论文标题
外围钟的最小模型揭示了在衰老中的差异昼夜节律重新进入
A minimal model of peripheral clocks reveals differential circadian re-entrainment in aging
论文作者
论文摘要
哺乳动物的昼夜节律系统包括一个细胞自主振荡器网络，从大脑的中央时钟到其他器官的外围钟。这些时钟紧密地协调以编排有节奏的生理和行为功能。这些节奏的失调是衰老的标志，但尚不清楚与年龄相关的变化如何导致更容易破坏的昼夜节律。使用集成了中间时钟和外围时钟的耦合振荡器的两个构图模型，我们得出了简单的平均场方程，可以捕获哺乳动物昼夜节律系统中发现的丰富行为的许多方面。我们专注于三种与年龄相关的效应，这些效应已被认为是导致昼夜节律未对准的：从交感神经途径中减弱的输入，对光的反应性降低以及神经递质表达的下降。我们发现，前两个因素可能会严重阻碍扰动后时钟的重新排列，而中央时钟内的耦合较弱不会影响恢复速率。此外，使用我们的最小模型，我们证明了使用饲料快速周期作为有效干预措施加速昼夜节律的潜力。这些结果强调了外围时钟在调节昼夜节律方面的重要性，并提供了有关衰老和昼夜节律弹性之间复杂相互作用的新见解。
The mammalian circadian system comprises a network of cell-autonomous 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 which 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 a 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.
