scholarly journals Circadian benefits of exercise training reflect metabolic and structural flexibility

2020 ◽  
Author(s):  
Drew Duglan ◽  
Nuria Casanova-Vallve ◽  
Megan E. Vaughan ◽  
Michal K. Handzlik ◽  
Weiwei Fan ◽  
...  

AbstractIdentifying molecular adaptations underlying improved fitness in response to training is of critical interest in exercise physiology. Circadian rhythms broadly modulate metabolism, including muscle substrate utilization and exercise capacity. Here we show that time of day influences the increase in exercise capacity afforded by training: when maximum running speed is measured at the beginning of the nighttime active period in mice, there is no measurable benefit from training, while maximum increase in performance occurs at the end of the night. Incidentally, we describe an improved method to motivate running in rodent exercise studies that obviates the use of electrical stimulation. Furthermore, we describe daily rhythms in carbohydrate and lipid metabolism and transport associated with the time-dependent response to training. Thus, we show that circadian rhythms modulate muscle-intrinsic responses to training and provide resources for the optimal design of exercise studies in rodents.

2014 ◽  
Vol 112 (3) ◽  
pp. 905-910 ◽  
Author(s):  
Amaury de Montaigu ◽  
Antonis Giakountis ◽  
Matthew Rubin ◽  
Réka Tóth ◽  
Frédéric Cremer ◽  
...  

Daily rhythms of gene expression provide a benefit to most organisms by ensuring that biological processes are activated at the optimal time of day. Although temporal patterns of expression control plant traits of agricultural importance, how natural genetic variation modifies these patterns during the day and how precisely these patterns influence phenotypes is poorly understood. The circadian clock regulates the timing of gene expression, and natural variation in circadian rhythms has been described, but circadian rhythms are measured in artificial continuous conditions that do not reflect the complexity of biologically relevant day/night cycles. By studying transcriptional rhythms of the evening-expressed gene GIGANTEA (GI) at high temporal resolution and during day/night cycles, we show that natural variation in the timing of GI expression occurs mostly under long days in 77 Arabidopsis accessions. This variation is explained by natural alleles that alter light sensitivity of GI, specifically in the evening, and that act at least partly independent of circadian rhythms. Natural alleles induce precise changes in the temporal waveform of GI expression, and these changes have detectable effects on PHYTOCHROME INTERACTING FACTOR 4 expression and growth. Our findings provide a paradigm for how natural alleles act within day/night cycles to precisely modify temporal gene expression waveforms and cause phenotypic diversity. Such alleles could confer an advantage by adjusting the activity of temporally regulated processes without severely disrupting the circadian system.


2020 ◽  
Author(s):  
Casey O. Diekman ◽  
Ning Wei

AbstractSudden cardiac arrest is a malfunction of the heart’s electrical system, typically caused by ventricular arrhythmias, that can lead to sudden cardiac death (SCD) within minutes. Epidemiological studies have shown that SCD and ventricular arrhythmias are more likely to occur in the morning than in the evening, and laboratory studies indicate that these daily rhythms in adverse cardiovascular events are at least partially under the control of the endogenous circadian timekeeping system. However, the biophysical mechanisms linking molecular circadian clocks to cardiac arrhythmogenesis are not fully understood. Recent experiments have shown that L-type calcium channels exhibit circadian rhythms in both expression and function in guinea pig ventricular cardiomyocytes. We developed an electrophysiological model of these cells to simulate the effect of circadian variation in L-type calcium conductance. We found that there is a circadian pattern in the occurrence of early afterdepolarizations (EADs), which are abnormal depolarizations during the repolarization phase of a cardiac action potential that can trigger fatal ventricular arrhythmias. Specifically, the model produces EADs in the morning but not at other times of day. We show that the model exhibits a codimension-2 Takens-Bogdanov bifurcation that serves as an organizing center for different types of EAD dynamics. We also simulated a 2-D spatial version of this model across a circadian cycle. We found that there is a circadian pattern in the breakup of spiral waves, which represents ventricular fibrillation in cardiac tissue. Specifically, the model produces spiral wave breakup in the morning but not in the evening. Our study is the first to propose a link between circadian rhythms and EAD formation and suggests that the efficacy of drugs targeting EAD-mediated arrhythmias may depend on the time of day that they are administered.Significance StatementWhy are life-threatening cardiac arrhythmias more likely to occur in the morning than in the evening? The electrical properties of the heart exhibit daily rhythms due to molecular circadian clocks within cardiomyocytes. Our computational model of ventricular myocytes shows that clock-controlled expression of a voltage-gated calcium ion channel leads to early afterdepolarizations (EADs) at certain times of the day. EADs, in which the membrane potential of a cardiomyocyte depolarizes a second time before fully repolarizing, can trigger arrhythmias. To our knowledge, this is the first study linking the circadian clock to EAD formation. Our results suggest that the efficacy of anti-arrhythmic medications targeting this calcium ion channel may depend on the time of day the drug is taken.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A118-A118
Author(s):  
Gabriela Caetano ◽  
Laura Kervezee ◽  
Fernando Gonzales-Aste ◽  
Philippe Boudreau ◽  
Diane Boivin

Abstract Introduction National reports of work-related injuries found the excess risk of work injury attributed to shift work to be significantly higher among women. The Working Time Society (WTS) concluded that male sex is one of the few factors that is “consistently associated with perceived or actual shift work tolerance”. However, it is unclear if physiological parameters are involved. Laboratory-controlled studies report sex differences in circadian rhythms (body temperature, melatonin). In sleep deprivation protocols, alertness and cognitive performances were affected by sex, menstrual cycle phase and hormonal contraceptives [HC] use. Nevertheless, field studies that compare male and female shift workers are scarce. Methods An observational study including 76 police officers working on patrol: 56 males and 20 females (11 using [HC], 6 not using [non-HC] and 3 with unknown use of hormonal contraception) aged 32.0 ± 5.3 years. Participants were followed throughout a month-long work cycle (1,457 morning, evening, night, or other shifts, plus rest days). They filled out time-stamped questionnaires (Samn-Perelli, KSS, Visual Analogue Scales, ~5/day; sleep and work-related information, ~1–2/day), completed 5-min Psychomotor Vigilance Tasks (PVT, ~2/day), and wore an actigraph to collect activity data. Linear mixed-effects models were used to analyze the effects of group, time awake and time-of-day on fatigue, sleepiness, alertness, mood and PVT measures. Results Self-reported measures and psychomotor performance significantly varied with time awake and time-of-day. Fatigue and sleepiness levels were significantly higher among female compared to male police officers, both with time awake and across the 24-h day. These variations were similar between non-HC females and the other groups. Compared to males, HC females were more fatigued and less alert, both with time awake and across the 24-h day, and sleepier with time awake. Having children at home did not explain these differences. Conclusion The results of this study expand our knowledge on the sex differences in the sleep and circadian physiology and demonstrate a critical effect of HC on women fatigue, sleepiness and alertness when working shifts. Sex and hormonal parameters must be considered in occupational medicine as well as in future laboratory and field studies on shift workers and circadian rhythms. Support (if any) IRSST, FRQS.


Author(s):  
Alíz T Y Owolabi ◽  
Sarah E Reece ◽  
Petra Schneider

Abstract Background and objectives Circadian rhythms contribute to treatment efficacy in several non-communicable diseases. However, chronotherapy (administering drugs at a particular time-of-day) against infectious diseases has been overlooked. Yet, the daily rhythms of both hosts and disease-causing agents can impact the efficacy of drug treatment. We use the rodent malaria parasite Plasmodium chabaudi, to test if the daily rhythms of hosts, parasites, and their interactions, affect sensitivity to the key antimalarial, artemisinin. Methodology Asexual malaria parasites develop rhythmically in the host’s blood, in a manner timed to coordinate with host daily rhythms. Our experiments coupled or decoupled the timing of parasite and host rhythms, and we administered artemisinin at different times of day to coincide with when parasites were either at an early (ring) or later (trophozoite) developmental stage. We quantified the impacts of parasite developmental stage, and alignment of parasite and host rhythms, on drug sensitivity. Results We find that rings were less sensitive to artemisinin than trophozoites, and this difference was exacerbated when parasite and host rhythms were misaligned, with little direct contribution of host time-of-day on its own. Furthermore, the blood concentration of haem at the point of treatment correlated positively with artemisinin efficacy but only when parasite and host rhythms were aligned. Conclusions and implications Parasite rhythms influence drug sensitivity in vivo. The hitherto unknown modulation by alignment between parasite and host daily rhythms suggests that disrupting the timing of parasite development could be a novel chronotherapeutic approach. Lay Summary We reveal that chronotherapy (providing medicines at a particular time-of-day) could improve treatment for malaria infections. Specifically, parasites’ developmental stage at the time of treatment and the coordination of timing between parasite and host both affect how well antimalarial drug treatment works.


2019 ◽  
Author(s):  
Kenya Tanaka ◽  
Ginga Shimakawa ◽  
Shuji Nakanishi

AbstractAs an adaptation to periodic fluctuations of environmental light, photosynthetic organisms have evolved a circadian clock. Control by the circadian clock of many cellular physiological functions, including antioxidant enzymes, metabolism and the cell cycle, has attracted attention in the context of oxidative stress tolerance. However, since each physiological function works in an integrated manner to deal with oxidative stress, whether or not cell responses to oxidative stress are under circadian control remains an open question. In fact, circadian rhythms of oxidative stress tolerance have not yet been experimentally demonstrated. In the present work, we applied an assay using methyl viologen (MV), which generates reactive oxygen species (ROS) under light irradiation, and experimentally verified the circadian rhythms of oxidative stress tolerance in photosynthetic cells of the cyanobacterium Synechococcus elongatus PCC7942, a standard model species for investigation of the circadian clock. Here, we report that ROS generated by MV treatment causes damage to stroma components and not to the photosynthetic electron transportation chain, leading to reduced cell viability. The degree of decrease in cell viability was dependent on the subjective time at which oxidative stress was applied. Thus, oxidative stress tolerance was shown to exhibit circadian rhythms. In addition, the rhythmic pattern of oxidative stress tolerance disappeared in mutant cells lacking the essential clock genes. Notably, ROS levels changed periodically, independent of the MV treatment. Thus, we demonstrate for the first time that in cyanobacterial cells, oxidative stress tolerance shows circadian oscillation.


2021 ◽  
pp. ASN.2020091319
Author(s):  
Shanmugakumar Chinnappa ◽  
Nigel Lewis ◽  
Omer Baldo ◽  
Ming-Chieh Shih ◽  
Yu-Kang Tu ◽  
...  

Background Impaired exercise capacity is a significant symptom of CKD and is associated with poor survival. Furthermore, there is a growing interest in applying exercise as a diagnostic tool or as therapy in CKD. However, an in-depth understanding of exercise physiology in CKD is still lacking. Methods To evaluate the role of cardiac (central) and noncardiac (peripheral) determinants of exercise capacity in CKD, we conducted a cross-sectional study of 70 male CKD patients (stages 2-5) without diabetes or cardiac disease, 35 healthy controls, and 25 patients with heart failure. An integrated cardiopulmonary exercise test using a CO2 rebreathing technique was used to measure peak O2 consumption (VO2peak) and peak cardiac output simultaneously, and to calculate peak peripheral O2 extraction [C(a-v)O2], the peripheral determinant (the ability of exercising skeletal muscles to extract oxygen). We performed multiple regression analysis and used Bayesian information criteria (BIC) changes to quantitatively assess the individual contribution of central and peripheral factors. Results Compared with healthy controls, in patients with CKD, the VO2peak was impaired proportionate to its severity. Peak cardiac output was the predominant determinant of VO2peak in healthy controls and patients with heart failure, whereas C(a-v)O2 played a more significant role in determining VO2peak in CKD (β=0.68, P<0.001) compared with cardiac output (β=0.63, P<0.001). In addition, the magnitude of BIC reduction was greater for C(a v)O2 compared with cardiac output (BIC, 298.72 versus 287.68) in CKD. Conclusions In CKD, both peak cardiac output and peak C(a-v)O2 are independent predictors of VO2peak, and the more significant role played by peak C(a-v)O2 highlights the importance of noncardiac factors in determining exercise capacity in CKD.


2020 ◽  
Vol 82 (1) ◽  
pp. 79-101 ◽  
Author(s):  
Jianhua Zhang ◽  
John C. Chatham ◽  
Martin E. Young

On Earth, all life is exposed to dramatic changes in the environment over the course of the day; consequently, organisms have evolved strategies to both adapt to and anticipate these 24-h oscillations. As a result, time of day is a major regulator of mammalian physiology and processes, including transcription, signaling, metabolism, and muscle contraction, all of which oscillate over the course of the day. In particular, the heart is subject to wide fluctuations in energetic demand throughout the day as a result of waking, physical activity, and food intake patterns. Daily rhythms in cardiovascular function ensure that increased delivery of oxygen, nutrients, and endocrine factors to organs during the active period and the removal of metabolic by-products are in balance. Failure to maintain these physiologic rhythms invariably has pathologic consequences. This review highlights rhythms that underpin cardiac physiology. More specifically, we summarize the key aspects of cardiac physiology that oscillate over the course of the day and discuss potential mechanisms that regulate these 24-h rhythms.


2020 ◽  
Vol 129 (1) ◽  
pp. 49-57
Author(s):  
Benton S. Purnell ◽  
Gordon F. Buchanan

It has long been appreciated that breathing is altered by time of day. This study demonstrates that rhythmicity in breathing persists in constant darkness but is dependent on the suprachiasmatic nucleus in the hypothalamus. Understanding circadian rhythms in breathing may be important for the treatment and prevention of diseases such as sleep apnea and sudden unexpected death in epilepsy.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S402-S403
Author(s):  
Christopher N Kaufmann ◽  
Katie L Stone

Abstract As the US population ages, the prevalence of Alzheimer’s Disease (AD) and related dementias is expected to increase, making dementia prevention efforts a major public health priority. Impaired sleep and circadian rhythms, along with other lifestyle factors, have emerged as important modifiable disease risk factors—recent studies demonstrate the importance of sleep in preventing the development of key biomarkers for AD/dementia pathology. In this symposium, we will highlight findings on the associations of sleep, circadian rhythm disruptions, and daytime activity patterns on development of cognitive decline and dementia, exploring not only the mechanisms driving these associations, but the potential impact of sleep and lifestyle interventions in promoting healthy brain aging. The symposium consists of four presentations which use data from large national cohort studies. First, we will present analyses on patterns of 24-hour (circadian) activity rhythms (e.g., usual time of day for peak activity, regularity of circadian patterns) and incident dementia risk. The second presentation will present findings pertaining to understanding the link between sleep disturbance and inflammation (a substantial contributor to cognitive aging). The third will examine whether detailed daytime activity patterns associate with imaging-based brain volumes, independent of sleep disturbance. The final presentation will explore whether initiation of sleep disorder treatments may have the potential to change trajectories of cognitive performance as individuals age. Overall, the symposium will highlight the importance of sleep and activity patterns to brain health and stimulate discussion about improving sleep and circadian disruption as a target for dementia prevention efforts.


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