Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae.
Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae.
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DOI：
10.15698/mic2014.06.152
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发表时间：
2014-05-27
期刊：
影响因子：
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通讯作者：
Titorenko VI
中科院分区：
文献类型：
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作者：
Arlia-Ciommo A;Leonov A;Piano A;Svistkova V;Titorenko VI
大量证据支持这一观点，即控制细胞衰老的信号通路以及通过延长寿命的遗传、饮食和药物干预对其进行调节的机制在物种间是保守的。本综述的范围是批判性地分析我们对芽殖酵母酿酒酵母随时间老化的细胞自主机制的理解的最新进展。根据我们的分析，我们提出了酵母细胞衰老年表基础的生物分子网络的概念。这个概念假设这样的网络会经历一系列的生命周期检查点。在每个检查点，某些代谢途径的一些关键中间体和产物的细胞内浓度，以及这些代谢物在复杂的室间通讯网络中协调流动的速率，都受到一些检查点特异性“主调节器”蛋白质的监测。该概念设想这些主调节蛋白在某些生命早期和生命晚期检查点的协同作用调节细胞代谢、生长、增殖、应激抵抗、大分子稳态、生存和死亡等过程的进展速率和效率。该概念预测，通过在整个生命周期（即细胞生长和分裂停滞之前以及细胞生长和分裂停滞之后）调节这些重要的细胞过程，检查点特异性主调节蛋白协调促衰老或抗衰老细胞模式的发展和维持，从而定义了按时间顺序衰老的酵母的寿命。
A body of evidence supports the view that the signaling pathways governing cellular aging - as well as mechanisms of their modulation by longevity-extending genetic, dietary and pharmacological interventions - are conserved across species. The scope of this review is to critically analyze recent advances in our understanding of cell-autonomous mechanisms of chronological aging in the budding yeast Saccharomyces cerevisiae. Based on our analysis, we propose a concept of a biomolecular network underlying the chronology of cellular aging in yeast. The concept posits that such network progresses through a series of lifespan checkpoints. At each of these checkpoints, the intracellular concentrations of some key intermediates and products of certain metabolic pathways - as well as the rates of coordinated flow of such metabolites within an intricate network of intercompartmental communications - are monitored by some checkpoint-specific ʺmaster regulatorʺ proteins. The concept envisions that a synergistic action of these master regulator proteins at certain early-life and late-life checkpoints modulates the rates and efficiencies of progression of such processes as cell metabolism, growth, proliferation, stress resistance, macromolecular homeostasis, survival and death. The concept predicts that, by modulating these vital cellular processes throughout lifespan (i.e., prior to an arrest of cell growth and division, and following such arrest), the checkpoint-specific master regulator proteins orchestrate the development and maintenance of a pro- or anti-aging cellular pattern and, thus, define longevity of chronologically aging yeast.