Reduced exposure to daytime sunlight and increased exposure to electrical lighting at night leads to late circadian and sleep timing 1–3. We have previously shown that exposure to a natural summer ...14 hr 40 min:9 hr 20 min light-dark cycle entrains the human circadian clock to solar time, such that the internal biological night begins near sunset and ends near sunrise 1. Here we show that the beginning of the biological night and sleep occur earlier after a week’s exposure to a natural winter 9 hr 20 min:14 hr 40 min light-dark cycle as compared to the modern electrical lighting environment. Further, we find that the human circadian clock is sensitive to seasonal changes in the natural light-dark cycle, showing an expansion of the biological night in winter compared to summer, akin to that seen in non-humans 4–8. We also show that circadian and sleep timing occur earlier after spending a weekend camping in a summer 14 hr 39 min:9 hr 21 min natural light-dark cycle compared to a typical weekend in the modern environment. Weekend exposure to natural light was sufficient to achieve ∼69% of the shift in circadian timing we previously reported after a week’s exposure to natural light 1. These findings provide evidence that the human circadian clock adapts to seasonal changes in the natural light-dark cycle and is timed later in the modern environment in both winter and summer. Further, we demonstrate that earlier circadian timing can be rapidly achieved through natural light exposure during a weekend spent camping.
•Living in the modern electrical lighting environment delays the human circadian clock•The human circadian clock adapts to seasonal changes in the natural light-dark cycle•A weekend camping trip prevented the typical weekend circadian and sleep delay
Late sleep timing is associated with health problems. Stothard et al. show that the human circadian clock is timed later in modern society, especially after the weekend, compared to natural light-dark cycles. Further, the clock responds to seasonal natural light-dark cycle changes and is rapidly shifted earlier by weekend camping.
Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive ...impairment, and accidents 1–7. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)—a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar 8 levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration.
•Short sleep and associated circadian misalignment reduces insulin sensitivity•Reduced insulin sensitivity was compensated by increased insulin secretion•3 days adequate sleep restored oral glucose insulin sensitivity to baseline•Circadian timing of food intake during sleep loss may elevate diabetes risk
Short sleep duration is associated with elevated diabetes risk. Eckel et al. provide evidence showing short sleep results in morning wakefulness during the biological night (i.e., circadian misalignment). Such circadian misalignment was associated with lower insulin sensitivity, indicating a novel way by which short sleep may elevate diabetes risk.
Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated ...by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake–sleep/food intake–fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.
Automated analysis of MRI data of the subregions of the hippocampus requires computational atlases built at a higher resolution than those that are typically used in current neuroimaging studies. ...Here we describe the construction of a statistical atlas of the hippocampal formation at the subregion level using ultra-high resolution, ex vivo MRI. Fifteen autopsy samples were scanned at 0.13mm isotropic resolution (on average) using customized hardware. The images were manually segmented into 13 different hippocampal substructures using a protocol specifically designed for this study; precise delineations were made possible by the extraordinary resolution of the scans. In addition to the subregions, manual annotations for neighboring structures (e.g., amygdala, cortex) were obtained from a separate dataset of in vivo, T1-weighted MRI scans of the whole brain (1mm resolution). The manual labels from the in vivo and ex vivo data were combined into a single computational atlas of the hippocampal formation with a novel atlas building algorithm based on Bayesian inference. The resulting atlas can be used to automatically segment the hippocampal subregions in structural MRI images, using an algorithm that can analyze multimodal data and adapt to variations in MRI contrast due to differences in acquisition hardware or pulse sequences. The applicability of the atlas, which we are releasing as part of FreeSurfer (version 6.0), is demonstrated with experiments on three different publicly available datasets with different types of MRI contrast. The results show that the atlas and companion segmentation method: 1) can segment T1 and T2 images, as well as their combination, 2) replicate findings on mild cognitive impairment based on high-resolution T2 data, and 3) can discriminate between Alzheimer's disease subjects and elderly controls with 88% accuracy in standard resolution (1mm) T1 data, significantly outperforming the atlas in FreeSurfer version 5.3 (86% accuracy) and classification based on whole hippocampal volume (82% accuracy).
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•A highly detailed computational atlas of the human hippocampus built upon ex vivo MRI.•Volumes of hippocampal subregions agree well with prior histological studies.•Application to Bayesian segmentation of hippocampal subregions from in vivo MRI•The segmentation method is adaptive to MRI contrast and resolution.•The atlas and segmentation code will be released as part of FreeSurfer 6.0.
Sleep health has multiple dimensions including duration, regularity, timing, and quality 1–4. The Coronavirus 2019 (COVID-19) outbreak led to Stay-at-Home orders and Social Distancing Requirements in ...countries throughout the world to limit the spread of COVID-19. We investigated sleep behaviors prior to and during Stay-at-Home orders in 139 university students (aged 22.2 ± 1.7 years old ±SD) while respectively taking the same classes in-person and remotely. During Stay-at-Home, nightly time in bed devoted to sleep (TIB, a proxy for sleep duration with regard to public health recommendations 5) increased by ∼30 min during weekdays and by ∼24 mins on weekends and regularity of sleep timing improved by ∼12 min. Sleep timing became later by ∼50 min during weekdays and ∼25 min on weekends, and thus the difference between weekend and weekday sleep timing decreased — hence reducing the amount of social jetlag 6,7. Further, we find individual differences in the change of TIB devoted to sleep such that students with shorter TIB at baseline before the first COVID-19 cases emerged locally had larger increases in weekday and weekend TIB during Stay-at-Home. The percentage of participants that reported 7 h or more sleep per night, the minimum recommended sleep duration for adults to maintain health 5 — including immune health — increased from 84% to 92% for weekdays during Stay-at-Home versus baseline. Understanding the factors underlying such changes in sleep health behaviors could help inform public health recommendations with the goal of improving sleep health during and following the Stay-at-Home orders of the COVID-19 pandemic.
Wright et al. follow the sleeping habits of college students before and during the Covid-19 lockdown, finding that the timing of sleep changed, reducing social jetlag. In addition, the regularity of sleep increased, as did total sleep duration, suggesting life during the pandemic may suggest ways to improve sleep health.
People commonly increase sleep duration on the weekend to recover from sleep loss incurred during the workweek. Whether ad libitum weekend recovery sleep prevents metabolic dysregulation caused by ...recurrent insufficient sleep is unknown. Here, we assessed sleep, circadian timing, energy intake, weight gain, and insulin sensitivity during sustained insufficient sleep (9 nights) and during recurrent insufficient sleep following ad libitum weekend recovery sleep. Healthy, young adults were randomly assigned to one of three groups: (1) control (CON; 9-h sleep opportunities, n = 8), (2) sleep restriction without weekend recovery sleep (SR; 5-h sleep opportunities, n = 14), and (3) sleep restriction with weekend recovery sleep (WR; insufficient sleep for 5-day workweek, then 2 days of weekend recovery, then 2 nights of insufficient sleep, n = 14). For SR and WR groups, insufficient sleep increased after-dinner energy intake and body weight versus baseline. During ad libitum weekend recovery sleep, participants cumulatively slept ∼1.1 h more than baseline, and after-dinner energy intake decreased versus insufficient sleep. However, during recurrent insufficient sleep following the weekend, the circadian phase was delayed, and after-dinner energy intake and body weight increased versus baseline. In SR, whole-body insulin sensitivity decreased ∼13% during insufficient sleep versus baseline, and in WR, whole-body, hepatic, and muscle insulin sensitivity decreased ∼9%–27% during recurrent insufficient sleep versus baseline. Furthermore, during the weekend, total sleep duration was lower in women versus men, and energy intake decreased to baseline levels in women but not in men. Our findings suggest that weekend recovery sleep is not an effective strategy to prevent metabolic dysregulation associated with recurrent insufficient sleep.
•Sleep loss increased after-dinner energy intake and reduced insulin sensitivity•In total, participants slept an extra 1.1 h during weekend recovery versus baseline•After-dinner energy intake was reduced during weekend recovery sleep•Weekend recovery sleep did not prevent weight gain or reduced insulin sensitivity
Weekend recovery sleep is a common sleep-loss countermeasure. Depner et al. show that short sleep led to later timing of energy intake, weight gain, and reduced insulin sensitivity. Weekend recovery sleep failed to prevent later timing of energy intake, weight gain, or reduced insulin sensitivity during recurrent short sleep following the weekend.
Caffeine's wakefulness-promoting and sleep-disrupting effects are well established, yet whether caffeine affects human circadian timing is unknown. We show that evening caffeine consumption delays ...the human circadian melatonin rhythm in vivo and that chronic application of caffeine lengthens the circadian period of molecular oscillations in vitro, primarily with an adenosine receptor/cyclic adenosine monophosphate (AMP)-dependent mechanism. In a double-blind, placebo-controlled, ~49-day long, within-subject study, we found that consumption of a caffeine dose equivalent to that in a double espresso 3 hours before habitual bedtime induced a ~40-min phase delay of the circadian melatonin rhythm in humans. This magnitude of delay was nearly half of the magnitude of the phase-delaying response induced by exposure to 3 hours of evening bright light (~3000 lux, ~7 W/m(2)) that began at habitual bedtime. Furthermore, using human osteosarcoma U2OS cells expressing clock gene luciferase reporters, we found a dose-dependent lengthening of the circadian period by caffeine. By pharmacological dissection and small interfering RNA knockdown, we established that perturbation of adenosine receptor signaling, but not ryanodine receptor or phosphodiesterase activity, was sufficient to account for caffeine's effects on cellular timekeeping. We also used a cyclic AMP biosensor to show that caffeine increased cyclic AMP levels, indicating that caffeine influenced a core component of the cellular circadian clock. Together, our findings demonstrate that caffeine influences human circadian timing, showing one way that the world's most widely consumed psychoactive drug affects human physiology.
Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia ...with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome, and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance, and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed.
Layered double hydroxides (LDHs) are important materials in the field of catalyst supports, and their surface hydroxyl functionality makes them interesting candidates for supporting well-defined ...single-site catalysts. Here, we report that the surface hydroxyl concentration can be controlled by thermal treatment of these materials under vacuum, leading to hydroxyl numbers (αOH) similar to those of dehydroxylated silica, alumina, and magnesium hydroxide. Thermal treatment of Mg0.74Al0.26(OH)2(SO4)0.1(CO3)0.03·0.62(H2O)·0.04(acetone) prepared by the aqueous miscible organic solvent treatment method (Mg2.84Al-SO4-A AMO-LDH) is shown to yield a mixed metal oxide above 300 °C by a combination of thermogravimetric analysis, powder X-ray diffraction (PXRD), BET surface area analysis, and FTIR spectroscopy. PXRD shows the disappearance of the characteristic LDH 00l peaks at 300 °C indicative of decomposition to the layered structure, coupled with a large increase in the BET surface area (95 vs 158 m2 g–1 from treatment at 275 and 300 °C, respectively). Titration of the surface hydroxyls with Mg(CH2Ph)2(THF)2 indicates that the hydroxyl number is independent of surface area for a given treatment temperature. Treatment at 450 °C under vacuum produces a mixed metal oxide material with a surface hydroxyl concentration (αOH) of 2.14 OH nm–2 similar to the hydroxyl number (αOH) of 1.80 OH nm–2 for a sample of SiO2 dehydroxylated at 500 °C. These materials appear to be suitable candidates for use as single-site organometallic catalyst supports.