Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
Sci Rep. 2024 Jul 5;14(1):15479. doi: 10.1038/s41598-024-66347-9.
Most organisms possess three biological oscillators, circadian clock, cell cycle, and redox rhythm, which are autonomous but interact each other. However, whether their interactions and autonomy are beneficial for organisms remains unclear. Here, we modeled a coupled oscillator system where each oscillator affected the phase of the other oscillators. We found that multiple types of coupling prevent a high HO level in cells at M phase. Consequently, we hypothesized a high HO sensitivity at the M phase and found that moderate coupling reduced cell damage due to oxidative stress by generating appropriate phase relationships between three rhythms, whereas strong coupling resulted in an elevated cell damage by increasing the average HO level and disrupted the cell cycle. Furthermore, the multicellularity model revealed that phase variations among cells confer flexibility in synchronization with environments at the expense of adaptability to the optimal environment. Thus, both autonomy and synchrony among the oscillators are important for coordinating their phase relationships to minimize oxidative stress, and couplings balance them depending on environments.
大多数生物都拥有三个生物钟，即昼夜节律钟、细胞周期钟和氧化还原节律钟，它们具有自主性，但又相互作用。然而，它们的相互作用和自主性是否对生物有益尚不清楚。在这里，我们构建了一个耦合振荡器系统，其中每个振荡器影响其他振荡器的相位。我们发现，多种类型的耦合可以防止细胞在 M 期出现高 HO 水平。因此，我们假设 M 期 HO 敏感性较高，并发现适度的耦合通过在三个节律之间产生适当的相位关系来减轻氧化应激引起的细胞损伤，而强耦合则通过增加平均 HO 水平和破坏细胞周期导致细胞损伤增加。此外，多细胞模型表明，细胞之间的相位变化以牺牲对最佳环境的适应性为代价，赋予了与环境同步的灵活性。因此，振荡器之间的自主性和同步性对于协调它们的相位关系以最小化氧化应激都很重要，而耦合则根据环境来平衡它们。
