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1. Predicting circadian phase in community‐dwelling later‐life adults using actigraphy data

   https://doi.org/10.1111/jsr.14425  

   Mayer, Caleb; Kim, Dae Wook; Zhang, Meina; Lee, Minki P; Forger, Daniel B; Burgess, Helen J; Moon, Chooza (August 2025, Journal of Sleep Research)

   Summary The accurate estimation of circadian phase in the real‐world has a variety of applications, including chronotherapeutic drug delivery, reduction of fatigue, and optimal jet lag or shift work scheduling. Recent work has developed and adapted algorithms to predict time‐consuming and costly laboratory circadian phase measurements using mathematical models with actigraphy or other wearable data. Here, we validate and extend these results in a home‐based cohort of later‐life adults, ranging in age from 58 to 86 years. Analysis of this population serves as a valuable extension to our understanding of phase prediction, since key features of circadian timekeeping (including circadian amplitude, response to light stimuli, and susceptibility to circadian misalignment) may become altered in older populations and when observed in real‐life settings. We assessed the ability of four models to predict ground truth dim light melatonin onset, and found that all the models could generate predictions with mean absolute errors of approximately 1.4 h or below using actigraph activity data. Simulations of the model with activity performed as well or better than the light‐based modelling predictions, validating previous findings in this novel cohort. Interestingly, the models performed comparably to actigraph‐derived sleep metrics, with the higher‐order and nonphotic activity‐based models in particular demonstrating superior performance. This work provides evidence that circadian rhythms can be reasonably estimated in later‐life adults living in home settings through mathematical modelling of data from wearable devices. 

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2. Optimal adjustment of the human circadian clock in the real world

   https://doi.org/10.1371/journal.pcbi.1008445  

   Christensen, Samuel; Huang, Yitong; Walch, Olivia J.; Forger, Daniel B. (December 2020, PLOS Computational Biology)

   Csikász-Nagy, Attila (Ed.)

   Which suggestions for behavioral modifications, based on mathematical models, are most likely to be followed in the real world? We address this question in the context of human circadian rhythms. Jet lag is a consequence of the misalignment of the body’s internal circadian (~24-hour) clock during an adjustment to a new schedule. Light is the clock’s primary synchronizer. Previous research has used mathematical models to compute light schedules that shift the circadian clock to a new time zone as quickly as possible. How users adjust their behavior when provided with these optimal schedules remains an open question. Here, we report data collected by wearables from more than 100 travelers as they cross time zones using a smartphone app, Entrain . We find that people rarely follow the optimal schedules generated through mathematical modeling entirely, but travelers who better followed the optimal schedules reported more positive moods after their trips. Using the data collected, we improve the optimal schedule predictions to accommodate real-world constraints. We also develop a scheduling algorithm that allows for the computation of approximately optimal schedules "on-the-fly" in response to disruptions. User burnout may not be critically important as long as the first parts of a schedule are followed. These results represent a crucial improvement in making the theoretical results of past work viable for practical use and show how theoretical predictions based on known human physiology can be efficiently used in real-world settings. 

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3. Potential bidirectional communication between the liver and the central circadian clock in MASLD

   https://doi.org/10.1038/s44324-025-00058-1  

   Gachon, Frédéric; Bugianesi, Elisabetta; Castelnuovo, Gabriele; Oster, Henrik; Pendergast, Julie S; Montagnese, Sara (April 2025, npj Metabolic Health and Disease)

   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. 

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4. Not all gut cellular circadian oscillators are food entrainable

   https://doi.org/10.1073/pnas.2601012123  

   Magaña, Isabel; Taufique, S_K Tahajjul; Shan, Yongli; Shen, Melody; Ehichioya, David E; Takahashi, Joseph S; Yamazaki, Shin; Obata, Yuuki (June 2026, Proceedings of the National Academy of Sciences)

   Circadian rhythms are ubiquitous, and most of the organs in the body contain circadian oscillators. The intestine comprises diverse cell types with distinct developmental origins and physiological functions. However, which intestinal cells contain cell-autonomous circadian oscillators and how circadian oscillators in distinct intestinal cell types synchronize with one another and with environmental daily cycles remain poorly understood. To address these questions, we generated a Cre-dependent PER2::LUCIFERASE reporter knock-in mouse that enables ex vivo measurement of circadian oscillations in defined cell populations. Ex vivo gut explants from mice expressing the reporter in one of five major cell types of the muscularis externa—enteric neurons (ENs), enteric glial cells (EGCs), interstitial cells of Cajal (ICCs), smooth muscle cells (SMCs), and muscularis macrophages (MMs)—exhibited robust, self-sustained circadian bioluminescence rhythms, demonstrating that each of these cell types harbors a cell-autonomous circadian oscillator. Importantly, circadian oscillators in ENs, EGCs, SMCs, and MMs entrained to feeding-fasting cycles, whereas circadian oscillators in ICCs remained resistant to food entrainment. These findings reveal that distinct intestinal cell types possess unique entrainment properties, and feeding during inactive time induces heterogeneous phase shifts across gut circadian oscillators, leading to temporal circadian misalignment within the intestine. As circadian disruptions, such as those associated with shift work, contribute to intestinal disorders, including inflammatory bowel disease and disorders of the gut–brain interaction, studying how intercellular circadian desynchrony influences intestinal homeostasis should provide chronobiology-based therapeutic strategies to combat these diseases. 

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5. Estimating Representative Group Intrinsic Circadian Period from Illuminance-Response Curve Data

   https://doi.org/10.1177/0748730419886992  

   Stack, Nora; Zeitzer, Jamie M.; Czeisler, Charles; Diniz Behn, Cecilia (April 2020, Journal of Biological Rhythms)

   The human circadian pacemaker entrains to the 24-h day, but interindividual differences in properties of the pacemaker, such as intrinsic period, affect chronotype and mediate responses to challenges to the circadian system, such as shift work and jet lag, and the efficacy of therapeutic interventions such as light therapy. Robust characterization of circadian properties requires desynchronization of the circadian system from the rest-activity cycle, and these forced desynchrony protocols are very time and resource intensive. However, circadian protocols designed to derive the relationship between light intensity and phase shift, which is inherently affected by intrinsic period, may be applied more broadly. To exploit this relationship, we applied a mathematical model of the human circadian pacemaker with a Markov-Chain Monte Carlo parameter estimation algorithm to estimate the representative group intrinsic period for a group of participants using their collective illuminance-response curve data. We first validated this methodology using simulated illuminance-response curve data in which the intrinsic period was known. Over a physiological range of intrinsic periods, this method accurately estimated the representative intrinsic period of the group. We also applied the method to previously published experimental data describing the illuminance-response curve for a group of healthy adult participants. We estimated the study participants’ representative group intrinsic period to be 24.26 and 24.27 h using uniform and normal priors, respectively, consistent with estimates of the average intrinsic period of healthy adults determined using forced desynchrony protocols. Our results establish an approach to estimate a population’s representative intrinsic period from illuminance-response curve data, thereby facilitating the characterization of intrinsic period across a broader range of participant populations than could be studied using forced desynchrony protocols. Future applications of this approach may improve the understanding of demographic differences in the intrinsic circadian period. 

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