Circadian clocks regulate rhythmic biological processes in nearly every tissue, aligning physiology and behavior with the 24-h light-dark cycle. While the central circadian clock in the suprachiasmatic nucleus (SCN) has been extensively studied, emerging evidence indicates that virtually every cell in the body possesses its own locally autonomous circadian clock. This raises a fundamental question: why do multicellular organisms utilize multiple circadian clocks instead of a single master clock broadcasting time cues? Here, we examine how distributed local clocks differ from phase-resettable cycles and ensure robust temporal scheduling of physiological processes. We discuss how internal entrainment among local clocks governs self-sustained, yet flexible, circadian organization of tissue-specific responses to environmental changes. We also examine how the organization of clocks contributes to seasonal homeostasis, and the implications for disease when coordination among these clocks is disrupted.

The impact of dietary patterns on health and lifespan is well-established, yet the effects of meal timing on the aging process and risk of premature death remain unclear. This study aimed to investigate the association between the difference in energy and macronutrient intake at dinner versus breakfast and the risk of premature mortality and biological aging.

Utilizing data from the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2014, a cohort of 27,261 adults was examined. Dietary data were collected through 24-h dietary recalls, and Cox proportional hazards models and binary logistic regression models were used to assess the risk of premature death and indicators of biological aging.

Individuals with higher energy and protein intake at dinner compared to breakfast exhibited an increased risk of premature death and higher biological aging indicators. Isocaloric substitution of energy and macronutrients from breakfast to dinner significantly increased the risk of aging.

The difference in energy and macronutrient intake at dinner versus breakfast is closely associated with the risk of premature death and biological aging. The findings underscore the potential impact of meal timing on metabolic health and lifespan extension.

Circadian biology influences the gastrointestinal system as exemplified by hormonal patterns that modulate appetite. Indeed, people tend to get hungrier towards the later parts of the day. How misalignment of our circadian biology with behavioral factors (i.e. diet, exercise, sleep, etc.) influences obesity related disease has been an area of intense recent investigation.

The gastrointestinal hormones (e.g. ghrelin, glucagon-like polypeptide-1, glucose dependent insulinotrophic peptide, peptide tyrosine-tyrosine, and insulin) play unique roles across the 24-h cycle in fostering anticipatory responses that promote desires to eat while concurrently responding to environmental stimuli. A persons chronotype has emerged as a target area since it provides a metric of circadian biology interacting with environmental factors and affects all people. In fact, later chronotypes tend to be at higher risk for obesity, due to in part, alterations in gastrointestinal hormones (e.g. GIP, insulin) that align with behavioral observations of greater food intake and desires to eat fatty/sweet foods later in the day.

Changes in gastrointestinal hormones across the 24-h cycle impact obesity risk when misalignment of our circadian biology occurs with behavioral cycles. Better understanding how chronotype modulates appetite may enable personalized prescription of exercise, diet and/or medication to foster reduced chronic disease risk.

The current exploratory pilot study examined whether social rhythm regularity, as measured by a social rhythm metric, was associated with: (1) the regularity of circadian rhythms and/or sleep regularity metrics; and (2) sleep quality, affective function and alcohol use. Late adolescents (18-22 years old) who drink alcohol (n = 36; 61.1% female, Mage = 21.26 years) completed a 14-day ecological momentary assessment protocol, wore a wrist actigraph for 14 days, and completed two overnight visits (Thursday and Sunday) to assess dim light melatonin onset. Sleep regularity metrics included standard deviation, composite phase deviation, social jet lag and inter-daily stability. We used dim light melatonin onset data to calculate the stability of the circadian phase (Sunday minus Thursday). Participants completed surveys and ecological momentary assessments that assessed global and daily sleep quality, affective function, and alcohol use. Correlational analysis and robust regression modelling were used. More regular social rhythms were associated with higher regularities of mid-sleep timing based on standard deviations, but were not associated with other sleep regularity metrics or stability of the circadian phase. More regular social rhythms were associated with better sleep quality, but were not associated with affective function or alcohol use. Social rhythm regularity is a unique construct compared with existing sleep quality metrics. In contrast with the social zeitgeber hypothesis, social rhythm regularity was not associated with circadian rhythm regularity measured by dim light melatonin onset. However, social rhythm regularity may be an under-recognized contributor to better sleep quality.

There has been sharp increase in the incidence of hip fractures (HFs) with the increasing aging globally. However, it remains ambiguous regarding the association between HF risk and sleep duration. This study intended to explore the association between sleep duration and HF risk among the older adults.

The study assessed a cohort of 7,540 participants aged at least 60 years old using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010, as well as from 2013 to 2014. Two distinct groups of HF and non-HF were constructed on the basis of their history of HFs. Based on the self-reported sleep duration through a structured questionnaire, multivariate logistic regression analyses were conducted to examine the relationship between sleep duration and HF risk. In addition, restricted cubic splines (RCS) were used to assess linearity. The receiver operating characteristic (ROC) curve was used to explore the threshold of sleep duration for HF risk.

HFs were found in 129 patients among the 7,540 participants over 60 years of age with mean age of 70.17 ± 7.1 years. Significant differences in sleep duration were observed between the HF and non-HF groups (7.73 ± 1.68 h vs. 7.11 ± 1.42 h; p = 0.006). The multivariate analysis was adjusted for sociodemographic, behavioral lifestyle, and comorbidities. A 1-h increase in sleep duration was associated with higher odds of having prior hip fractures in unadjusted models [odds ratio (OR) = 1.36; 1.11, 1.67; p = 0.004], minimally adjusted models (OR = 1.23; 1.03, 1.48; p = 0.025), second adjusted models (OR = 1.22; 1.02,1.45; p = 0.026) and fully adjusted models (OR = 1.22; 1.03,1.45; p = 0.026). The relationship remained consistent across all four models, indicating the correlation of a longer sleep duration with an elevated HF risk. RCS analysis revealed a statistically linear relationship between sleep duration and HF risk (p-nonlinear = 0.244, p-overall < 0.01). In addition, the identified threshold of sleep duration linked to HF risk was determined to be 7.5 h among the older adults (AUC = 0.611).

This study suggests an linear association between sleep duration and the risk of HFs. Further research is needed to validate these findings and more clearly identify the clinical relevance of this potential relationship.

Breast cancer (BC) remains the most prevalent malignancy among women. Clinical evidence indicates that genetic variations related to circadian rhythms, as well as the timing of therapeutic interventions, influence the response to radiation therapy and the toxicity of pharmacological treatments in women with BC. This study aimed to identify key circadian rhythm-related genes (CRGs) using bioinformatics and machine learning, and construct a prognostic model to predict clinical outcomes.

Transcriptome data for BC were retrieved from The Cancer Genome Atlas database. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to develop a prognostic model based on CRGs. The predictive performance of the risk score model was evaluated. Univariate and multivariate Cox regression analyses were applied to construct the prognostic model and stratify patients into high-risk and low-risk groups. Additionally, differences in immune microenvironment, immunotherapy efficacy, and tumor mutation burden were assessed between risk groups.

A prognostic risk score model comprising 17 CRGs was developed. The areas under the receiver operating characteristic curve for overall survival at 1, 3, 5, and 7 years exceeded 0.6, indicating acceptable predictive performance. Calibration plots and decision curve analyses demonstrated the use of the model in prognostic prediction. Significant differences in immune microenvironment, immunotherapy efficacy, and tumor mutation burden were identified between the low-risk and high-risk groups.

The circadian rhythm-based gene model, effectively predicted the prognosis of individuals with BC, highlighting its potential to inform personalized therapeutic strategies and improve patient outcomes.

The circadian system maintains optimal biological functions at the appropriate time of day, and the disruption of this organization can contribute to the pathogenesis of cardiometabolic disorders. The timing of eating is a prominent external time cue that influences the circadian system. "Chrononutrition" is an emerging dimension of nutrition and active area of research that examines how timing-related aspects of eating and nutrition impact circadian rhythms, biological processes, and disease pathogenesis. There is evidence to support chrononutrition as a form of chronotherapy, such that optimizing the timing of eating may serve as an actionable strategy to improve cardiometabolic health. This report summarizes key information from the National Heart, Lung, and Blood Institute's virtual workshop entitled "Chrononutrition: Elucidating the Role of Circadian Biology and Meal Timing in Cardiometabolic Health," which convened on May 2 to 3, 2023, to review current literature and identify critical knowledge gaps and research opportunities. The speakers presented evidence highlighting the impact on cardiometabolic health of earlier and shorter eating windows and more consistent day-to-day eating patterns. The multidimensionality of chrononutrition was a common theme, as it encompasses multiple facets of eating along with the timing of other behaviors including sleep and physical activity. Advancing the emerging field of chrononutrition will require: (1) standardization of terminology and metrics; (2) scalable and precise tools for real-world settings; (3) consideration of individual differences that may act as effect modifiers; and (4) deeper understanding of social, behavioral, and cultural influences. Ultimately, there is great potential for circadian-based dietary interventions to improve cardiometabolic health.

Exercise interventions represent an effective strategy to prevent and treat metabolic diseases and the time-of-day-dependent effects of exercise on metabolic outcomes are becoming increasingly apparent. We aimed to study the influence of time-restricted wheel running on whole-body energy and glucose homeostasis. Male, 8-week-old, C57BL/6NTac mice were fed either a 60% high-fat diet (HFD) or a 10% low-fat diet (LFD) for 4 weeks. Following this, mice were given access to a running wheel between zeitgeber time (ZT) 12-16 (early dark phase) or ZT 20-0 (late dark phase). Sedentary mice had access to a permanently locked wheel. Mice were housed under these conditions in metabolic chambers for 4 weeks in which LFD and HFD conditions were maintained. Following the exercise intervention, body composition and glucose tolerance were assessed. Wheel running during either the early or late dark phase resulted in metabolic improvements such as attenuation in body weight gain, enhanced glucose tolerance and reduced ectopic lipid deposition. However, late dark phase exercise resulted in a greater reduction in body weight gain, as well as enhanced metabolic flexibility and insulin sensitivity. Our data suggest that late dark phase versus early dark phase exercise confers greater metabolic adaptations in HFD-fed mice.

Night shift work in healthcare settings is associated with increased fatigue, decreased alertness and potential risks to patient safety. While nurses napping during night shifts has been proposed as a strategy to mitigate these effects, its implementation remains controversial and understudied from a managerial perspective.

This study aimed to explore nursing and medical managers' perceptions of, and support for nurses' night shift napping policies in intensive care units.

A qualitative descriptive approach was employed from the beginning of March 2024 to the end of October 2024, utilising semi-structured interviews with 40 nursing and medical managers from various intensive care units. Participants were purposively sampled to ensure diversity in experience and department. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis.

Five main themes emerged: (1) Understanding perceptions of night shift napping, (2) perceptions of the benefits of night shift napping, (3) assessing support for night shift napping, (4) barriers and challenges of applying napping strategies and (5) developing effective implementation strategies to facilitate the successful adoption of napping policies. While most managers acknowledged the potential benefits of night shift napping, they expressed apprehension about its practical implementation, staff coverage concerns and the potential for policy abuse. Supportive managers emphasised the importance of education, structured guidelines and gradual cultural change to successfully integrate napping practices.

The findings suggest that while there is growing recognition of the potential benefits of night shift napping, significant barriers to implementation persist. The results can inform the development of evidence-based napping policies and guide strategies to address managerial concerns, ultimately improving night shift working conditions and patient care quality.

Researching the perceptions and support of nursing and medical managers for night shift napping in ICUs is relevant to clinical practice, as it can provide insights into the potential benefits, challenges and strategies for implementing such policies. These findings may ultimately improve patient safety, staff well-being and quality of care.

Physical activity supports weight regulation and metabolic health, but its timing in relation to obesity and diabetes remains unclear. We aimed to assess the diurnal timing of physical activity and its association with obesity and diabetes.

We cross-sectionally analyzed hip-worn accelerometry data from 61,116 participants aged 20-75 in the German National Cohort between 2015 and 2019. We divided physical activity into sex- and age-standardized quartiles of total morning (06:00-11:59), afternoon (12:00-17:59), evening (18:00-23:59), and nighttime (00:00-06:00) physical activity. Using multivariable logistic regression, we estimated associations of physical activity timing with obesity (BMI ≥ 30.0 kg/m2) and diabetes (self-reported or HbA1c ≥ 6.5%). We accounted for sex, age, study region, education, employment, risky alcohol use, smoking, night shift work, and sleep duration.

High afternoon (top vs. bottom quartile, OR: 0.36, 95% CI: 0.33-0.38) and evening physical activity (OR: 0.45, 95% CI: 0.42-0.48) showed lower obesity odds than high morning activity (OR: 0.71, 95% CI: 0.66-0.76), whereas nighttime activity increased obesity odds (OR: 1.58, 95% CI: 1.48-1.68). Associations were similar for diabetes, with the lowest odds for afternoon (OR: 0.47, 95% CI: 0.42-0.53), followed by evening (OR: 0.56, 95% CI: 0.50-0.62) and morning activity (OR: 0.80, 95% CI: 0.71-0.89), and higher odds for nighttime activity (OR: 1.43, 95% CI: 1.29-1.58). Findings were not modified by employment status, night shift work, and sleep duration.

Our cross-sectional findings require longitudinal corroboration but suggest afternoon and evening activity provide greater metabolic health benefits than morning activity, while nighttime activity is discouraged.

Circadian health plays an important role in overall well-being. The objective of this study was to examine whether potential indicators of circadian disruption, such as exhibiting a later chronotype or greater social jetlag, in preschool-age could predict dietary habits or BMI z-scores in an eight-year follow-up.

Our data included 210 children who participated in the DAGIS Survey in 2015-2016 (baseline, mean [SD] age: 4.69 [0.89] years) and DAGIS Next in 2023 (follow-up, age: 12.03 [0.90] years). Chronotype and social jetlag were calculated from baseline sleep measures assessed from 7-day actigraphy. Diet was assessed at follow-up with a Food Frequency Questionnaire, which evaluated the weekly consumption frequency of (1) fruits and vegetables and (2) sugary foods and drinks. BMI z-score based on Finnish growth references was calculated from height and weight measures from baseline and follow-up. Associations were analyzed with linear regression models.

Follow-up BMI z-score was predicted by both preschool-aged chronotype (β-est: 0.22 [95% CI: 0.01, 0.42] p = 0.03) and social jetlag (β-est: 0.33 [95% CI: 0.02, 0.65], p = 0.04) after covariate adjustment. No associations were observed between preschool-aged chronotype or social jetlag and preadolescent fruit and vegetable or sugary food and drink consumption.

Having a later chronotype and greater social jetlag during preschool age predicted a higher preadolescent weight outcome. Obesity prevention initiatives should include efforts to reduce the risk of circadian disruption among young children, by accounting for chronotype and aiming to reduce social jetlag in interventions.

Although the contribution of the circadian clock to metabolic regulation is widely recognized, the role of eating timing in glucose metabolism and diabetes risk remains insufficiently studied. This study aimed (i) to investigate the link between the eating timing pattern relative to individual clock and glucose homoeostasis and (ii) to explore the contribution of genetic and environmental factors to eating timing parameters.

In 92 adult twins (NCT01631123), glycaemic traits were assessed using the oral glucose tolerance test. Parameters of eating timing pattern (eating timing itself, daily calorie distribution, and eating frequency) were extracted from five-day food records. Caloric midpoint defined as the time point at which 50% of daily calories are consumed. Circadian timing of eating was determined as a time interval between the clock time of eating and a corrected midpoint of sleep, a chronotype marker. Heritability of eating timing components was estimated by comparing correlations within monozygotic and dizygotic twin pairs and fitting genetic structural equation models.

Among components of eating timing, the most associations were found for the circadian time of caloric midpoint (CCM). Later CCM was significantly associated with poorer insulin sensitivity, i.e. with lower ISI Stumvoll (β = 0.304, p = 5.9 × 10-4) and higher HOMA-IR (β = -0.258, p = 0.011) indices, as well as with higher fasting insulin levels (β = -0.259, p = 0.013), even after the model adjustment for sex, age, daily energy intake, and sleep duration. Later CCM also demonstrated robust associations with higher BMI and waist circumference. All eating timing components showed high or moderate heritability and were strongly related to individual sleep timing.

Later eating timing in relation to an individual internal clock is associated with lower insulin sensitivity. Shifting the main calorie intake to earlier circadian times may improve glucose metabolism, but genetic factors could influence the feasibility and effectiveness of eating-timing based interventions. The findings should be investigated in a larger cohort.

This work was supported by the German Research Foundation (DFG RA 3340/4-1 to OP-R, project number 530918029), by the European Association for the Study of Diabetes (Morgagni Prize 2020 to OP-R), and by the German Federal Ministry of Education and Research (BMBF NUGAT 0315424 to AFHP). The DZD is funded by the German Federal Ministry for Education and Research (01GI0925).

Circadian disruption promotes weight gain and poor health. The extent to which sex plays a role in the relationship between the circadian timing of behaviors and health outcomes in individuals with overweight/obesity is unclear.

We investigated the sex-specific associations between circadian alignment and cardiometabolic health markers in females and males with overweight/obesity.

Thirty volunteers with overweight/obesity (15 female; body mass index ≥25.1 kg/m2) underwent an evening in-laboratory assessment for dim-light melatonin onset (DLMO), body composition via dual energy x-ray absorptiometry, and a fasted blood sample. Circadian alignment was determined as the time difference between DLMO and average sleep onset over 7 days (phase angle), with participants categorized into narrow/wide phase angle groups based on median phase angle split. Due to known differences in metabolic markers between sexes, participants were subdivided based on sex into narrow and wide phase angle groups.

Males in the narrow phase angle group had higher android/gynoid body fat distribution, triglycerides, and metabolic syndrome risk scores, while females had higher overall body fat percentage, glucose, and resting heart rates (all P < .04). Furthermore, a narrower phase angle in males was negatively associated with android/gynoid body fat (r = -0.53, P = .04) and negatively associated with body fat (r = -0.62, P = .01) and heart rate (r = -0.73, P < .01) in females.

Circadian disruption may not only promote a trajectory of weight gain but could also contribute to negative health consequences in a sex-dependent manner in those already with overweight/obesity. These data may have implications for clinical utility in sex-specific sleep and circadian interventions for adults with overweight/obesity.

Greater social jetlag and late chronotypes have been linked to poor glucose metabolism, but their effects on diabetes risk in Asians remain unclear. This study investigated the prospective association between social jetlag, chronotype and diabetes risk among Japanese workers. We included 1681 workers (73% were daytime workers) aged 18-78 years who attended a nutritional survey in 2015 and 2016 and were followed for diabetes incidence until May 31, 2022. Social jetlag was defined as the absolute difference in the midpoint of sleep times between weekdays and weekends. Chronotype was estimated using the mid-sleep time on weekends that was corrected with sleep debt on weekdays. Following the American Diabetes Association criteria, diabetes onset was defined as the time when the participant first met any of the following conditions: HbA1c ≥ 6.5%, fasting plasma glucose ≥ 126 mg/dL, random plasma glucose ≥ 200 mg/dL or current use of antidiabetic medication. The Cox proportional hazards model was used to estimate hazard ratios (HRs) for diabetes incidence. Among the study participants, 88.8% were male, 5.0% experienced ≥ 2 h of social jetlag, and 7.6% were classified as having a late chronotype. During the 7-year follow-up, 107 individuals (6.4%) developed diabetes. Among daytime workers, social jetlag was not associated with diabetes risk: multivariable-adjusted HRs (95% CI) for diabetes were 1.00, 0.90 (0.52-1.55) and 1.08 (0.43-2.75) in participants with < 1.0, 1.0 to 1.9, and ≥ 2.0 h of social jetlag, respectively. Late chronotype was associated with higher diabetes risk, although not statistically significant, compared to early chronotype; multivariable-adjusted HRs (95% CI) were 1.32 (0.80-2.18) for intermediate chronotype and 1.98 (0.77-5.10) for late chronotype. In conclusion, this study suggests an association between late chronotypes and increased risk of diabetes among daytime workers and also highlights a mediating role of lifestyle-related behaviours on chronotype and their impact on metabolic health.

Most aspects of physiology and behaviour fluctuate every 24 h in mammals. These circadian rhythms are orchestrated by an autonomous central clock located in the suprachiasmatic nuclei that coordinates the timing of cellular clocks in tissues throughout the body. The critical role of this circadian system is emphasized by increasing evidence associating disruption of circadian rhythms with diverse pathologies. Accordingly, mounting evidence suggests a bidirectional relationship where disruption of rhythms by circadian misalignment may contribute to liver diseases while liver diseases alter the central clock and circadian rhythms in other tissues. Therefore, liver pathophysiology may broadly impact the circadian system and may provide a mechanistic framework for understanding and targeting metabolic diseases and adjust metabolic setpoints.

Effective countermeasures against the adverse cardiovascular effects of circadian misalignment, such as effects experienced due to night work or jet lag, remain to be established in humans. Here, we aim to test whether eating only during daytime can mitigate such adverse effects vs. eating during the night and day (typical for night shift workers) under simulated night work (secondary analysis of NCT02291952). This single-blind, parallel-arm trial randomized 20 healthy participants (non-shift workers) to simulated night work with meals consumed during night and day (Nighttime Meal Control Group) or only during daytime (Daytime Meal Intervention Group). The primary outcomes were pNN50 (percentage consecutive heartbeat intervals >50 ms), RMSSD (root mean square of successive heartbeat differences), and LF/HF (low/high cardiac frequency). The secondary outcome was blood concentrations of prothrombotic factor plasminogen activator inhibitor-1 (PAI-1). These measures were assessed under Constant Routine conditions, before (baseline) and after (postmisalignment) simulated night work. The meal timing intervention significantly modified the impact of simulated night work on cardiac vagal modulation and PAI-1 (pFDR = 0.001). In the Control Group, the postmisalignment Constant Routine showed a decrease in pNN50 by 25.7% (pFDR = 0.008) and RMMSD by 14.3% (pFDR = 0.02), and an increase in LF/HF by 5.5% (pFDR = 0.04) and PAI-1 by 23.9% (pFDR = 0.04), vs. the baseline Constant Routine. In the Intervention Group, there were no significant changes in these outcomes. For exploratory outcomes, the intervention significantly modified the impact of simulated night work on blood pressure (P < 0.05), with no significant change in the Control Group, and a significant reduction by 6-8% (P < 0.01) in the Intervention Group; without significant effects for heart rate or cortisol. These findings indicate that daytime eating, despite mistimed sleep, may mitigate changes in cardiovascular risk factors and offer translational evidence for developing a behavioral strategy to help minimize the adverse changes in cardiovascular risk factors in individuals exposed to circadian misalignment, such as shift workers.

Sleep health has recently been incorporated into the Life's Essential 8 of the American Heart Association. Little is known about the associations between changes in nighttime sleep behavior and healthy outcomes, especially for the elderly. This study explores associations between transition of nighttime sleep duration and sleep quality and cardiovascular diseases (CVD) among middle-aged and older adults in China.

Data were derived from the China Health and Retirement Longitudinal Study from 2011 to 2018, and a total of 7,905 participants age ≥ 45 years were included. Participants were classified according to nighttime sleep duration (6-8, < 6 or > 8 h) and sleep quality assessed by the number of restless sleep days in the past week (< 3, 3-7 days). Four groups of the changing patterns in nighttime sleep duration and sleep quality between 2011 and 2015 were identified. CVD including heart disease and stroke was defined based on medical diagnosis. Robust Poisson regression and the restricted cubic spline were employed to evaluate the association between the transition of nighttime sleep behavior and the risk of CVD.

Compared to participants with consistently optimal nighttime sleep duration, those with consistently non-optimal (incidence rate ratio [IRR]: 1.36, 95% confidence interval [CI]: 1.15-1.61, P < 0.001), optimal to non-optimal (IRR: 1.20, 95% CI: 1.02-1.43, P = 0.032), or non-optimal to optimal (IRR: 1.23, 95% CI: 1.02-1.48, P = 0.026) transition in nighttime sleep duration had higher risks of CVD. Additionally, those with a good to poor (IRR: 1.42, 95% CI: 1.20-1.68, P < 0.001) or a consistently poor (IRR: 1.55, 95% CI: 1.32-1.83, P < 0.001) changing pattern in nighttime sleep quality were associated with an increased risk of CVD compared to those with a consistently good changing pattern. There was a U-shaped association between changes in nighttime sleep duration and the incidence of CVD in sleep-deprived people. Changes in sleep quality and the risk of CVD exhibited a linear association.

Persistent non-optimal nighttime sleep duration and poor sleep quality are associated with an increased risk of CVD in middle-aged and older adults. These findings highlight the importance of considering transitions in sleep behavior in CVD risk assessment for middle-aged and older adults, and emphasize the significance of long-term exposure to poor sleep behavior on their cardiovascular health.

Circadian disruption is pervasive in modern society and associated with increased risk of disease. Chronic jet lag paradigms are popular experimental tools aiming to emulate human circadian disruption experienced during rotating and night shift work. Chronic jet lag induces metabolic phenotypes tied to liver and systemic functions, yet lack of a clear definition for how rhythmic physiology is impaired under these conditions hinders the ability to identify the underlying molecular mechanisms. Here, we compared 2 common chronic jet lag paradigms and found that neither induced arrythmicity of the liver and each had distinct effects on rhythmicity. Instead, more frequent 8-h forward shifts of the light schedule induced more severe misalignment and non-fasted hyperglycemia. Every other day shifts eventually uncoupled behavioral and hepatic rhythms from the light cycle, reminiscent of free-running conditions. These results point to misalignment, not arrhythmicity, as the initial disturbance tied to metabolic dysfunction in environmental circadian disruption and highlight considerations for the interpretation and design of chronic jet lag studies.

Sleep timing, influenced by chronotype, behavior, and circadian rhythms, is critical for human health. While previous research has linked chronotype to various health outcomes, the impact of aligning sleep timing with chronotype on physical health remains underexplored. The objective of this study is to investigate the association between chronotype, actual sleep timing, and their alignment with a spectrum of physical health outcomes.

Objective sleep timing (actigraphy, categorized as early, intermediate, or late) and chronotype (self-reported, categorized as morning, intermediate, or evening types) were derived from the UK Biobank (n=73,888 middle-aged and older adults) and used in cross-sectional and longitudinal analyses. Physical health outcomes included metabolic disorders, diabetes, obesity, hypertension, circulatory disorders, digestive disorders, respiratory disorders, and all-cause cancer based on ICD10 codes. Analyses were adjusted for demographic factors, sleep duration and sleep timing stability.

As compared to morning types with early behavior (aligned), morning types with late behavior (misaligned) had an increased risk of all included physical health disorders (p's<0.001). As compared to evening-types with late behavior (aligned), however, evening-types with early behavior (misaligned) had a decreased risk of diabetes, obesity, hypertension, circulatory disorders, and respiratory disorders (p < 0.01). Longitudinal analyses, in which the likelihood of developing de novo physical health disorders was associated with chronotype, behavioral timing, and alignment between the two, confirmed cross-sectional findings.

Late sleep timing across chronotypes was consistently associated with adverse physical health outcomes. These findings underscore the importance of going to sleep early, regardless of preference.

Maintaining homeostasis is essential for continued health, and the progressive decay of homeostatic processes is a hallmark of ageing. Daily environmental rhythms threaten homeostasis, and circadian clocks have evolved to execute physiological processes in a manner that anticipates, and thus mitigates, their effects on the organism. Clocks are active in almost all cell types; their rhythmicity and functional output are determined by a combination of tissue-intrinsic and systemic inputs. Numerous inputs for a specific tissue are produced by the activity of circadian clocks of other tissues or cell types, generating a form of crosstalk known as clock communication. In mammals, the central clock in the hypothalamus integrates signals from external light-dark cycles to align peripheral clocks elsewhere in the body. This regulation is complemented by a tissue-specific milieu of external, systemic and niche inputs that modulate and cooperate with the cellular circadian clock machinery of a tissue to tailor its functional output. These mechanisms of clock communication decay during ageing, and growing evidence suggests that this decline might drive ageing-related morbidities. Dietary, behavioural and pharmacological interventions may offer the possibility to overcome these changes and in turn improve healthspan.

Owing to coronavirus disease 2019 (COVID-19), the shift from offline to online classes has caused significant changes in high school students' daily habits, including sleep patterns and dietary intake. This study explored the association between sleep schedule fluctuations and dietary quality among high school girls during the COVID-19 pandemic. This study examined the association between bedtime, wake-up time, and adolescent dietary quality during the weekly online/offline school period among 517 high school girls in Incheon, South Korea.

The participants were divided into 2 groups: normal sleepers (n = 244), who maintained normal sleep schedules defined as a midpoint between bedtime and wake-up time before 5:30 a.m., during in-person and online classes; and late sleepers (n = 273), who maintained a normal sleep schedule during in-person classes but exhibited late sleep patterns defined as a midpoint after 5:30 a.m., during online classes.

Shorter sleep duration was characteristic of late sleepers with circadian rhythm disruption, who also displayed poorer dietary quality, including higher consumption of caffeinated beverages and street food and never consuming breakfast. Among the 5 constituent factors, disrupted sleep timing was associated with lower Nutrition Quotient for Adolescents scores in total, moderation, and environment. This association persisted independent of the grade level, even after adjusting for school grade. These findings highlight the significant effect of sleep patterns on dietary habits.

This study highlights the significant relationship between disrupted circadian rhythms and poor dietary quality among high-school girls. These findings reveal the need for interventions to promote healthy sleep patterns as a strategy to improve the dietary quality and overall health of adolescents.

Shift work causes a disruption between the circadian system and the external light-dark cycle, but also a misalignment between various levels of the circadian system. There is no information on patients with adrenal insufficiency (AI) who are working shifts. The objective of the study was to analyze the hormone replacement therapy with hydrocortisone (HC) and the adaptation scheme in patients with AI on shifts. Patients working on shifts (n=15) from two German endocrine centers received a questionnaire regarding their therapy scheme, dose adaptations, working shifts, dose adaptations during working shifts, and occurrence of adrenal crisis. We observed that 20% of patients stated that they experience difficulties taking glucocorticoid replacement on time, 40% of patients reported these difficulties to occur only occasionally. Consequently, nearly half of the patients had forgotten to take their replacement therapy at some point. More than 50% of patients reported an adrenal crisis during the last two years. The timely adaptation of HC or of modified-release HC during shifts was very inhomogeneous. In conclusion, the adaptation schemes for HC dosing during shift work are currently not evidence-based but opinion-driven. Our findings highlight the need for further investigations of shift workers with AI.

Chronotype indicates a person's "circadian preference," that is, the time of day when they prefer to perform certain activities (e.g. a "morning" vs "evening" person). Sleep timing is related to chronotype but is also constrained by social requirements. When sleep timing does not align with chronotype, circadian disruption can occur, and circadian disruption impairs cardiometabolic health. There are well-known racial disparities in cardiometabolic health whereby Black adults are at higher risk. It is not well-known, however, whether sleep timing within each chronotype varies between Black and White adults, which was the focus of these analyses. These data are from a cross-sectional sleep study conducted in 2020 to 2023 as an ancillary to the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study, in the United States. The Morningness-Eveningness Questionnaire (MEQ) captured chronotype in 2,373 participants aged 52-70 years. Chronotype was based on both overall MEQ score and question 19 categories. A subset of participants wore a wrist actigraphy monitor for ~7 days to assess sleep timing (n = 720). Our sample included 27% Black women, 17% Black men, 33% White women, and 24% White men. Mean MEQ score and chronotype distribution did not differ among race-gender groups. Among morning types, Black women and men had a later sleep start and midpoint than White women (23-34 minutes later for Black women, 32-53 minutes for Black men). Among intermediate types, Black women had significantly later sleep start (55 minutes later) and midpoint (44 minutes later), and Black men had a later sleep start (50 minutes later) than White women adjusting for age and study site. In summary, regardless of chronotype, Black adults had later sleep timing than White adults.

Disruptions of circadian rhythms are widespread in modern society and lead to accelerated and worsened symptoms of metabolic syndrome. In healthy mice, the circadian clock factor BMAL1 is required for skeletal muscle function and metabolism. However, the importance of muscle BMAL1 in the development of metabolic diseases, such as diet-induced obesity (DIO), remains unclear. Here, we demonstrate that skeletal muscle-specific BMAL1-deficient mice exhibit worsened glucose tolerance upon high-fat diet feeding, despite no evidence of increased weight gain. Metabolite profiling from Bmal1-deficient muscles revealed impaired glucose utilization specifically at early steps in glycolysis that dictate the switch between anabolic and catabolic glucose fate. We provide evidence that this is due to abnormal control of the nutrient stress-responsive hypoxia-inducible factor (HIF) pathway. Genetic HIF1α stabilization in muscle Bmal1-deficient mice restores glucose tolerance and expression of 217/736 dysregulated genes during DIO, including glycolytic enzymes. Together, these data indicate that during DIO, skeletal muscle BMAL1 is an important regulator of HIF-driven glycolysis and metabolic flexibility, which influences the development of high-fat-diet-induced glucose intolerance.

Sleep irregularity is increasingly recognized as a modifiable factor for cardiovascular health. This study aims to investigate relationships between short- and long-term sleep irregularity with blood pressure (BP) dynamics among older adults.

We used data from a prospective cohort involving community-dwelling older adults based on a mobile health (mHealth) app from 2018 to 2022. Short-term exposure was defined as sleep irregularity for one week. Cumulative sleep irregularity, calculated as the area under the curve over 12 months, was regarded as long-term exposure. Outcomes included short-term deviations in BP, longitudinal changes in BP, and cumulative BP over one year. Linear mixed models and generalized additive mixed models were conducted to investigate the associations between sleep irregularity and BP.

A total of 1611 participants with a median age of 73.0 years were included. Short-term and long-term cumulative sleep irregularities were associated with increased SBP, DBP, and global BP Z-score. For instance, each SD increment in cumulative sleep onset timing SD was associated with a 0.42 mmHg increase in SBP (95 % CI, 0.25 to 0.60), a 0.31 mmHg increase in DBP (95 % CI, 0.17 to 0.45), respectively. Subgroup analyses indicated stronger associations among males and those with normotension. Strong linear dose-response relationships were further observed between cumulative sleep irregularity and cumulative BP.

Sleep irregularity, in both short-term and long-term exposure, is a risk factor for poor blood pressure control among older adults, highlighting the importance of implementing interventions promoting healthy sleep habits to mitigate cardiovascular risks.

The circadian clock is a transcriptional-translational feedback loop which oscillates in virtually all nucleated cells of the body. In the decades since its discovery, it has become evident that the molecular clockwork is inextricably linked to energy metabolism. Given the frequency with which metabolic dysfunction and clock disruption co-occur, understanding why and how clock and metabolic processes are reciprocally coupled will have important implications for supporting human health and wellbeing. Here, we discuss the relevance of molecular clock function in metabolic tissues and explore its role not only as a driver of day-night variation in gene expression, but as a key mechanism for maintaining metabolic homeostasis in the face of fluctuating energy supply and demand.

Artificial light at night (ALAN) is a growing environmental issue associated with negative health outcomes. Yet, there is a dearth of evidence concerning its effect on blood pressure (BP), especially in Ghana. This study examined the associations between ALAN, blood pressure, and hypertension. The study used data from 13,784 participants in the 2014 Ghana Demographic and Health Survey (GDHS). VIIRS Nighttime Day/Night Band dataset within the Google Earth was used to assess ALAN. Data on BP were obtained from the 2014 GDHS. Linear and logistic mixed effects models were used to analyze the data. Findings showed that higher ALAN score was associated with higher systolic blood pressure (SBP), diastolic blood pressure (DBP), and higher odds of hypertension. We observed higher percentages of SBP, DBP, and hypertension among the majority ethnic populations compared to the minority. Public health interventions should aim to reduce ALAN exposure to benefit human health.

Overweight and obesity are linked to mitochondrial alterations, impaired glucose tolerance and a high risk of type 2 diabetes. Time-restricted eating (TRE) may aid in facilitating weight loss to prevent diabetes. Here, we investigated if TRE in individuals with overweight and prediabetes or obesity affects mitochondrial bioenergetics of peripheral blood mononuclear cells (PBMCs) and platelets using the Seahorse extracellular flux technology. In a 3-month randomized controlled trial, PBMCs/platelets were analyzed from 52 participants before and after a TRE intervention with a 10-h eating window or habitual living. PBMC and platelet respiratory function was evaluated through sequential addition of substrates, uncouplers, and inhibitors in living cells. After 3 months, there were no statistically significant differences in mitochondrial respiration within or between the TRE and control groups. Association analyses between PBMC/platelet respiration and clinical parameters including body mass index and fat mass showed no significant effects. In conclusion, 3 months of 10-h TRE does not alter the mitochondrial bioenergetics of PBMCs and platelets in individuals with high risk of type 2 diabetes.

Lighting interventions can mitigate fatigue by promoting circadian rhythmicity. We test whether individualized, wearable-based lighting interventions delivered via a mobile app reduce cancer-related fatigue in a randomized controlled trial with 138 breast cancer, prostate cancer, and hematopoietic stem cell transplant patients. Participants are randomized to tailored lighting intervention or control. The primary endpoint is PROMIS fatigue 4a at trial end, with secondary endpoints including change in daily fatigue, sleep, anxiety, depression, physical function, and overall health. Fatigue T-scores at week 11 do not differ between groups but decrease significantly from week 1 to week 11 (3.07 points, p = 0.001) in the intervention group, with a significant final-week treatment effect (p = 0.014). Daily fatigue, anxiety, sleep disturbance, and physical function improve within intervention. Further studies are needed to see if these results generalize in broader cancer care. The trial is registered at ClinicalTrials.gov (trial registration number: NCT04827446).

Host circadian signaling, feeding, and the gut microbiome are tightly interconnected. Changes in the gut microbial community can affect the expression of core clock genes, but the specific metabolites and molecular mechanisms that mediate this relationship remain largely unknown. Here, we sought to identify gut microbial metabolites that impact circadian signaling. Through a phenotypic screen of a focused library of gut microbial metabolites, we identified a bile acid metabolite, lithocholic acid (LCA), as a circadian modulator. LCA lengthened the circadian period of core clock gene hPer2 transcription in a dose-responsive manner in human colonic cells. We found evidence that LCA modulates the casein kinase 1 δ/ε (CK1δ/ε)-protein phosphatase 1 (PP1) feedback loop and stabilizes core clock protein cryptochrome 2 (CRY2). Furthermore, we showed that LCA feeding alters circadian transcription in mouse distal ileum and colon. Taken together, our work identifies LCA as a molecular link between host circadian biology and the microbiome. Because bile acids are secreted in response to feeding, our work provides potential mechanistic insight into the molecular nature of the food-entrainable oscillator by which peripheral clocks adapt to the timing of food intake. Given the association between circadian rhythm, feeding, and metabolic disease, our insights may offer a new avenue for modulating host health.

Lung cancer is a malignant tumor with a high morbidity and mortality rate worldwide, causing an increasing disease burden. Of these, the most common type is non-small cell lung cancer (NSCLC), which accounts for 80-85% of all lung cancer cases. Genetic research is crucial for continuously discovering susceptibility genes related to lung cancer for in-depth study. The role of genetic predisposition in the development of NSCLC, particularly within circadian rhythm pathways known to govern various physiological processes, is increasingly acknowledged. Yet, the association between genetic variants of circadian rhythm-related genes and NSCLC susceptibility among Chinese populations is not fully understood. This study carried out a two-phase (discovery and validation stages) research design to identify genetic variants associated with NSCLC risk within the circadian rhythm pathway. We employed extensive whole-genome sequencing (WGS) for 1,104 NSCLC cases and 9,635 controls. FastGWA-GLMM was used for single-locus risk association analysis of NSCLC, and we screened candidate SNPs in the validation set that comprised 4,444 cases and 174,282 controls from the Biobank Japan Project (BBJ). Furthermore, GCTA-COJO conditional analysis was utilized to confirm SNPs related to NSCLC risk. Finally, potential genetic variations that may regulate gene expression were explored in GTEx and QTLbase. RNA sequencing data were utilized for transcriptomic verification. Our study identified eight candidate SNPs associated with NSCLC susceptibility within the circadian rhythm pathway that met the requirement with P < 0.05 in both the discovery and validation populations. After conditional analysis, five of these SNPs remained. The A allele of CUL1 rs78524436 (ORmeta = 1.18, 95%CI: 1.09-1.29, Pmeta = 7.99e-5) and the A allele of TEF rs9611588 (ORmeta = 1.06, 95%CI: 1.02-1.10, Pmeta = 1.28e-3) were associated with an increased risk of NSCLC. The A allele of FBXL21 rs2069868 (ORmeta = 0.86, 95%CI: 0.80-0.96, Pmeta = 4.78e-4), the T allele of CSNK1D rs147316973 (ORmeta = 0.76, 95%CI: 0.65-0.88, Pmeta = 5.93e-4), and the A allele of RORA rs1589701 (ORmeta = 0.94, 95%CI: 0.91-0.98, Pmeta = 3.40e-3) were associated with a lower risk of NSCLC, separately. The eQTL results revealed an association between RORA rs1589701 and TEF rs9611588 with the expression levels of RORA and TEF, respectively. Transcriptome data indicated that RORA and TEF showed lower expression levels in tumor tissues compared to normal tissues (P < 0.001). Moreover, poorer survival was observed in patients with lower RORA and TEF expressions (log-rank P < 0.05). Our findings spotlight potential susceptibility loci within circadian rhythm pathway genes that modulate NSCLC carcinogenesis, which enriches the understanding of the genetic susceptibility of NSCLC in the Chinese population and provides a more solid basis for exploring the biological mechanism of circadian rhythm genes in NSCLC.

Ergothioneine has antioxidant, anti-inflammatory, and cell-protective properties. Circadian rhythm disruption can lead to health issues, such as insomnia, mental illness, chronic diseases, and cancer. However, the impact of ergothioneine, as an antioxidant, on oxidative DNA damage and immune variations caused by circadian rhythm disruptions remains unclear. To investigate the effect of ergothioneine on oxidative DNA damage and immune responses caused by circadian rhythm disruption, 8-week-old mice were subjected to night time feeding and exercise restrictions for 14 days. Body weight, daytime running wheel activity, and anxiety-like behavior showed no significant differences between the night-restricted groups, regardless of ergothioneine administration. Serum interleukin-6 levels, 8-hydroxy-2'-deoxyguanosine levels in urine and nuclear DNA of the liver, testes, lungs, and pancreas were significantly reduced in the night-restricted group receiving ergothioneine compared with that of the group without ergothioneine, with no significant differences observed when compared to the control group. Ergothioneine can mitigate immune function changes and oxidative DNA damage induced by circadian rhythm disruption caused by abnormal dietary timing in mice. However, it did not alleviate obesity or mental state dysregulation. These findings have important implications for improving night-shift workers health and developing therapies for diseases associated with circadian rhythm disturbances.

Maintaining the normal biological rhythms of livestock is of great significance for reflecting the environmental suitability and welfare level of animals. Mistimed feeding can interfere with the circadian rhythms of both humans and animals, resulting in disorders of lipid metabolism, obesity, and metabolic syndrome. Low-temperature environment stimulates increased appetite and decreased physical activity, resulting in higher energy intake than consumption and thus facilitating fat deposition and even obesity. In this study, growing rabbits were randomly allocated to the daytime feeding (DF) group and nighttime restricted feeding (NRF) group. Our research demonstrated that, during winter, the DF regimen disrupted the behavioral rhythms of rabbits and accelerated weight gain without changing overall feed intake. The underlying reason was that DF disturbed the lipid metabolism rhythms, promoted hepatic lipid synthesis regulated by DGAT1 and lipid synthesis of adipose tissues regulated by GPAM, thus triggering fat deposition. In contrast, the NRF regimen enhanced thermogenesis regulated by T3 and elevated body temperature and facilitated ketogenesis mediated by HMGCS2, increasing energy consumption. However, it had no significant impact on the fat content within muscle. This study offers a theoretical foundation for the refinement of feeding management and healthy raising of rabbits.

The circadian rhythm of cortisol, a key hormone essential for maintaining metabolic balance and stress homeostasis, is profoundly disrupted by night-shift work. This narrative review examines the physiological mechanisms underlying cortisol regulation, the effects of shift work on its circadian rhythm, the associated health risks, and potential mitigation strategies. Night-shift work alters the natural secretion pattern of cortisol, leading to dysregulation of the hypothalamic-pituitary-adrenal axis, which in turn can contribute to metabolic disorders, cardiovascular diseases, and impaired cognitive function. Understanding the physiological pathways mediating these changes is crucial for developing targeted interventions to mitigate the adverse effects of circadian misalignment. Potential strategies, such as controlled light exposure, strategic napping, and personalized scheduling, may help to stabilize cortisol rhythms and improve health outcomes. This review aims to provide insights that can guide future research and inform occupational health policies for night-shift workers by addressing these challenges.

Recent studies indicate that shift work may affect workers' eating habits and overall well-being. This study aimed to assess differences in eating patterns, sleep quality, and mental health between Italian shift and non-shift workers, with a focus on individual chronotype and the type of shift work (day vs. night shift).

The cross-sectional study involved 322 subjects (166 shift and 156 non-shift workers). Eating habits were evaluated using a 7-day diary and the Medi-Lite questionnaire. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and mental health with the Depression Anxiety Stress Scales (DASS). Individual chronotype was defined using the Morningness-Eveningness Questionnaire.

No significant differences in daily energy, macronutrient, and micronutrient intake between the two groups, nor in the temporal pattern of eating. However, shift workers had significantly (p < 0.05) lower adherence to the Mediterranean diet (MD) (7.6 ± 2.3 vs 8.1 ± 2.2) compared to non-shift workers. Shift workers also reported significantly poorer sleep quality (mean PSQI score 7.6 ± 3.7 vs. 5.8 ± 3.0) and higher levels of anxiety and stress symptoms. Among shift workers, those with an evening chronotype had significantly lower MD adherence than those with a morning chronotypes. Additionally, night shift workers experienced more sleep disturbances compared to day ones.

Shift workers reported lower MD adherence, poorer sleep quality, and a higher prevalence of anxiety and stress symptoms compared to a similar group of non-shift workers. Evening chronotypes and night shift work were associated with worse eating habits and sleep quality.