BACKGROUND: Circadian health refers to individuals\' well-being and balance in terms of their circadian rhythm. It is influenced by external cues. In adults, a close relationship between circadian-related alterations and obesity has been described. However, studies in children are scarce, and circadian health and its association with obesity have not been evaluated globally. We aimed to assess whether circadian health differed between children with and without obesity as determined by a global circadian score (GCS) in a school-age population.
METHODS: Four hundred and thirty-two children (7-12 years) were recruited in Spain. Non-invasive tools were used to calculate the GCS: (1) 7-day rhythm of wrist temperature (T), activity (A), position (P), an integrative variable that combines T, A, and P (TAP); (2) cortisol; and (3) 7-day food and sleep records. Body mass index, body fat percentage, waist circumference (WC), melatonin concentration, and cardiometabolic marker levels were determined.
RESULTS: Circadian health, as assessed by the GCS, differed among children with obesity, overweight, and normal weight, with poorer circadian health among children with obesity. Children with obesity and abdominal obesity had 3.54 and 2.39 greater odds of having poor circadian health, respectively, than did those with normal weight or low WC. The percentage of rhythmicity, a marker of the robustness of the TAP rhythm, and the amplitude, both components of the GCS, decreased with increasing obesity. Different lifestyle behaviors were involved in the association between circadian health and obesity, particularly protein intake (P = 0.024), physical activity level (P = 0.076) and chronotype (P = 0.029).
CONCLUSIONS: The GCS can capture the relationship between circadian health and obesity in school-age children. Protein intake, physical activity level, and chronotype were involved in this association. Early intervention based on improving circadian health may help to prevent childhood obesity.

Neuropsychological studies report anxiety and depression like symptoms in patients suffering from lifestyle disorder but its impact on locomotor function lacks clarity. Our study investigates locomotor deficits resulting due to perturbations in cerebellum of high fat diet (HFD), chronodisruption (CD) or a combination (HCD) model of lifestyle disorder. Significant downregulation in levels of cerebellar clock genes (Bmal-1, Clock, Per 1 and Per 2) and Bdnf-Trkb pathway genes (Bdnf, TrkB and Syn1 levels) were recorded. Further, locomotor deficits were observed in all the three experimental groups as evidenced by actimeter test, pole test and wire hanging test. Nuclear pyknosis of Purkinje cells, their derangement and inflammation were the hallmark of cerebellar tissue of all the three experimental groups. Taken together, this study generates important links between cerebellar clock oscillations, locomotor function and Bdnf-TrkB signaling.

The origin of biological rhythms goes back to the very beginning of life. They are observed in the animal and plant world at all levels of organization, from cells to ecosystems. As early as the 18th century, plant scientists were the first to explain the relationship between flowering cycles and environmental cycles, emphasizing the importance of daily light-dark cycles and the seasons. Our temporal structure is controlled by external and internal rhythmic signals. Light is the main synchronizer of the circadian system, as daily exposure to light entrains our clock over 24 hours, the endogenous period of the circadian system being close to, but not exactly, 24 hours. In 1960, a seminal scientific meeting, the Cold Spring Harbor Symposium on Biological Rhythms, brought together all the biological rhythms scientists of the time, a number of whom are considered the founders of modern chronobiology. All aspects of biological rhythms were addressed, from the properties of circadian rhythms to their practical and ecological aspects. Birth of chronobiology dates from this period, with the definition of its vocabulary and specificities in metabolism, photoperiodism, animal physiology, etc. At around the same time, and right up to the present day, research has focused on melatonin, the circadian neurohormone of the pineal gland, with data on its pattern, metabolism, control by light and clinical applications. However, light has a double face, as it has positive effects as a circadian clock entraining agent, but also deleterious effects, as it can lead to chronodisruption when exposed chronically at night, which can increase the risk of cancer and other diseases. Finally, research over the past few decades has unraveled the anatomical location of circadian clocks and their cellular and molecular mechanisms. This recent research has in turn allowed us to explain how circadian rhythms control physiology and health.

Chronic consumption of a high-calorie diet coupled with an altered sleep-wake cycle causes disruption of circadian clock that can impact the gut microbiome leading to metabolic syndrome and associated diseases. Herein, we investigate the effects of a high fat high fructose diet (H) alone or in combination with photoperiodic shifts induced chronodisruption (CD) on gut microbiota of C57BL/6J male mice. Further, the merits of daily evening intraperitoneal administration of melatonin in restoring gut microbiota are studied herein. Experimental groups viz. H, CD and HCD mice recorded higher levels of serum pro-inflammatory cytokines (TNF-α and IL-6) and lower levels of the anti-inflammatory cytokine, IL-10. These findings correlate with a concomitant increase in the transcripts of TLR4, TNF-α, and IL-6 in small intestine of the said groups. A decrement in mRNA levels of Ocln, ZO-1 and Vdr in these groups implied towards an altered gut permeability. These results were in agreement with the observed decrement in percentage abundance of total gut microflora and Firmicutes: Bacteroidetes (F/B) ratio. Melatonin administration accounted for lower-level inflammation (serum and gut) along with an improvement in gut permeability markers. The total abundance of gut microflora and F/B ratio showed an improvement in all the melatonin-treated groups and the same is the highlight of this study. Taken together, our study is the first to report perturbations in gut microbiota resulting due to a combination of photoperiodic shifts induced CD and a high fat high calorie diet-induced lifestyle disorder. Further, melatonin-mediated rejuvenation of gut microbiome provides prima facie evidence of its role in improving gut dysbiosis that needs a detailed scrutiny.

Changes in circadian rhythms have been observed in patients with chronic kidney disease (CKD), and evidence suggests that these changes can have a negative impact on health. This study aimed to investigate the existence of hemodialysis-induced chronodisruption, the chronotype distribution, and their association with sleep quality and quality of life (QoL). This was a cross-sectional study that enrolled 165 patients (mean age: 51.1 ± 12.5 y, 60.6% male) undergoing hemodialysis from three local units. The following instruments were used: the Morning-Eveningness Questionnaire (MEQ); a modified version of the Munich Chronotype Questionnaire (MCQT) to estimate hemodialysis-induced chronodisruption (HIC); the Kidney Disease QoL Short Form (KDQOL-SF); the Epworth Sleepiness Scale (ESS); the Pittsburgh Sleep Quality Index (PSQI) and the 10-Cognitive Screener (10-CS). HIC was present in 40.6% of CKD patients. Morning chronotype was prevalent in CKD patients (69%) compared to evening-type (17.1%) and significantly different from a paired sample from the general population (p < 0.001). HIC and chronotype were associated with different domains of QoL but not with sleep quality. This study suggests that there is a HIC and that morning chronotype is associated with CKD patients undergoing hemodialysis, with implications for QoL.

The choroid plexus (ChP) in the brain ventricles has a major influence on brain homeostasis. In this study, we aimed to determine whether the circadian clock located in ChP is affected by chronodisruption caused by misalignment with the external light/dark cycle and/or inflammation. Adult mPer2Luc mice were maintained in the LD12:12 cycle or exposed to one of two models of chronic chronodisruption - constant light for 22-25 weeks (cLL) or 6-hour phase advances of the LD12:12 cycle repeated weekly for 12 weeks (cLD-shifts). Locomotor activity was monitored before the 4th ventricle ChP and suprachiasmatic nuclei (SCN) explants were recorded in real time for PER2-driven population and single-cell bioluminescence rhythms. In addition, plasma immune marker concentrations and gene expression in ChP, prefrontal cortex, hippocampus and cerebellum were analyzed. cLL dampened the SCN clock but did not shorten the inactivity interval (sleep). cLD-shifts had no effect on the SCN clock, but transiently affected sleep duration and fragmentation. Both chronodisruption protocols dampened the ChP clock. Although immune markers were elevated in plasma and hippocampus, levels in ChP were unaffected, and unlike the liver clock, the ChP clock was resistant to lipopolysaccharide treatment. Importantly, both chronodisruption protocols reduced glucocorticoid signaling in ChP. The data demonstrate the high resistance of the ChP clock to inflammation, highlighting its role in protecting the brain from neuroinflammation, and on the other hand its high sensitivity to chronodisruption. Our results provide a novel link between human lifestyle-induced chronodisruption and the impairment of ChP-dependent brain homeostasis.

The biological clock regulates the way our body works throughout the day, including releasing hormones and food intake. Disruption of the biological clock (chronodisruption) may deregulate satiety, which is strictly regulated by hormones and neurotransmitters, leading to health problems like obesity. Nowadays, using bioactive compounds as a coadjutant for several pathologies is a common practice. Phenolic compounds and short-chain fatty acids, called \"chronobiotics,\" can modulate diverse mechanisms along the body to exert beneficial effects, including satiety regulation and circadian clock resynchronization; however, the evidence of the interplay between those processes is limited. This review compiles the evidence of natural chronobiotics, mainly polyphenols and short-chain fatty acids that affect the circadian clock mechanism and process modifications in genes or proteins resulting in a signaling chain that modulates satiety hormones or hunger pathways.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risk of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria and organelle, where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

Disruptions of the light/dark cycle and unhealthy diets can promote misalignment of biological rhythms and metabolic alterations, ultimately leading to an oxidative stress condition. Grape seed proanthocyanidin extract (GSPE), which possesses antioxidant properties, has demonstrated its beneficial effects in metabolic-associated diseases and its potential role in modulating circadian disruptions. Therefore, this study aimed to assess the impact of GSPE administration on the liver oxidant system of healthy and diet-induced obese rats undergoing a sudden photoperiod shift. To this end, forty-eight photoperiod-sensitive Fischer 344/IcoCrl rats were fed either a standard (STD) or a cafeteria diet (CAF) for 6 weeks. A week before euthanizing, rats were abruptly transferred from a standard photoperiod of 12 h of light/day (L12) to either a short (6 h light/day, L6) or a long photoperiod (18 h light/day, L18) while receiving a daily oral dose of vehicle (VH) or GSPE (25 mg/kg). Alterations in body weight gain, serum and liver biochemical parameters, antioxidant gene and protein expression, and antioxidant metabolites were observed. Interestingly, GSPE partially ameliorated these effects by reducing the oxidative stress status in L6 through an increase in GPx1 expression and in hepatic antioxidant metabolites and in L18 by increasing the NRF2/KEAP1/ARE pathway, thereby showing potential in the treatment of circadian-related disorders by increasing the hepatic antioxidant response in a photoperiod-dependent manner.

That disruptions of the body\'s internal clockwork can lead to negative health consequences, including cancer, is a plausible hypothesis. Yet, despite strong mechanistic and animal support, the International Agency for Research on Cancer (IARC) experts considered epidemiological evidence as limited regarding the carcinogenicity of \"shift-work involving circadian disruption\" (2007) and \"night shift work\" (2019). We use directed acyclic graphs (DAGs) to outline a concept of circadian causes that discloses challenges when choosing appropriate exposure variables. On this basis, we propose to move beyond shift-work alone as a direct cause of disease. Instead, quantifying chronodisruption as individual doses can lead to interpretable circadian epidemiology. The hypothesis is that doses of chronodisruption cause disrupted circadian organisation by leading to desynchronization of circadian rhythms. Chronodisruption can be conceptualized as the split physiological nexus of internal and external times. Biological (or internal) night - an individual\'s intrinsically favoured sleep time window - could be the backbone of circadian epidemiology. In practice, individual doses that cause disrupted circadian organisation are derived from the intersection of time intervals of being awake and an individual\'s biological night. After numerous studies counted work shifts, chronobiology may now advance circadian epidemiology with more specific dose estimation - albeit with greater challenges in measurement (time-dependent individual data) and analysis (time-dependent confounding).