Circadian Misalignment and Metabolic Disorders: A Story of Twisted Clocks

Woller, Aurore; Gonze, Didier

doi:10.3390/biology10030207

Cited by 11 publications

(11 citation statements)

References 103 publications

(96 reference statements)

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“…Misalignment occurs as the phase of oscillators in different organs shifts at different rates ( 3 ). Disruption of optimal phase relationships among circadian oscillators, as occurs in jet lag and shift work, has adverse consequences for health ( 4 , 5 ).…”

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confidence: 99%

The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease

Sisson

Bahiru

Manoogian

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The Cryptochrome 1 ( Cry1 )–deficient duper mutant hamster has a short free-running period in constant darkness (τ DD ) and shows large phase shifts in response to brief light pulses. We tested whether this measure of the lability of the circadian phase is a general characteristic of Cry1 -null animals and whether it indicates resistance to jet lag. Upon advance of the light:dark (LD) cycle, both duper hamsters and Cry1 −/− mice re-entrained locomotor rhythms three times as fast as wild types. However, accelerated re-entrainment was dissociated from the amplified phase-response curve (PRC): unlike duper hamsters, Cry1 −/− mice show no amplification of the phase response to 15’ light pulses. Neither the amplified acute shifts nor the increased rate of re-entrainment in duper mutants is due to acceleration of the circadian clock: when mutants drank heavy water to lengthen the period, these aspects of the phenotype persisted. In light of the health consequences of circadian misalignment, we examined effects of duper and phase shifts on a hamster model of heart disease previously shown to be aggravated by repeated phase shifts. The mutation shortened the lifespan of cardiomyopathic hamsters relative to wild types, but this effect was eliminated when mutants experienced 8-h phase shifts every second week, to which they rapidly re-entrained. Our results reveal previously unsuspected roles of Cry1 in phase shifting and longevity in the face of heart disease. The duper mutant offers new opportunities to understand the basis of circadian disruption and jet lag.

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mentioning

confidence: 99%

The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease

Sisson

Bahiru

Manoogian

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Dysregulation of the system through alterations of the timing of zeitgebers (jet lag, shift work, disruptions of feeding time, etc.) can lead to the incidence of a variety of pathologies, including metabolic syndrome, diabetes, obesity, tumorigenesis, and auto-immune disorders ( 74 , 75 ).…”

Section: Discussionmentioning

confidence: 99%

Light-induced synchronization of the SCN coupled oscillators and implications for entraining the HPA axis

Androulakis

2022

Front. Endocrinol.

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The suprachiasmatic nucleus (SCN) synchronizes the physiological rhythms to the external light-dark cycle and tunes the dynamics of circadian rhythms to photoperiod fluctuations. Changes in the neuronal network topologies are suggested to cause adaptation of the SCN in different photoperiods, resulting in the broader phase distribution of neuron activities in long photoperiods (LP) compared to short photoperiods (SP). Regulated by the SCN output, the level of glucocorticoids is elevated in short photoperiod, which is associated with peak disease incidence. The underlying coupling mechanisms of the SCN and the interplay between the SCN and the HPA axis have yet to be fully elucidated. In this work, we propose a mathematical model including a multiple-cellular SCN compartment and the HPA axis to investigate the properties of the circadian timing system under photoperiod changes. Our model predicts that the probability-dependent network is more energy-efficient than the distance-dependent network. Coupling the SCN network by intra-subpopulation and inter-subpopulation forces, we identified the negative correlation between robustness and plasticity of the oscillatory network. The HPA rhythms were predicted to be strongly entrained to the SCN rhythms with a pro-inflammatory high-amplitude glucocorticoid profile under SP. The fast temporal topology switch of the SCN network was predicted to enhance synchronization when the synchronization is not complete. These synchronization and circadian dynamics alterations might govern the seasonal variation of disease incidence and its symptom severity.

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“…Desynchronization of circadian rhythms in ambient environments with periods beyond the entrainment ranges causes decreased adaptation, competence, fitness, growth rate, fertility, and shortened lifespan (López-Otín and Kroemer, 2021;Allada and Bass, 2021;Sharma, 2003;Pittendrigh and Minis, 1972;Mormont et al, 2000). Circadian rhythm is a hallmark of human health (López-Otín and Kroemer, 2021), and circadian misalignment accounts for a variety of diseases, impaired mood (e.g., depression), decreased cognition and performance (Woller and Gonze, 2021;Ma et al, 2019;Guo et al, 2020;Bechtold et al, 2010;Mallis and DeRoshia, 2005). A circadian rhythm with less robust rhythmicity usually possesses a wider entrainment range.…”

Section: Circadian Rhythms and Entrainmentmentioning

confidence: 99%

How to Live on Mars With a Proper Circadian Clock?

Luo

Huang

et al. 2022

Front. Astron. Space Sci.

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Intrinsic circadian clocks generate circadian rhythms of physiology and behavior, which provide the capabilities to adapt to cycling environmental cues that result from the self-rotation of the Earth. Circadian misalignment leads to deleterious impacts on adaptation and health in different organisms. The environmental cues on the interplanetary journey to and on Mars dramatically differ from those on Earth. These differences impose numerous adaptive challenges, including challenges for humans’ circadian clock. Thus, adaptation of circadian rhythms to the Martian environment is a prerequisite for future landing and dwelling on Mars. Here, we review the progress of studies associated with the influence of the Martian environment on circadian rhythms and propose directions for further study and potential strategies to improve the adaptation of the circadian clock for future Mars missions.

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Circadian Misalignment and Metabolic Disorders: A Story of Twisted Clocks

Cited by 11 publications

References 103 publications

The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease

The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease

Light-induced synchronization of the SCN coupled oscillators and implications for entraining the HPA axis

How to Live on Mars With a Proper Circadian Clock?

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