whereas those in their 50s had the lowest average heart rate (75.82/min) and lowest respiratory rate (19.08/min). Heart rate and respiratory rate tended to increase in elderly people older than 81 years. The average body temperature was greater in women than in men (36.94 ± 0.42 °C vs. 36.89 ± 0.47 °C), while the average heart (75.53 ± 10.04/min vs. 77.31 ± 11.52/min) and respiratory rates (19.13 ± 1.39/min vs. 19.29 ± 2.24/min) were lower in women than in men respectively. According to the time of measurement, the average temperature and heart rate appeared to follow a sinusoidal pattern, suggesting that the circadian rhythm was highest at 1 a.m. and lowest at 8 a.m. Tympanic temperature is a convenient measurement method preferred in hospital settings because it is noninvasive and easier to measure compared to other body parts. To develop an improved device and measurement method in the future, it is necessary to analyze tympanic temperature big data and compare it with past vital sign data or biometric information from other body parts., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The blood-brain barrier (BBB) is critical for maintaining brain homeostasis but is susceptible to inflammatory dysfunction. While transporter-dependent efflux of some lipophilic substrates across the BBB shows circadian variation due to rhythmic transporter expression, basal transporter-independent permeability and leakage is nonrhythmic. Whether daily timing influences BBB permeability in response to inflammation is unknown. Here, we induced systemic inflammation through repeated LPS injections either in the morning (ZT1) or evening (ZT13) under standard lighting conditions; we then examined BBB permeability to a polar molecule that is not a transporter substrate, sodium fluorescein. We observed clear diurnal variation in inflammatory BBB permeability, with a striking increase in paracellular leak across the BBB specifically following evening LPS injection. Evening LPS led to persisting glia activation as well as inflammation in the brain that was not observed in the periphery. The exaggerated evening neuroinflammation and BBB disruption were suppressed by microglial depletion or through keeping mice in constant darkness. Our data show that diurnal rhythms in microglial inflammatory responses to LPS drive daily variability in BBB breakdown and reveal time of day as a key regulator of inflammatory BBB disruption.

Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.

Background: Despite the potential effectiveness of bariatric surgery in promoting weight loss, a considerable proportion of patients still face the challenge of achieving optimal post-surgery outcomes. The timing of eating, in addition to the content of what is eaten, as well as chronotype and social jetlag (a marker of circadian misalignment), have been implicated in weight regulation. However, the current understanding of these chrono-related behaviours in individuals undergoing bariatric surgery is still scarce. Thus, this study aims to evaluate the role of chrono-nutrition, chronotype, and circadian misalignment in the weight-loss trajectory among individuals living with severe obesity who underwent bariatric surgery., Methods: The ChronoWise project is a prospective single-centre cohort study designed to follow patients experiencing bariatric surgery at the Santo António Local Health Unit (ULSSA), Porto, Portugal. Participants will be recruited and evaluated at pre-surgery and followed-up over 3 and 6 months after surgery. The baseline evaluation will be conducted face-to-face during the hospital stay and by telephone or video call on the subsequent evaluations, following standard procedures. Data collection includes sociodemographics, food intake, chrono-nutrition behaviours, sleep time behaviour, sleep quality, screen time, physical activity and exercise behaviours, anthropometric measurements, and biochemical parameters. The 'Munich Chronotype Questionnaire' will be used to assess chronotype and social jet lag. Chrono-nutrition dimensions will be measured by the 'Chrononutrition Profile-Questionnaire' in all evaluations. Weight and height will be self-reported and retrieved from medical registries. trajectories of weight-loss will be obtained., Discussion: This study will add important evidence on the role of chrono-nutrition, chronotype and social jetlag profile in weight-loss outcomes after bariatric surgery. Identifying novel approaches to change the paradigm of post-surgical weight management towards a tailored treatment aligned with circadian rhythm may be useful to strengthen the existing treatments and improve patients' response to bariatric surgery., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Rodrigues et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The hepatic vagal nerve mediates the impact of circadian disruption on food intake in mice.

Study Objectives: Shiftwork is associated with cognitive impairment and reduced sleep time and quality, largely due to circadian misalignment. This study tested if circadian-informed lighting could improve cognitive performance and sleep during simulated night shifts versus dim control lighting., Methods: Nineteen healthy participants (mean ± SD 29 ± 10 years, 12 males, 7 females) were recruited to a laboratory study consisting of two counterbalanced 8-day lighting conditions (order randomized) 1-month apart: (1) control lighting condition - dim, blue-depleted and (2) circadian-informed lighting condition - blue-enriched and blue-depleted where appropriate. Participants underwent an adaptation night (22:00-07:00 hours), then four nights of simulated night work (cognitive testing battery of nine tasks, 00:00-08:00 hours), and sleep during the day (10:00-19:00 hours). Psychomotor vigilance task (PVT) lapses, Karolinska Sleepiness Scale (KSS) scores, and polysomnography-derived sleep outcomes were compared between conditions and across days using mixed models., Results: Significant condition-by-day-by-time of task interaction effects were found for PVT lapses, median reaction time, and reaction speed, with ~50% fewer lapses by the end of simulated shift work with circadian-informed lighting versus control (mean ± SD 7.4 ± 5.0 vs. 15.6 ± 6.1). KSS was lower around the night shift midpoints on days 6 and 7 with circadian versus control lighting. Participants slept 52 minutes longer [95% CIs: 27.5, 76.5 minutes] by day 7 with circadian-informed versus control lighting, p < .001. Effects were inconsistent on other performance tasks., Conclusions: Circadian-informed lighting improved sleep, sleepiness, and vigilance compared to control lighting. These findings support the potential for lighting interventions to improve sleep and vigilance in night shift workers chronically exposed to dim lighting., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Study Objective: Night work has detrimental impacts on sleep and performance, primarily due to misalignment between sleep-wake schedules and underlying circadian rhythms. This study tested whether circadian-informed lighting accelerated circadian phase delay, and thus adjustment to night work, compared to blue-depleted standard lighting under simulated submariner work conditions., Methods: Nineteen healthy sleepers (12 males; mean ± SD aged 29 ± 10 years) participated in two separate 8-day visits approximately 1 month apart to receive, in random order, circadian-informed lighting (blue-enriched and dim, blue-depleted lighting at specific times) and standard lighting (dim, blue-depleted lighting). After an adaptation night (day 1), salivary dim-light melatonin onset (DLMO) assessment was undertaken from 18:00 to 02:00 on days 2-3. During days 3-7, participants completed simulated night work from 00:00 to 08:00 and a sleep period from 10:00 to 19:00. Post-condition DLMO assessment occurred from 21:00 to 13:00 on days 7-8. Ingestible capsules continuously sampled temperature to estimate daily core body temperature minimum (Tmin) time. Tmin and DLMO circadian delays were compared between conditions using mixed effects models., Results: There were significant condition-by-day interactions in Tmin and DLMO delays (both p < .001). After four simulated night shifts, circadian-informed lighting produced a mean [95% CI] 5.6 [3.0 to 8.2] hours greater delay in Tmin timing and a 4.2 [3.0 to 5.5] hours greater delay in DLMO timing compared to standard lighting., Conclusions: Circadian-informed lighting accelerates adjustment to shiftwork in a simulated submariner work environment. Circadian lighting interventions warrant consideration in any dimly lit and blue-depleted work environments where circadian adjustment is relevant to help enhance human performance, safety, and health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Study Objectives: Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity., Methods: In this cross-sectional study, we extracted the RNA repeatedly across 24 hours from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using six consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers)., Results: With napping, there was an 88% decrease in the number of rhythmic genes compared to that in non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes upregulated in nappers. The top upregulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation., Conclusions: These new findings have implications for our understanding of napping's relationship with obesity and metabolic disorders., (Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2024.)

Background: Myopia is a growing healthcare concern worldwide. Increasing evidence suggests that sleep and circadian rhythms may be associated with myopia. Furthermore, the risk factors of myopia have not been studied in the Estonian population to date. This study aimed to evaluate chronotype, lifestyle factors, and parental myopia in relation to myopia in Estonian secondary school students., Methods: Grade 10 students from three secondary schools in Tallinn, each with distinct focuses: one science-oriented, one arts-oriented, and one sports-oriented, were invited to participate. They underwent a comprehensive ocular examination, including cycloplegic autorefraction and ocular biometry. Chronotype was evaluated with the Morningness - Eveningness Questionnaire. Participants reported parental myopia and replied to a set of questions, separately for schooldays and free days, to indicate the amount of time they spent outdoors, doing near work and intermediate distance activities. Myopia was defined as cycloplegic SER ≤ - 0.50 D. Logistic regression analysis was performed to assess the association of the studied factors with myopia., Results: A total of 123 students (57% female) participated in the study, with a mean age of 16.71 years (standard deviation 0.41). In a multivariable regression model, having two myopic parents was associated with higher odds of myopia (OR 3.78, 95% CI 1.15 - 12.42). We found no association between myopia and chronotype. Notably, time spent outdoors and doing near work or intermediate distance work did not affect the likelihood of having myopia. We observed that students attending the sports-oriented school had lower odds of myopia than those attending the science-oriented school (OR 0.12, 95% CI 0.03-0.51)., Conclusion: Chronotype was not associated with myopia in our study sample. Consistent with previous reports, we identified parental myopia as a myopia risk factor. Interestingly, there was no association between myopia and time spent outdoors or near work. However, the odds of myopia varied depending on the school attended by the participants, which may reflect the educational load or lifestyle of participants in earlier childhood., (© 2024. The Author(s).)

How can a single protein domain encode a conformational landscape with multiple stably folded states, and how do those states interconvert? Here, we use real-time and relaxation-dispersion NMR to characterize the conformational landscape of the circadian rhythm protein KaiB from Rhodobacter sphaeroides . Unique among known natural metamorphic proteins, this KaiB variant spontaneously interconverts between two monomeric states: the "Ground" and "Fold-switched" (FS) states. KaiB in its FS state interacts with multiple binding partners, including the central KaiC protein, to regulate circadian rhythms. We find that KaiB itself takes hours to interconvert between the Ground and FS state, underscoring the ability of a single-sequence to encode the slow process needed for function. We reveal the rate-limiting step between the Ground and FS state is the cis-trans isomerization of three prolines in the fold-switching region by demonstrating interconversion acceleration by the prolyl isomerase Cyclophilin A. The interconversion proceeds through a "partially disordered" (PD) state, where the C-terminal half becomes disordered while the N-terminal half remains stably folded. We found two additional properties of KaiB's landscape. First, the Ground state experiences cold denaturation: At 4 °C, the PD state becomes the majorly populated state. Second, the Ground state exchanges with a fourth state, the "Enigma" state, on the millisecond-timescale. We combine AlphaFold2-based predictions and NMR chemical shift predictions to predict this Enigma state is a beta-strand register shift that relieves buried charged residues, and support this structure experimentally. These results provide mechanistic insight into how evolution can design a single-sequence that achieves specific timing needed for its function., Competing Interests: Competing interests statement:D.K. is a co-founder of Relay Therapeutics and MOMA Therapeutics. The remaining authors declare no competing interests.

The circadian oscillation of gut microbiota plays vital roles in the normal physiology and health of the host. Although the diurnal oscillation of intestinal bacteria has been extensively studied, little relevant work has been done on intestinal fungi. Besides, the rhythmic correlations between bacterial and fungal microbes are also scarcely reported. Here, we investigated the diurnal oscillations of bacterial and fungal communities in male cynomolgus monkeys by performing 16S rRNA and ITS amplicon sequencing. As for bacterial genera, we found that the relative abundance of Prevotella , norank&#95;f&#95;Eubacterium&#95;coprostanoligenes&#95;group, and Peptococcus underwent significant changes at ZT12 (19:00) and exhibited obvious rhythmic oscillations. Consequently, most of the bacterial functions varied at ZT12 and were positively correlated with the bacterial genera norank&#95;f&#95;Eubacterium&#95;coprostanoligenes&#95;group and Prevotella . Among the fungal genera, the relative abundance of Aspergillus and Talaromyces decreased at ZT18 (1:00) and showed slight rhythmic oscillations. As for the fungal function, the undefined saprotroph showed slight rhythmic oscillation and was positively correlated with the fungal genus Aspergillus . Notably, we characterized the correlations between intestinal bacteria and fungi every 6 h over the course of a day and found that the bacterial and fungal microbes interacted closely, with the most bacteria-fungi interactions occurring at ZT12. Our study contributed to a more comprehensive understanding of the diurnal oscillation patterns of bacterial and fungal microbes in male cynomolgus monkeys and uncovered their correlations during a diurnal cycle., Importance: The rhythmic oscillation of gut microbiota can impact the physiology activity and disease susceptibility of the host. Until now, most of the studies are focused on bacterial microbes, ignoring other components of gut microbes, such as fungal microbes (mycobiota). Besides, only few studies have addressed the rhythmic correlations between gut bacteria and fungi. Here, we analyzed the rhythmic oscillations of bacterial and fungal communities in male cynomolgus monkeys by performing 16S rRNA and ITS amplicon sequencing. Apart from identifying the rhythmically oscillated bacterial and fungal microbes, we conducted the correlation analysis between these two microbial communities and found that the intestinal bacteria and fungi exhibited close interactions rhythmically, with the most interactions occurring at ZT12. Thus, our study not only investigated the rhythmic oscillations of gut bacterial and fungal communities in male cynomolgus monkeys but also uncovered their rhythmic interactions., Competing Interests: The authors declare no conflict of interest.

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by inflammatory activity with distinct rhythmic fluctuations. However, the precise mechanisms governing these inflammatory rhythms remain elusive. Here, we explore the interaction between dietary patterns, gut microbiota diurnal oscillations, and the rhythmicity of RA in both collagen-induced arthritis (CIA) mice and patients with RA and highlight the significance of dietary timing in modulating RA inflammatory rhythms linked to gut microbiota. Specifically, we discovered that Parabacteroides distasonis (P. distasonis) uses β-glucosidase (β-GC) to release glycitein (GLY) from the diet in response to daily nutritional cues, influencing RA inflammatory rhythms dependent on the sirtuin 5-nuclear factor-κB (SIRT5-NF-κB) axis. Notably, we validated the daily fluctuations of P. distasonis-β-GC-GLY in patients with RA through continuous sampling across day-night cycles. These findings underscore the crucial role of dietary timing in RA rhythmicity and propose potential clinical implications for novel therapeutic strategies to alleviate arthritis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The operation of the retina, like other brain circuits, is under modulatory control. One coordinator of changes in retinal function is dopamine, a neuromodulator released in a light-dependent way to adjust vision on a diurnal cycle. Here, we demonstrate that substance P is a similarly powerful retinal modulator that interacts with the dopamine system. By imaging glutamatergic synaptic transmission in larval zebrafish, we find that substance P decreases the contrast sensitivity of ON and OFF visual channels up to 8-fold, with suppression of visual signals being strongest through the "transient" pathway responding to higher frequencies. These actions are exerted in the morning, in large part by suppressing the amplification of visual signals by dopamine, but substance P is almost completely inactive in the afternoon. Modulation of retinal gain is accompanied by changes in patterns of vesicle release at the synapses of bipolar cells: increased gain shifts coding of stimulus strength from the rate of release events to their amplitude generated by a process of multivesicular release (MVR). Together, these actions of substance P reduce the flow of visual information, measured in bits, ∼3-fold. Thus, whereas dopamine "pushes" the retina to transmit information at higher rates in the afternoon, substance P acts in antiphase to suppress dopamine signaling and "pull down" information transmission in the morning., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Time in headache disorders is crucial for diagnosis and gives insight into headache pathophysiology., Objective: To summarize published studies which describe timing processes in both attack presentation (onset, duration) and disease characterization (age of onset, evolution over time) in primary headache disorders and link to pathophysiology., Methods: A comprehensive search was conducted through Ovid MEDLINE(R) and PubMed, focusing on English-language articles from 1946 to 2023 to write the review. The International Classification of Headache Disorders, 3rd edition provided the framework for the review of primary headache disorders (migraine, tension-type headache and cluster headache)., Results: Attack presentation : Migraine attacks exhibit significant circadian and infradian rhythms, influenced by hormonal levels, light sensitivity, and hypothalamic activation. Tension-type headache lacks clear chronobiological patterns, with limited understanding of its underlying mechanisms. Cluster headache displays a distinct circannual pattern, with attacks often occurring at night and relevant involvement of the hypothalamus. Disease characterization : Age of onset exhibits the earliest peak in migraine; frequency and typical features of primary headache disorders decrease over time., Conclusion: This comprehensive analysis of time patterns in primary headache disorders underscores their role in phenotyping, understanding and treating primary headache disorders, offering promising avenues for advancing and tailoring headache management., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.G.M. reports that within the prior 36 months has received speaker honoraria from TEVA, Lilly and Altermedica.J.C.R reports in the last 36 months he has received honoraria for education presentations for Abbvie, Novartis and Viatris. He has served on medical advisory boards for Pfizer, Viatris and Lilly. His institution has received funding for research grants, clinical trials and projects supported by the International Headache Society, Brain Foundation, Lundbeck, Abbvie, Pfizer and Aeon.F.H., F.J.O., H.G., T.C.S., M.C.D., U.A., H.H., J.M.K., reports no conflict of interests.K.S.L reports personal fees from Teva and Acticor Biotech.E.C. has received received honoraria from Novartis, Chiesi, Lundbeck, Medscape.P.P.R. reports that within the prior 36 months, having received honoraria as a consultant and speaker for: AbbVie, Amgen, Biohaven, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer and Teva. Her research group has received research grants from Novartis, Teva, AbbVie, EraNET Neuron, RIS3CAT FEDER, AGAUR, ISCIII, International Headache Society; has received funding for clinical trials from Alder, Amgen, Biohaven, Eli Lilly, Lundbeck, Novartis, Teva. She is the Honorary Secretary of the International Headache Society. She is a member of the Clinical Trials Guideline Committee of the International Headache Society. She serves as an associate editor for Cephalalgia, Headache, The Journal of Headache and Pain, Neurologia, and Revista de Neurologia. She is the founder of www.midolordecabeza.org. P.P.R. does not own stocks from any pharmaceutical company.

Background:  Alterations of the autonomic nervous system (ANS) in the chronic stage of ischemic stroke (IS) are not well understood. Heart rate variability (HRV) provides a noninvasive approach to assess autonomic function., Objective:  To compare the HRV parameters during the sleep-wake cycle between patients with IS in the chronic stage and healthy subjects., Methods:  We conducted a retrospective transversal study based on clinical records and 24-hour electrocardiogram (EKG) monitoring registries of 179 patients with a confirmed IS diagnosis and 184 age- and sex-matched healthy subjects. Circadian variation was calculated according to the variation of the total autonomic activity (VTAI) and the parasympathetic activity (VPAI) indexes. Comparisons were performed using nonparametric tests. Multivariable analyses were performed with canonical discriminant analysis (CDA) and a three-way analysis of variance (ANOVA). Statistical significance was established with a confidence level of 95%., Results:  During waking hours, the healthy group exhibited higher variability in the time domain and frequency domain parameters: standard deviation of NN intervals (SDNN, p  < 0.001) and of the average NN intervals (SDANN, p  < 0.001), as well as low-frequency (LF) band ( p  < 0.001). During sleep, the difference was higher in the high-frequency (HF) band ( p  < 0.001), and lower in the low-/high-frequency ratio (LF/HF, p  < 0.001). Both VPAI and VTAI showed less significant difference in IS patients ( p  < 0.001)., Conclusion:  There was diminished heart vagal activity among IS patients, as measured through HRV. During sleep, this is likely caused by an imbalance in the sympathetic and parasympathetic systems shifting through the sleep phases. These imbalances could persist over time in patients with IS, lasting months after the initial injury., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Olfaction is a critical sensory modality for invertebrates, and it mediates a wide range of behaviors and physiological processes. Like most living organisms, insects live in rhythmic environments: the succession of nights and days is accompanied by cyclic variations in light intensity and temperature, as well as in the availability of resources and the activity of predators. Responding to olfactory cues in the proper temporal context is thus highly adaptive and allows for the efficient allocation of energy resources. Given the agricultural or epidemiological importance of some insect species, understanding olfactory rhythms is critical for the development of effective control strategies. Although the vinegar fly Drosophila melanogaster has been a classical model for the study of olfaction and circadian rhythms, recent studies focusing on non-model species have expanded our understanding of insect olfactory rhythms. Additionally, recent evidence revealing receptor co-expression by sensory neurons has brought about an ongoing paradigm shift in our understanding of insect olfaction, making it timely to review the state of our knowledge on olfactory rhythms and identify critical future directions for the field. In this Review, we discuss the multiple biological scales at which insect olfactory rhythms are being analyzed, and identify outstanding questions., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: We aimed to examine whether current and lifetime night shift work is associated with accelerated biological ageing and the potential role of body mass index (BMI) in mediating the association., Methods: Data were sourced from the UK Biobank cohort. This study included participants who reported detailed information on their current work schedule and had complete data to calculate PhenoAge. The outcome of interest was biological ageing, measured by PhenoAge acceleration. Multivariable linear regression models were conducted to test the relationship between night shift work and biological ageing. Mediation analyses were performed., Results: Of the 182 064 participants included, the mean age was 52.6 years, and 51.1% were male. After adjustment for chronological age and sex, compared with day workers, shift workers without night shift, irregular night shift workers and permanent night shift workers were associated with 0.59-, 0.87- and 1.30-year increase in biological ageing, respectively (P for trend <.001). Considering the lifetime work schedule, participants who worked night shifts >10 years and participants who worked >8 night shifts each month showed increased biological age acceleration [>10 years: β = 0.54, 95% confidence interval (CI) 0.29-0.79; >8 times/month: β = 0.29, 95% CI 0.07-0.50]. The mediation analysis showed that BMI mediated the associations between night shift work and biological age acceleration by 36%-53%., Conclusions: We showed that night shift work was associated with accelerated biological ageing. Our findings highlight the interventions on appropriate shift work schedules and weight management in night shift workers, which may slow the biological ageing process and ultimately reduce the burden of age-related diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent changes in peripheral rhythms, we compared the ability of human serum from young and old individuals to synchronize circadian rhythms in culture. We collected blood from apparently healthy young (age 25-30) and old (age 70-76) individuals at 14:00 and used the serum to synchronize cultured fibroblasts. We found that young and old sera are equally competent at initiating robust ~24 hr oscillations of a luciferase reporter driven by clock gene promoter. However, cyclic gene expression is affected, such that young and old sera promote cycling of different sets of genes. Genes that lose rhythmicity with old serum entrainment are associated with oxidative phosphorylation and Alzheimer's Disease as identified by STRING and IPA analyses. Conversely, the expression of cycling genes associated with cholesterol biosynthesis increased in the cells entrained with old serum. Genes involved in the cell cycle and transcription/translation remain rhythmic in both conditions. We did not observe a global difference in the distribution of phase between groups, but found that peak expression of several clock-controlled genes ( PER3, NR1D1, NR1D2, CRY1, CRY2, and TEF ) lagged in the cells synchronized ex vivo with old serum. Taken together, these findings demonstrate that age-dependent blood-borne factors affect circadian rhythms in peripheral cells and have the potential to impact health and disease via maintaining or disrupting rhythms respectively., Competing Interests: JS, AM, NL, YL, CH, GG, CS, SZ No competing interests declared, AS Reviewing editor, eLife, (© 2023, Schwarz et al.)

Background: Prader-Willi Syndrome (PWS) is a genetic neurodevelopmental disorder marked by disruptions in circadian rhythms and autonomic nervous system (ANS) activity, hyperphagia, and episodes of emotional outbursts. Previous trials suggest that both invasive and non-invasive vagus nerve stimulation (VNS) can reduce emotional outbursts in PWS, potentially through its effects on vagal activity., Aim: This case series investigated the effects of transcutaneous auricular VNS (taVNS) on cardiac markers of circadian vagal activity, specifically heart rate variability (HRV) and heart rate (HR), and their potential links to improvements in emotional outbursts., Methods: Five individuals with PWS (mean age: 26.9 years; 3 males, 2 females) received four hours of daily taVNS for 12 months, followed by one month of two-hour daily sessions. Outcome measures included daily recording of emotional outbursts and every three months 24-h HRV and HR recordings. Mixed cosinor models were applied to analyze changes in circadian rhythms of HRV and HR. A linear mixed model was used to assess the predictive value of cardiac vagal activity on emotional outbursts., Results: Circadian amplitudes of HRV and HR were significantly higher at the end of the treatment compared to baseline (all p's < .01). There was a significant increase in the rhythm-adjusted mean of HRV (p < .01), while the rhythm-adjusted HR mean significantly decreased, both indicating increased cardiac vagal activity. Higher rhythm-adjusted mean HRV predicted a lower number of emotional outbursts., Conclusion: The results suggest that taVNS may be effective by targeting ANS activity in individuals with PWS, contributing to improvements in behavioral regulation., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The liver has many functions including the regulation of nutrient and metabolite levels in the systemic circulation through efficient transport into and out of hepatocytes. To sustain these functions, hepatocytes display large functional heterogeneity. This heterogeneity is reflected by zonation of metabolic processes that take place in different zones of the liver lobule, where nutrient-rich blood enters the liver in the periportal zone and flows through the mid-zone prior to drainage by a central vein in the pericentral zone. Metabolite transport plays a pivotal role in the division of labor across liver zones, being either transport into the hepatocyte or transport between hepatocytes through the blood. Signaling pathways that regulate zonation, such as Wnt/β-catenin, have been shown to play a causal role in the development of metabolic dysfunction-associated steatohepatitis (MASH) progression, but the (patho)physiological regulation of metabolite transport remains enigmatic. Despite the practical challenges to separately study individual liver zones, technological advancements in the recent years have greatly improved insight in spatially divided metabolite transport. This review summarizes the theories behind the regulation of zonation, diurnal rhythms and their effect on metabolic zonation, contemporary techniques used to study zonation and current technological challenges, and discusses the current view on spatial and temporal metabolite transport., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Purpose: To evaluate and quantify variation of biometric parameters - axial length (AL), anterior chamber depth (ACD), central corneal thickness (CCT) and white-to-white (WTW)., Methods: A population-based retrospective cohort study was performed on patients who underwent a biometry test prior to cataract surgery using the IOL Master 700 (Carl Zeiss Meditec, Jena, Germany) between the years 2017-2021. Differences in these parameters were evaluated between scans executed at different times of the day., Results: 21,975 examinations of 8611 patients were included. Mean age was 70.50±12.56years. The mean time of the biometry exams was 10:52±1:23 AM. Measurements of AL, ACD, CCT and WTW were tested hourly and grouped between 7:00-9:00 AM and 12:00-03:00 PM. All the parameters showed a diurnal increase with a significance of P<0.001 (AL from 23.64±1.5 to 24.01±1.76mm; ACD from 3.29±0.67 to 3.35±0.64mm; CCT from 0.52±0.04 to 0.53±0.04μm and WTW from11.83±0.46 to 11.90±0.51mm). The most significant change was seen in AL. The difference between time groups remained significant in a generalized linear mixed model (P<0.001)., Conclusions: There are fluctuations in AL, ACD, CCT, WTW measurements during office hours. These results raise questions about the significance of timing of the biometry exam and the effect on the ELP calculation., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Bipolar Disorder (BD) is associated with alterations of circadian rhythms of activity (CRA). Experimental research suggests that lithium (Li) modifies CRA, but this has been rarely explored in BD using actigraphy., Methods: The sample comprised 88 euthymic BD-I cases with 3 weeks of actigraphy. We used a Principal Component Analysis (PCA) to generate CRA dimensions. We then used linear regression analyses to compare these dimensions between groups of individuals defined according to prescribed mood stabilizers: Li monotherapy ("Li" group, n = 28), anticonvulsant or atypical antipsychotic monotherapy ("AC or AAP" group, n = 27) or combined treatments ("Li+AC or Li+AAP" group, n = 33). Analyses were adjusted for potential confounders (gender, age, body mass index, depressive symptoms, co-prescribed benzodiazepines and antidepressants, smoking status and past alcohol use disorder)., Results: The PCA identified two dimensions: "robust CRA" (high amplitude and interdaily stability, with low intradaily variability) and "late chronotype". Univariate analyses showed higher scores for "robust CRA" in the "Li" versus the "AC or AAP" (p = 0.021) or "Li+AC or Li+AAP" groups (p = 0.047). These findings remained significant after adjustments (respectively p = 0.010 and p = 0.019). Post-hoc analyses suggested lower variability, higher stability and higher amplitude of CRA in the "Li" group. Medication groups were similar for the "late chronotype" dimension (p = 0.92)., Conclusions: This actigraphy study is the first to show more favorable CRA in BD-I individuals receiving a Li monotherapy when compared with those receiving other classes or combinations of mood stabilizers. Replications in larger samples are required. Prospective studies are also warranted to elucidate whether the introduction of Li or other mood stabilizers might influence CRA in BD-I., Competing Interests: Declaration of competing interest B.E. has received honoraria for consulting from Sanofi. F.B. is an advisor on mental health to the French government. All other authors have no conflict of interest regarding this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Circadian rhythms are 24-h rhythms governing temporal organization of behavior and physiology generated by molecular clocks composed of autoregulatory transcription-translation feedback loops (TTFLs). Disruption of circadian rhythms leads to a spectrum of pathologies, including cancer by triggering or being involved in different hallmarks. Clock control of phenotypic plasticity involved in tumorigenesis operates in aberrant dedifferentiating to progenitor-like cell states, generation of cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) events. Circadian rhythms might act as candidates for regulatory mechanisms of cellular senescent and functional determinants of senescence-associated secretory phenotype (SASP). Reciprocal control between clock and epigenetics sheds light on post-transcriptional regulation of circadian rhythms and opens avenues for novel anti-cancer strategies. Additionally, disrupting circadian rhythms influences microbiota communities that could be associated with altered homeostasis contributing to cancer development. Herein, we summarize recent advances in support of the nexus between disruptions of circadian rhythms and cancer hallmarks of new dimensions, thus providing novel perspectives on potentially effective treatment approaches for cancer management., Competing Interests: Declaration of competing interest We claim the following statements: No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Research and theory suggest an important role of neuroendocrine function in emotional development, particularly under conditions of elevated stress. We provide empirical data to clarify associations between alpha-amylase (AA) and cortisol as well as test the differential linkages among AA, cortisol, and symptoms of anxiety, depression, and posttraumatic stress in children. Children recruited from a low-income elevated violence community (n = 100; mean age = 10, SD = 0.64; 79% Latino; 67% received free or reduced lunch) were assessed on diurnal levels of AA and cortisol along with assessments of anxiety, depression, and posttraumatic stress symptoms (PTSS). Elevated anxiety symptoms were associated with steeper linear slopes of AA with higher levels of AA in the morning but lower levels of AA in the evening. Depression was associated with differential cubic trajectories of AA when PTSSs were included in the model. Anxiety also predicted differential cubic diurnal trends in cortisol, such that greater anxiety symptoms were associated with relatively higher levels of cortisol in the evening. Again, depression symptoms when PTSS were included predicted diurnal cubic trends with elevated depression associated with lower awakening and midday cortisol that reversed to higher evening cortisol compared to youth with fewer self-reported depression symptoms., (© 2024 The Author(s). Developmental Psychobiology published by Wiley Periodicals LLC.)

The second-meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 h of morning hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon hyperinsulinemic-hyperglycemic (HIHG) clamp. Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the afternoon response to a HIHG clamp. To determine this, the same total amount of insulin was administered either over 2 h in the first (Ins2h-A) or second (Ins2h-B) half of the morning or over the entire 4 h (Ins4h) of the morning. In the 4-h afternoon period, all three groups had 4x-basal insulin, 2x-basal glycemia, and portal glucose infusion to expose the liver to the primary postprandial regulators of hepatic glucose metabolism. During the afternoon clamp, there was a marked increase in HGU and hepatic glycogen synthesis in the Ins4h group compared with the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose loads and total insulin infusion rates. Thus, the longer duration (Ins4h) of lower hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the afternoon clamp. NEW & NOTEWORTHY Morning insulin exposure primes the liver for increased hepatic glucose uptake and glycogen storage during a subsequent hyperinsulinemic-hyperglycemic clamp. This study addressed whether the pattern and/or duration of insulin delivery in the morning influences insulin's ensuing priming effect. We found that despite receiving equal total doses of insulin in the morning, a prolonged, lower rate of morning insulin delivery improved afternoon liver glucose metabolism more effectively than a shorter, higher rate of delivery.

Although hypertension is highly prevalent among the elderly and significantly contributes to cardiovascular disease risk, studies focusing on male elderly individuals over 85 years old are relatively scarce. This study aimed to investigate ambulatory blood pressure monitoring (ABPM) characteristics in male hypertensive patients aged over 85 years. These included demographic characteristics, antihypertensive drug use, 24-h ABPM values, diabetes, coronary heart disease, sleep disorders, smoking history, and drinking history, and the differences in ABPM between the age groups over and under 85 years old were analyzed. A total of 585 elderly hypertensive patients were included. The mean systolic blood pressure in individuals aged over 85 years was significantly greater throughout the day (131.57 ± 12.52 mmHg vs. 123.75 ± 2.74 mmHg, p < .001). In the 85 years older age group, the nighttime variability coefficient of SBP was lower at 7.84 ± 2.9 than the under 85 years age group 8.92 ± 3.13 (p < .001). The 85 years older age group age group presented a significantly greater whole-day systolic blood pressure standard deviation of ABPM (13.2 ± 3.19 vs. 12.47 ± 3.05, p = .005) compared with those under the age of 85 years. In the 85 years older age group, the proportion of individuals with the reverse dipper pattern was higher (48.15% vs. 38.31%, p = .017) than under 85 years age group. This study revealed that elderly male hypertensive patients aged over 85 years presented elevated average blood pressure levels. The research investigated ABPM characteristics. Older hypertensive individuals are more likely to have a reverse-dipper blood pressure pattern., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

A new mathematical model of melatonin synthesis in pineal cells is created and connected to a slightly modified previously created model of the circadian clock in the suprachiasmatic nucleus (SCN). The SCN influences the production of melatonin by upregulating two key enzymes in the pineal. The melatonin produced enters the blood and the cerebrospinal fluid and thus the SCN, influencing the circadian clock. We show that the model of melatonin synthesis corresponds well with extant experimental data and responds similarly to clinical experiments on bright light in the middle of the night. Melatonin is widely used to treat jet lag and sleep disorders. We show how the feedback from the pineal to the SCN causes phase resetting of the circadian clock. Melatonin doses early in the evening advance the clock and doses late at night delay the clock with a dead zone in between where the phase of the clock does not change., Competing Interests: Declaration of competing interest The authors affirm that we have no conflicting or competing interests that could influence this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Healthy age-related cognitive changes are highly heterogeneous across individuals. This variability is increasingly explained through the lens of spontaneous fluctuations of brain activity, now considered a powerful index of age-related changes. However, brain activity is a biological process modulated by circadian rhythms, and how these fluctuations evolve throughout the day is under investigation., Methods: We analyzed data from 101 healthy late middle-aged participants from the Cognitive Fitness in Aging study (68 women and 33 men; aged 50-69 years). Participants completed 5 electroencephalographic (EEG) recordings of spontaneous resting-state activity on the same day. We used weighted phase-lag index (wPLI) analyses as an index of the functional synchrony between brain regions couplings, and we computed daily global PLI fluctuation rates of the 5 recordings to assess the association with cognitive performance and β-amyloid and tau/neuroinflammation pathological markers., Results: We found that theta and gamma daily fluctuations in the salience-control executive internetwork (SN-CEN) are associated with distinct mechanisms underlying cognitive heterogeneity in aging. Higher levels of SN-CEN theta daily fluctuations appear to be deleterious for memory performance and were associated with higher tau/neuroinflammation rates. In contrast, higher levels of gamma daily fluctuations are positively associated with executive performance and were associated with lower rate of β-amyloid deposition., Discussion: Thus, accounting for daily EEG fluctuations of brain activity contributes to a better understanding of subtle brain changes underlying individuals' cognitive performance in healthy aging. Results also provide arguments for considering the time of day when assessing cognition for old adults in a clinical context., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Disruption of circadian rhythms contributes to deficits in cognitive functions during aging. Up to date, the biochemical, molecular and chronobiological bases of such deterioration have not been completely elucidated. Here, we aim: 1) to investigate the endogenous nature of 24 h-rhythms of antioxidant defenses, oxidative stress, clocḱ's, and neurotrophic factors expression, in the rat temporal cortex (TC), and 2) to study the consequences of aging on the circadian organization of those factors. We observed a circadian organization of antioxidant enzymes activity, lipoperoxidation and the clock, BMAL1 and RORa, proteins, in the TC of young rats. Such temporal organization suggests the existence of a two-way communication among clock transcription factors and antioxidant defenses. This might generate the rhythmic and circadian expression of Bdnf and Rc3 genes involved in the TC-depending cognitive function. Noteworthy, such circadian organization disappears in the TC of aged rats. Aging also reduces glutathione peroxidase activity and expression, and it increases lipid peroxidation, throughout a 24 h-period. An increased oxidative stress makes the cellular redox environment change into an oxidative status which alters the endogenous clock activity and disrupts the circadian organization of, at least part, of the molecular basis of the synaptic plasticity in the TC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Sleep and biological rhythms are integral to mood regulation across the lifespan, particularly in bipolar disorder (BD), where alterations in sleep phase, structure, and duration occur in all mood states. These disruptions are linked to poorer quality of life, heightened suicide risk, impaired cognitive function, and increased relapse rates. This review highlights the pathophysiology of sleep disturbances in BD and aims to consolidate understanding and clinical applications of these phenomena. It also summarizes the evolution of sleep and biological rhythms assessment methods, including ecological momentary assessment (EMA) and digital phenotyping. It underscores the importance of recognizing circadian rhythm involvement in mood regulation, suggesting potential therapeutic targets. Future research directions include elucidating circadian clock gene mechanisms, understanding environmental impacts on circadian rhythms, and investigating the bidirectional relationship between sleep disturbances and mood regulation in BD. Standardizing assessment methods and addressing privacy concerns related to EMA technology and digital phenotyping are essential for advancing research. Collaborative efforts are crucial for enhancing clinical applicability and understanding the broader implications of biological rhythms in BD diagnosis and treatment. Overall, recognizing the significance of sleep and biological rhythms in BD offers promise for improved outcomes through targeted interventions and a deeper understanding of the disorder's underlying mechanisms., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

The determination of age-related transcriptional changes may contribute to the understanding of health and life expectancy. The broad application of results from age cohorts may have limitations. Altering sample sizes per time point or sex, using a single mouse strain or tissue, a limited number of replicates, or omitting the middle of life can bias the surveys. To achieve higher general validity and to identify less distinctive players, bulk RNA sequencing of a mouse cohort, including seven organs of two strains from both sexes of 5 ages, was performed. Machine learning by bootstrapped variable importance and selection methodology (Boruta) was used to identify common aging features where the circadian rhythms (CiR) transcripts appear as promising age markers in an unsupervised analysis. Pathways of 11 numerically analyzed local network clusters were affected and classified into four major gene expression profiles, whereby CiR and proteostasis candidates were particularly conspicuous with partially opposing changes. In a data-based interaction association network, the CiR-proteostasis axis occupies an exposed central position, highlighting its relevance. The computation of 11,830 individual transcript associations provides potential superordinate contributors, such as hormones, to age-related changes, as in CiR. In hormone-sensitive LNCaP cells, short-term supraphysiologic levels of the sex hormones dihydrotestosterone or estradiol increase the expression of the CiR transcript Bhlhe40 and the associated senescence regulator Cdkn2b (p15). According to these findings, the bilateral dysregulation of CiR appears as a fundamental protagonist of aging, whose transcripts could serve as a biological marker and its restoration as a therapeutic opportunity., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)