Enhanced cellular longevity arising from environmental fluctuations.

Yuting Liu, Zhen Zhou, Hetian Su, Songlin Wu, Gavin Ni, Alex Zhang, Lev S Tsimring, Jeff Hasty, Nan Hao
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Abstract

Cellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions but also revealed the theoretical principles underlying these interventions. We introduce the dynamical systems theory to capture two general means for promoting longevity-the creation of a stable fixed point in the "healthy" state of the cell and the "dynamic stabilization" of the system around this healthy state through environmental oscillations. Guided by the model, we investigate how both of these can be experimentally realized by dynamically modulating environmental glucose levels. The results establish a paradigm for theoretically analyzing the trajectories and perturbations of aging that can be generalized to aging processes in diverse cell types and organisms.

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环境波动导致细胞寿命延长。
细胞寿命受遗传和环境因素的调节。然而,这些因素在衰老过程中的相互作用在很大程度上仍不清楚。在这里,我们建立了一个数学模型,用于对酵母衰老过程中的核心基因回路进行动态葡萄糖调节,该模型不仅指导了促长寿干预措施的设计,还揭示了这些干预措施的理论基础。我们引入了动力系统理论来捕捉促进长寿的两种一般手段--在细胞的 "健康 "状态下创建一个稳定的固定点,以及通过环境振荡使系统围绕这一健康状态实现 "动态稳定"。在该模型的指导下,我们研究了如何通过动态调节环境中的葡萄糖水平在实验中实现这两种方法。研究结果为从理论上分析衰老的轨迹和扰动建立了一个范例,该范例可推广到不同细胞类型和生物体的衰老过程中。
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