The mammalian circadian system comprises a network of endogenous oscillators, spanning from the central clock in the brain to peripheral clocks in other organs. These clocks are tightly coordinated to orchestrate rhythmic physiological and behavioral functions. Dysregulation of these rhythms is a hallmark of aging, yet it remains unclear how age-related changes lead to more easily disrupted circadian rhythms. Using a two-population model of coupled oscillators that integrates the central clock and the peripheral clocks, we derive simple mean-field equations that can capture many aspects of the rich behavior found in the mammalian circadian system. We focus on three age-associated effects that have been posited to contribute to circadian misalignment: attenuated input from the sympathetic pathway, reduced responsiveness to light, and a decline in the expression of neurotransmitters. We find that the first two factors can significantly impede re-entrainment of the clocks following perturbation, while a weaker coupling within the central clock does not affect the recovery rate. Moreover, using our minimal model, we demonstrate the potential of using the feed–fast cycle as an effective intervention to accelerate circadian re-entrainment. These results highlight the importance of peripheral clocks in regulating the circadian rhythm and provide fresh insights into the complex interplay between aging and the resilience of the circadian system.
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A minimal model of peripheral clocks reveals differential circadian re-entrainment in aging
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September 2023
Research Article|
September 05 2023
A minimal model of peripheral clocks reveals differential circadian re-entrainment in aging
Yitong Huang
;
Yitong Huang
a)
(Conceptualization, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing)
1
Department of Molecular Biosciences, Northwestern University
, Evanston, Illinois 60208, USA
2
NSF-Simons Center for Quantitative Biology, Northwestern University
, Evanston, Illinois 60208, USA
a)Author to whom correspondence should be addressed: yitong.huang@northwestern.edu
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Yuanzhao Zhang
;
Yuanzhao Zhang
(Formal analysis, Investigation, Methodology, Writing – review & editing)
3
Santa Fe Institute
, 1399 Hyde Park Road, Santa Fe, New Mexico 87501, USA
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Rosemary Braun
Rosemary Braun
b)
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Writing – review & editing)
1
Department of Molecular Biosciences, Northwestern University
, Evanston, Illinois 60208, USA
2
NSF-Simons Center for Quantitative Biology, Northwestern University
, Evanston, Illinois 60208, USA
3
Santa Fe Institute
, 1399 Hyde Park Road, Santa Fe, New Mexico 87501, USA
4
Department of Engineering Sciences and Applied Mathematics, Northwestern University
, Evanston, Illinois 60208, USA
5
Department of Physics and Astronomy, Northwestern University
, Evanston, Illinois 60208, USA
6
Northwestern Institute on Complex Systems, Northwestern University
, Evanston, Illinois 60208, USA
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a)Author to whom correspondence should be addressed: yitong.huang@northwestern.edu
b)
Electronic mail: rbraun@northwestern.edu
Chaos 33, 093104 (2023)
Article history
Received:
May 08 2023
Accepted:
July 27 2023
Citation
Yitong Huang, Yuanzhao Zhang, Rosemary Braun; A minimal model of peripheral clocks reveals differential circadian re-entrainment in aging. Chaos 1 September 2023; 33 (9): 093104. https://doi.org/10.1063/5.0157524
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