Journal Of Biological Rhythms[JOURNAL]
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200 papers
Fetoplacental Circadian Rhythms Develop and Then Synchronize to the Mother In Utero.
Nikhil KL, Bates K, Sapiro E … +10 more , Amme JL, McCarthy R, Speck SL, Vasireddy V, Roberts E, Martin-Fairey CA, Domínguez-Romero ME, Cárdenas-García SP, England SK, Herzog ED
J Biol Rhythms · 2026 Apr · PMID 41960837 · Full text
Circadian rhythms in gene expression and hormones are ubiquitous across species and differentiated cell types, yet their developmental origins remain poorly understood. This study aimed to determine if daily rhythms can...
Circadian rhythms in gene expression and hormones are ubiquitous across species and differentiated cell types, yet their developmental origins remain poorly understood. This study aimed to determine if daily rhythms can be detected in utero and if they synchronize to the mother. We developed methods to longitudinally monitor PERIOD2 (PER2), a core circadian clock protein, from embryonic day (E)8.5 to E17.5 by restricting PER2::LUCIFERASE expression to the mouse fetoplacental unit (fetus and fetal-derived tissues). In utero fetoplacental bioluminescence imaging showed that PER2 levels increased during pregnancy, with variable daily peak times that stabilized to early night by E15.5. Interestingly, pregnancies that did not exhibit daily in utero PER2 variation were more likely to fail. Because maternal glucocorticoids have been implicated in fetal development and synchronizing other circadian tissues, we tested whether glucocorticoid injections could shift fetoplacental PER2 rhythms in utero. Daily subcutaneous corticosterone injections over 5 days of late pregnancy phase-dependently shifted the fetoplacental PER2 rhythms in utero. Blocking glucocorticoid signaling in vitro reduced synchrony between maternal and fetal placenta. We conclude that in utero daily rhythms gradually develop and synchronize with the mother prior to birth, potentially through glucocorticoid signaling.
Evolutionary Consequences of Selection on Circadian Accuracy.
Dani C
J Biol Rhythms · 2026 Apr · PMID 41960829 · Publisher ↗
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Seasonal Variation in Sleep, Respiratory, and Cardiovascular Parameters Assessed by a Wearable Device.
Vazquez IM, Palomino M, DelRosso LM
J Biol Rhythms · 2026 Apr · PMID 41960770 · Publisher ↗
Seasonal variation in sleep patterns is well recognized in PSG studies and actigraphy, yet few studies have comprehensively examined its impact on both sleep architecture and respiratory physiology using wearable technol...
Seasonal variation in sleep patterns is well recognized in PSG studies and actigraphy, yet few studies have comprehensively examined its impact on both sleep architecture and respiratory physiology using wearable technology. Circadian and environmental cues such as light exposure, temperature, and humidity may modulate sleep quality, apnea severity, and oxygenation, but large-scale, real-world data remain limited. We conducted a retrospective analysis of 2,386 home sleep studies, one study per individual, recorded between 2022 and 2025 using the SleepImage wearable system in Fresno, California. Each study was categorized by season of recording (winter, spring, summer, fall) based on start date. Key outcomes included total sleep duration, sleep latency, wake after sleep onset (WASO), mean and minimum SpO₂, apnea-hypopnea indices (sAHI3%, sAHI4%), respiratory disturbance indices (sRDI3%, sRDI4%), oxygen desaturation indices (ODI3%, ODI4%), and heart rate metrics. Analyses were adjusted for age using analysis of covariance (ANCOVA) and multiple linear regression to evaluate both main and interaction effects (). Significant seasonal differences were observed in multiple parameters after adjusting for age. Sleep latency was longest in summer (836.97 ± 1007.76 sec) and shortest in fall (582.51 ± 661.49 sec, < 0.001). Apnea hypopnea indices were highest in winter and lowest in fall ( = 0.027), while mean SpO₂ and maximum SpO₂ were modestly reduced in colder months ( < 0.001). Mean heart rate was higher in winter (68.3 ± 10.9 bpm) compared with summer (65.7 ± 9.3 bpm, < 0.001). Interaction models revealed that age modified seasonal effects on sleep efficiency and latency, with older adults showing greater winter-related sleep latency increases but smaller seasonal fluctuations in apnea indices. Sleep and respiratory parameters exhibit distinct seasonal modulation, with winter months associated with higher apnea burden and reduced oxygenation, and summer associated with prolonged sleep latency and greater fragmentation.
Daily Rhythms in Clock Gene mRNA Expression in Serotonergic Brain Regions of Adult Male Rats.
Strnad HK, Spencer RL
J Biol Rhythms · 2026 Apr · PMID 41958333 · Full text
Dysregulation of the serotonergic system is consistently noted in cases of psychiatric pathology. Circadian rhythm dysregulation is also a common comorbidity in psychiatric populations, and the circadian and serotonergic...
Dysregulation of the serotonergic system is consistently noted in cases of psychiatric pathology. Circadian rhythm dysregulation is also a common comorbidity in psychiatric populations, and the circadian and serotonergic systems have a long history of coregulation. Despite this, it is not yet known whether serotonergic neurons house circadian molecular clocks, the transcription and translation feedback loops that drive circadian rhythms at the cellular level. To investigate this, brain tissue was extracted from adult male rats every 4 h throughout the light-dark cycle. Radiolabeled in situ hybridization was used to quantify clock gene expression in the dorsal and median raphe, the two nuclei responsible for providing the majority of serotonin to the brain. We discovered oscillatory rhythms in the expression of clock genes , and with a period of approximately 24 h, and confirmed via fluorescent in situ hybridization that serotonergic (positive for , the rate-limiting enzyme in serotonin synthesis) neurons do express clock genes. The roughly antiphasic relationship between and the genes supports the existence of a circadian molecular clock in these cells. We next measured clock gene expression in neighboring brainstem regions that were not serotonergic, and found that although they all had similar daily clock gene expression profiles, the dorsal and median raphe had higher amplitude expression, and trending higher amplitude expression. This study adds to the growing list of extra-SCN (suprachiasmatic nucleus) molecular clocks reported in the brain. The prevalence of this circadian machinery, especially in regions of the brain so relevant to psychiatric health, underscores the importance of circadian rhythms to well-being. A greater understanding of the unique nature of circadian rhythms in discrete brain regions is a fruitful frontier for improving psychiatric treatment outcomes and overall health.
Circadian Rhythms Time Seizure Severity in .
Huertas-Radi M, Bradlaugh AA, Baines RA
J Biol Rhythms · 2026 Apr · PMID 41958013 · Publisher ↗
It is established that epilepsy patients can exhibit 24-h rhythms in seizure severity and occurrence. While the pathways underlying seizure rhythmicity remain poorly understood, it seems likely that a contribution from t...
It is established that epilepsy patients can exhibit 24-h rhythms in seizure severity and occurrence. While the pathways underlying seizure rhythmicity remain poorly understood, it seems likely that a contribution from the biological clock is involved. A better understanding of any such contribution may translate to better treatments. Here, the influence of the 24-h circadian rhythm on seizure activity in is investigated. Seizure-susceptible bang-sensitive mutants ( and ) were subjected to mechanically induced seizure at 6 different zeitgeber points. A clear sex-dependent phenotype was observed, with seizure severity showing a greater time-of-day effect in females than males. The temporal pattern of seizure recovery time was bimodal, exhibiting both a morning and an evening peak. Rearing flies in constant light (LL), which renders the molecular clock dysfunctional, abolished the seizure rhythm. Conversely, female seizure mutants reared in constant darkness (DD), allowing free running of the circadian clock, continued to exhibit a bimodal rhythm of seizure severity. Moreover, seizure mutant females lacking a functional clock () did not show rhythmicity of seizure severity. These findings support a role for the biological clock in seizure activity, at least in female . Finally, seizure mutant females showed normal PERIOD clock protein intensity oscillations in clock neurons, supporting the hypothesis that seizure rhythmicity requires a functional circadian clock. Thus, this study validates as a potential model for the identifying the mechanisms modulating seizure rhythmicity, with the potential to aid future treatment of epilepsy.
Actigraphy-Based Movement Profiles and Their Association With Circadian Rhythms Integrity in Real-World Settings.
Marchesano M, Silva A, Tassino B
J Biol Rhythms · 2026 Apr · PMID 41944595 · Publisher ↗
Both active movement profiles and robust circadian rhythms are linked to improved health outcomes, yet the underlying mechanisms remain partially understood. We investigated this relationship in young adults ( = 169, age...
Both active movement profiles and robust circadian rhythms are linked to improved health outcomes, yet the underlying mechanisms remain partially understood. We investigated this relationship in young adults ( = 169, aged 18-30 years) under real-world conditions using actigraphy data. We performed k-means clustering on 12 accelerometer-based features capturing magnitude, duration, frequency, and intensity distribution to derive movement behavior profiles. As a proxy of circadian rhythms integrity, we computed the Circadian Function Index (CFI), which combines intradaily variability, interdaily stability, and relative amplitude. We also assessed circadian phase and sleep quality parameters. In addition, we quantified light exposure and physical activity over 3-h daily intervals. The unsupervised algorithm identified 2 non-overlapping profiles among participants, the More Active (MA) and the Less Active (LA) profiles. MA exhibited a higher CFI (0.81 ± 0.06 vs 0.69 ± 0.06, < 0.001), which was also positively associated with early-evening physical activity, but not with light exposure. MA also showed an earlier activity-based phase indicator, the midpoint of the 5 least-active hours (L5c, 04:30 ± 01:03 vs 04:59 ± 01:15, adj. = 0.04), which was inversely associated with early-morning physical activity and late-morning light exposure. We found no differences in sleep quality between MA and LA. Our results underscore the association between movement behavior and overall circadian rhythms integrity. Importantly, these findings reinforce actigraphy as a multidimensional tool for both health research and clinical applications.
Overnight Motor Memory Consolidation in Adolescents: Effects of Change in Dim Light Melatonin Onset After Sleep Restriction.
Stager L, Gredvig-Ardito C, Crowley S … +3 more , Seifer R, Carskadon M, Saletin J
J Biol Rhythms · 2026 Apr · PMID 41943473 · Full text
Adolescents experience chronic sleep restriction and developmental changes in circadian biology. Sleep aids adolescent learning and memory; the moderating effect of circadian rhythms is largely unknown. Here we examine a...
Adolescents experience chronic sleep restriction and developmental changes in circadian biology. Sleep aids adolescent learning and memory; the moderating effect of circadian rhythms is largely unknown. Here we examine adolescent sleep restriction, circadian biology, and memory consolidation. Adolescents were recruited for a larger experimental study. This study includes a subsample of individuals from the larger study who completed the motor sequence task (MST; added toward the end of data collection). Participants ( = 12.7, = 1.8; 62.5% male) completed a self-selected 9 h in bed sleep stabilization schedule for 19 nights followed by 7 nights of sleep restriction (6 h in bed; bedtime delayed and risetime advanced equally). In-lab dim light melatonin onset (DLMO) was assessed on the final nights of stabilization and restriction. The MST indexed overnight memory consolidation across the final night of sleep restriction. MST outcomes included the average number of correct sequences per trial, # of errors, and precision. We examined overnight improvement (morning-evening) in MST performance and associations between improvement, phase preference, DLMO, DLMO, and DLMO (DLMO - DLMO), controlling for age where statistically justified. The average number of correct sequences per MST trial improved, (15) = -3.44, < 0.01, = 0.86, for the morning (12.94 ± 6.89) test session compared to evening (10.81 ± 5.69). There were no changes in errors or precision (s < 0.14, s > 0.34). Greater delays in DLMO phase ( ± : 10.34 ± 41.69 min) were associated with greater overnight improvement in the average number of correct sequences per trial, Adj. = 0.54, (2, 13) = 9.79, < 0.01, and errors, Adj. = 0.21, (1, 15) = 4.94, < 0.05. Overnight improvement was not related to phase preference (Adj. s < 0.17; s > 0.05). These data highlight context dependent benefits of sleep for adolescent memory consolidation and indicate a potential link between circadian biology and the cognitive benefits of adolescent sleep. Understanding the influence of circadian rhythms in sleep-dependent memory may inform discussions of adolescent sleep loss and learning.
Initial Condition Decision to Ensure Reliable Circadian Phase Estimation With Shorter-Term Wearable Data.
Lim D, Kim J, Kim JH … +1 more , Kim JK
J Biol Rhythms · 2026 Apr · PMID 41928495 · Publisher ↗
Various studies in the medical field highlight the importance of circadian medicine, which optimizes treatment timing based on patients' circadian phases. While the circadian phase has been measured using dim light melat...
Various studies in the medical field highlight the importance of circadian medicine, which optimizes treatment timing based on patients' circadian phases. While the circadian phase has been measured using dim light melatonin onset (DLMO), the gold standard marker, its high cost and time-intensive nature have led to the development of alternative estimation methods. Among these, the most promising method is using ordinary differential equation (ODE) models, which simulate the circadian rhythm by using a light exposure profile estimated from sleep data. These ODE models require an initial condition (IC) representing the initial state of the circadian rhythm, which is unknown in real-world settings. However, it is unclear how the uncertainty of IC affects the accuracy of circadian phase estimation. In this study, by using sleep data collected from 28 shift workers using ActiWatch (mean duration = 56 days, range = 34-75 days), we found that ≥18 days of sleep data are required for the circadian phase to become independent of the subjective IC choice. The result showed that without an accurate IC, circadian phase estimation is dependent on subjective IC choice, meaning that circadian phase estimates in the first 17 days are not reliable. Indeed, these days were reduced to 11-14 days on average when previous studies' IC estimation methods were used. To further shorten this length, we developed new IC estimation methods-period-based and work history-based sleep methods-that incorporate daily variations in sleep history. Notably, the new methods reduced the number of days required for reliable circadian phase estimation to about 5 days. Hence, our approach allows a larger portion of circadian phase estimates from given sleep data to be used as reliable information. The superiority of our methods paves the way for improved circadian phase estimation, ultimately enhancing the practicality of chronotherapy applications.
: An Open-Source R Package for the Dim-Light Melatonin Onset (DLMO) Hockey-Stick Method.
Thalji SM, Spitschan M
J Biol Rhythms · 2026 Jun · PMID 41684108 · Full text
The dim-light melatonin onset (DLMO) is a commonly used circadian marker indicating the start time of evening melatonin synthesis in humans. Several quantitative techniques have been developed to determine DLMO from mela...
The dim-light melatonin onset (DLMO) is a commonly used circadian marker indicating the start time of evening melatonin synthesis in humans. Several quantitative techniques have been developed to determine DLMO from melatonin time series, including fixed- or variable-threshold techniques and the hockey-stick method developed by Danilenko et al (2014). Here, we introduce , an open-source (MIT License) implementation of the hockey-stick method written in R. Our clean-room implementation follows the original algorithm description, supported by iterative validation against the existing binary executable. We benchmarked on 112 melatonin time series data sets from two independent studies and found high agreement with the reference implementation: mean discrepancies were min for the Heinrichs and Spitschan (2025) data set and min for the Blume et al. (2024) data set, with circular correlation coefficients of 0.964 and 0.986, respectively. Paired -tests () indicated no systematic difference or bias between methods. Beyond reproducing the hockey-stick algorithm, adds capabilities absent from the original executable, including interactive visual diagnostics and bootstrapped confidence intervals, offering qualitative and quantitative views of estimation uncertainty. It supports programmatic, reproducible analysis of melatonin profiles, including batch processing and parameter manipulation. Leveraging this flexibility, we evaluated the sensitivity of the hockey-stick algorithm to controlled changes in sampling schedules, threshold levels, data completeness, and noise. Moderate changes, such as small timing jitter, limited data loss, or modest threshold shifts, kept estimates stable within ±10 min, whereas pronounced alterations to sampling schedules, large multi-point deletions, or substantial threshold changes delayed estimates by over 40 min or prevented estimation. This analysis reveals fundamental limitations in the algorithm's internal mechanics, particularly in how it identifies the onset window and models the melatonin rise, and underscores the need for new uncertainty-aware approaches to DLMO estimation.
Circadian Timing Moderates Diurnal Positive Affect Rhythms in Adolescents.
Mirchandaney R, Wescott DL, Kuzemchak MC … +7 more , Quick AD, Guo K, Clark DB, Buysse DJ, Siegle GJ, Wallace ML, Hasler BP
J Biol Rhythms · 2026 Jun · PMID 41621053 · Full text
In adult samples, tightly-controlled laboratory studies indicate the presence of circadian rhythms in positive (and negative) affect. Naturalistic studies also suggest the presence of diurnal positive affect rhythms in a...
In adult samples, tightly-controlled laboratory studies indicate the presence of circadian rhythms in positive (and negative) affect. Naturalistic studies also suggest the presence of diurnal positive affect rhythms in adults, the characteristics (acrophase, mesor, and amplitude) of which vary by self-report circadian preference-greater evening preference is associated with later acrophase, lower mesor, and lower amplitude in positive affect. We examined the extent to which diurnal affect rhythms are associated with 4 different measures of circadian timing, including dim light melatonin onset, in a sample of high-school adolescents who reported at least one drink of alcohol in their lifetime ( = 126, 17.3 ± 0.87 years, 55.6% female). Cosinor models found support for robust diurnal rhythms in positive, but not negative, affect. The overall modeled positive affect rhythm had an acrophase at 3:39 PM, a mesor of 9.77, and an amplitude of 1.61. Later circadian timing was associated with later acrophase in positive affect rhythms across the following measures: circadian preference (3:00 PM vs 4:20 PM, < .001), chronotype (3:20 PM vs 4:11 PM, = .014), and actigraphy-based midsleep (3:08 PM vs 4:16 PM, = .014). We did not find significant associations between circadian phase (dim light melatonin onset) and positive affect rhythms. We also explored weekday-weekend differences in positive affect rhythms, finding significantly higher mesor (9.71 vs 9.99, = .004) and lower amplitude (1.69 vs 1.26, = .008) on the weekends than weekdays. In sum, compared to their peers, adolescents with later sleep and circadian timing experience a delayed peak in positive affect during the day, which may have consequences for behavioral activation and depressed mood. These findings underscore the importance of considering the role of sleep and circadian factors in affective processes during adolescence.
Menstrual Cycle Temperature Dynamics and Their Association With Conception: A Within- and Between-Person Analysis.
Kiss O, Gombert-Labedens M, Taitz A … +1 more , Baker FC
J Biol Rhythms · 2026 Jun · PMID 41588649 · Publisher ↗
Temperature regulation across the menstrual cycle follows predictable rhythmic changes driven by reproductive hormones, particularly the thermogenic effect of progesterone in the luteal phase. While basal body temperatur...
Temperature regulation across the menstrual cycle follows predictable rhythmic changes driven by reproductive hormones, particularly the thermogenic effect of progesterone in the luteal phase. While basal body temperature has long been used to identify ovulatory cycles, it is less clear how detailed features of the temperature rhythm, including its strength (amplitude) and timing (phase), relate to the likelihood of conception, especially when accounting for individual variability in cycle length and age. Here, we aimed to examine associations between menstrual temperature rhythm characteristics and conception likelihood using both between-person and within-person analyses. We analyzed daily temperature data from 423 women (19-40 years) contributing 4682 cycles, who were participants in a multi-country study about fertility conducted between 1992 and 1996 ("Fertili" dataset). Cycle-level temperature fluctuations were modeled using linear mixed-effects models (GLMMs) with cosine and sine terms scaled to each cycle's length, from which amplitude and phase parameters were derived. At the level of consecutive cycle-series (sessions), GLMMs assessed whether rhythm features, mean temperature, cycle length, cycle regularity, and age predicted conception. Within-person analyses compared pre-conceptive and non-conceptive cycles from the same individual, restricted to cycles with sexual intercourse during the fertile window. Temperature showed a robust oscillatory pattern across the menstrual cycle. At the session level, higher mean temperature was associated with greater conception likelihood in the pre-conceptive cycles, and phase in temperature rhythms tended to be beneficial, particularly in longer cycles. A 3-way interaction revealed that conception was most likely in cycles following shorter cycles (≤35 days) when temperature rhythms were both high in amplitude and well-timed in phase, whereas in longer cycles, rhythm timing appeared to play a larger role than amplitude alone. Within-person comparisons showed that larger temperature phase occurred more often in pre-conceptive cycles than in cycles not followed by conception. Both the magnitude and timing of menstrual temperature rhythms carry information about potential for conception beyond the detection of a post-ovulatory rise. Conception appears most likely when strong rhythmicity aligns optimally with the fertile window in typical length cycles.
The Effect of Night Shift Work on the Gut Microbiome Diversity: The EXPONIT Study.
Galan R, Castaño-Vinyals G, Rubio-Garcia E … +11 more , Lopez-Aladid R, Espinosa A, Papantoniou K, Bustamante M, Bhatti P, Lassale C, Márquez C, Alfaro A, Casals-Pascual C, Kogevinas M, Harding BN
J Biol Rhythms · 2026 Jun · PMID 41582394 · Publisher ↗
Night shift work may alter the gut microbiome through mechanisms involving circadian misalignment, sleep disturbance, and changes in dietary behavior. However, existing studies on this topic have been limited in sample s...
Night shift work may alter the gut microbiome through mechanisms involving circadian misalignment, sleep disturbance, and changes in dietary behavior. However, existing studies on this topic have been limited in sample size and scope. We analyzed stool samples from 240 participants (mean age 42 years, 80% women), of whom 53% were night shift workers. Gut microbiota composition was assessed using 16S rRNA gene sequencing to derive measures of relative abundance, alpha diversity, and beta diversity. Associations between night shift work and microbial composition and alpha diversity were examined using generalized linear models with a Gamma distribution and log link for alpha diversity and Aitchison distance for beta diversity. The effect of night shift work on microbiome genera abundance was evaluated using MaAsLin2 analysis. Models were adjusted for age, sex, and educational level. We also explored potential interactions by sleep quality, diet, and chronotype. There were no overall significant differences in alpha or beta diversity between day and night shift workers, but participants with less than 15 years of night work showed slightly higher Abundance-based Coverage Estimator than non-night workers. Interaction with sleep quality was observed (-value: 0.01). Among participants with poor sleep quality, night shift work was significantly associated with lower alpha diversity (exp(β): 0.93, 95% CI: 0.87-0.99, -value: 0.02). Day shift workers showed high relative abundance of , while night shift workers had increased at descriptive level, none of which remain statistically significant after false discovery rate. Our findings indicate that night shift work may influence gut microbiome diversity, especially in individuals with poor sleep quality. Future research should explore the long-term health consequences of these microbial changes.
Looking Back at JBR 2020-2025.
Harrington M
J Biol Rhythms · 2026 Feb · PMID 41578625 · Publisher ↗
Abstract loading — click title to view on PubMed.
Malcolm von Schantz.
Skene DJ, Archer SN, Moreno CRC … +1 more , Ellis J
J Biol Rhythms · 2026 Jun · PMID 41577631 · Publisher ↗
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Stool Dynamics and the Developing Gut Microbiome During Infancy.
Al-Andoli M, Schoch S, Markovic A … +7 more , Mühlematter C, Beaugrand M, Jenni OG, Liamlahi R, Walser JC, Nielsen D, Kurth S
J Biol Rhythms · 2026 Jun · PMID 41558673 · Full text
The infant gut microbiome is a dynamic ecosystem, and it is key to early development, immune maturation, and overall health. Recent insights reveal that the gut microbiota undergoes changes across the 24-h day, raising t...
The infant gut microbiome is a dynamic ecosystem, and it is key to early development, immune maturation, and overall health. Recent insights reveal that the gut microbiota undergoes changes across the 24-h day, raising the possibility that it may act as a "zeitgeber," supporting the host's sleep-wake organization. Despite its importance, timing factors influencing microbiome composition are poorly understood, limiting its use as a health indicator. This study investigates the relationship between stool dynamics (defecation interval, time of sampling), sleep pressure (interval since last sleep), meal timing, and gut microbial composition. Stool samples from 198 healthy infants, aged 3 to 31 months, were analyzed to assess microbial diversity, richness evenness, and abundance. Our findings reveal that longer intervals between bowel movements are associated with increased microbial diversity, evenness, and richness. Stool timing is associated with shifts in microbial composition, especially in younger infants, indicating diurnal microbial fluctuations to become more stable as infants mature. Longer periods of wakefulness were associated with increased microbial diversity in early infancy, although this effect appeared to diminish with age. Feeding schedules had limited effects on the gut microbiome. Longer fasting before sampling showed no significant associations with most microbial parameters, except for a positive association with microbial richness. At the phylum level, results indicate that infant gut microbial composition is influenced by behavior and physiology. Longer intervals between bowel movements were associated with shifts in bacterial abundance, with decreasing and increasing. In addition, later stool sampling times revealed higher levels, and longer fasting was associated with reduced . Sleep pressure showed a trend effect with displaying a slight decrease in infants who had been awake longer. Our findings underscore the importance of time-based factors on infant gut microbiome composition.
When Clocks Go Rogue: Circadian Rhythms and the Rise of Cancer.
Robinson AS, Bennett S, Sato S
J Biol Rhythms · 2026 Apr · PMID 41520235 · Publisher ↗
This review summarizes recent insights into the roles of the circadian clock in regulating cancer hallmarks, with a focus on its impact on the tumor microenvironment, and highlights the translational promise of circadian...
This review summarizes recent insights into the roles of the circadian clock in regulating cancer hallmarks, with a focus on its impact on the tumor microenvironment, and highlights the translational promise of circadian-informed strategies for cancer therapy. The circadian clock is a 24-hour biological timekeeping system that aligns physiological processes with cyclic environmental cues, such as light-dark cycles. Disruptions of circadian rhythms caused by lifestyle factors, including shift work, irregular sleep patterns, and jet lag, can lead to physiological dysregulation and increased risk of various diseases including cancer, positioning the circadian clock as both a critical driver of tumorigenesis and a potential target for chronotherapies. This review provides a comprehensive overview of circadian regulation in tumorigenesis across diverse cancer types by framing its role according to established cancer hallmarks, with particular emphasis on how the circadian system shapes immune cell dynamics within the tumor microenvironment to modulate tumor progression and immune surveillance. We further discuss recent preclinical and clinical advances in chronotherapy, highlighting how aligning therapeutic interventions with biological rhythms can enhance treatment efficacy, including responses to immunotherapy. By integrating mechanistic insights with translational applications, this review bridges circadian biology and oncology, providing a framework for future chronobiology-based cancer therapies.
The Liver Clock Tunes Transcriptional Rhythms in Skeletal Muscle to Regulate Mitochondrial Function.
Sica V, Sato T, Tsialtas I … +7 more , Hernandez S, Chen S, Baldi P, Muñoz-Cánoves P, Sassone-Corsi P, Koronowski KB, Smith JG
J Biol Rhythms · 2026 Apr · PMID 41486525 · Full text
Circadian clocks present throughout the brain and body coordinate diverse physiological processes to support daily homeostasis, yet the specific interorgan signaling axes involved are not well defined. We previously demo...
Circadian clocks present throughout the brain and body coordinate diverse physiological processes to support daily homeostasis, yet the specific interorgan signaling axes involved are not well defined. We previously demonstrated that the skeletal muscle clock controls transcript oscillations of genes involved in fatty acid metabolism in the liver, yet the impact of the liver clock on the muscle remained unknown. Here, we use male hepatocyte-specific KO mice (Bmal1) to reveal that approximately one-third of transcript rhythms in skeletal muscle are influenced by the liver clock in vivo. Treatment of myotubes with serum harvested from Bmal1 mice inhibits expression of genes involved in metabolic pathways, including oxidative phosphorylation. Only small transcriptional changes were induced by liver clock-driven endocrine communication in vitro, leading us to surmise that the liver clock acts to fine-tune metabolic gene expression in muscle. Consistent with functional tuning, treatment of myotubes with serum collected from mice during the dark phase lowers mitochondrial ATP production compared with serum from wild-type mice. Overall, our results reveal communication between the liver clock and skeletal muscle, uncovering a bidirectional endocrine communication pathway that may contribute to the metabolic phenotypes of circadian disruption.
Rhythmicity of TOR (Target of Rapamycin) Activity Supports Circadian Function in .
Akhtari G, Falahat Chian M, Sooklal EM … +1 more , Lakin-Thomas P
J Biol Rhythms · 2026 Apr · PMID 41472420 · Full text
Circadian (24 h) rhythmicity is a nearly-ubiquitous property of eukaryotic cells, and the mechanisms that generate this rhythmicity have been studied in a number of organisms for many years. However, there are still gaps...
Circadian (24 h) rhythmicity is a nearly-ubiquitous property of eukaryotic cells, and the mechanisms that generate this rhythmicity have been studied in a number of organisms for many years. However, there are still gaps in our understanding of the generation and regulation of rhythms. Although transcription/translation feedback loops (TTFLs) are said to be essential to generating rhythmicity in eukaryotes, there are many examples of rhythmicity seen in organisms without functioning TTFLs. Our lab previously found that two genes that function in the TOR (Target of Rapamycin) pathway, and , are essential for non-TTFL rhythmicity in the fungus These two mutants were also shown to dampen the output rhythm of spore-formation (conidiation) and the rhythm of the TTFL component protein FRQ, and dampen the amplitude of the underlying oscillator in strains with functioning TTFLs. Therefore, we are interested in the role of TOR in generating and/or sustaining rhythmicity in both the presence and absence of a functioning TTFL. Here we report the development and validation of an improved assay for TOR activity in , and using this assay we demonstrate that TOR activity displays circadian rhythmicity in strains with functioning TTFLs. The period of TOR rhythmicity is affected by a long-period mutation in a TTFL component (), and the TOR rhythm is dampened in the and knockouts. The mean level of TOR activity (mesor) in the and knockout mutants is within the range of the TOR rhythm in wild type, indicating that it is rhythmicity of TOR, not a constant level of activity, that is required to sustain output rhythmicity. These results establish as a valuable model for investigating the role of TOR in circadian rhythmicity and implicate TOR activity as a rhythmic state variable of the circadian system.
Phylogeny of Core Molecular Components of Metazoan Circadian Clocks.
Waldridge OM, Eşkut KI, Smith JJ … +1 more , Cassone VM
J Biol Rhythms · 2026 Apr · PMID 41453835 · Publisher ↗
The temporal organization of biological activities by circadian clocks is pivotal for the survival of organisms. Significant progress has been made in understanding the molecular foundations of animal circadian clocks th...
The temporal organization of biological activities by circadian clocks is pivotal for the survival of organisms. Significant progress has been made in understanding the molecular foundations of animal circadian clocks through the characterization of key components, such as CLOCK, BMAL1/Cycle (CYC), Period (PER), Timeless, and Cryptochrome (CRY) in several model organisms. To determine the extent of conservation of these elements, we investigated the sequences of these genes and their paralogs across 46 animal species that encompass multiple phyla in the Metazoan kingdom to resolve the relative timing of duplication and loss events that have diversified core clock components. Using analyses of orthology and protein-protein binding predictions, we identified and characterized elements in diverse animal species. Based on these analyses, we propose a circadian molecular mechanism employed by the ancestor of all animals. We also identify derived losses and expansions of circadian elements in smaller animal clades and provide insight into the evolutionary pressures faced by their ancestors to change such an important piece of internal machinery. Our study is the first systematic analysis of the deep phylogeny of nearly all major clades of extant animals.
Decline in Circadian Robustness in Lung Cancer Patients During Immunotherapy is Associated With Increased Risk of Disease Progression and Death.
Strøm L, Amidi A, Wu LM … +5 more , Meldgaard P, Ancoli-Israel S, Lekander M, Mroczek D, Zachariae R
J Biol Rhythms · 2026 Apr · PMID 41439528 · Publisher ↗
Disruptions in sleep and circadian rhythms have been consistently linked to higher mortality rates in the general population. Among cancer patients, these disruptions are not only prevalent but may significantly influenc...
Disruptions in sleep and circadian rhythms have been consistently linked to higher mortality rates in the general population. Among cancer patients, these disruptions are not only prevalent but may significantly influence prognosis. Despite this, sleep and circadian trajectories remain unexplored in the context of cancer, particularly related to prognostic outcomes in modern therapies such as immune checkpoint inhibitors (ICIs), which are rapidly transforming oncological care. In this pioneering report, we examined how trajectories of sleep and circadian rhythms relate to prognostic outcomes in patients with non-small cell lung cancer (NSCLC), offering novel insights into their potential role as modifiable biomarkers of clinical outcomes. Forty-nine treatment-naïve NSCLC patients were enrolled in this prospective longitudinal study. Continuous 24-h recordings of circadian function (Circadian Function Index [CFI]) were collected over the first 5 months of treatment, alongside weekly assessments of insomnia severity (Insomnia Severity Index [ISI]) and estimations of total sleep time (TST) derived from sleep diaries every 3 weeks. Follow-up data, time to treatment discontinuation, disease progression, and cancer-related death were obtained from medical records. We estimated hazard ratios (HRs) for these outcomes based on ISI, TST, and CFI, analyzed as continuous variables and median-split. Cox regression analyses indicated that patients with trajectories portraying circadian robustness below the median had a higher risk of earlier progression (HR = 3.75, 95% confidence interval [CI] = [1.475-9.536], = 0.005) and death (HR = 3.07, 95% CI = [1.128-8.360], = 0.028). No significant associations were found between insomnia severity, TST, and the prognostic outcomes. Patients with more pronounced declines in circadian robustness demonstrated significantly elevated risks of disease progression and mortality. As the circadian rhythm is modifiable, these findings, if replicated, underscore the need for interventional studies aimed at stabilizing circadian rhythms to further explore potential improvements in patient outcomes and efficacy of cancer therapies.
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