Effect of calorie restriction on the metabolic history of chronologically aging yeast
Effect of calorie restriction on the metabolic history of chronologically aging yeast
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DOI：
10.1016/j.exger.2009.06.001
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发表时间：
2009-09-01
影响因子：
3.9
通讯作者：
Titorenko, Vladimir I.
中科院分区：
文献类型：
--
作者：
Goldberg, Alexander A.;Bourque, Simon D.;Titorenko, Vladimir I.
衰老是一个高度复杂、多因素的过程。我们以酿酒酵母为模型，研究了多细胞真核生物中细胞衰老的机制。为了从系统的角度解决老化的内在复杂性，并建立老化过程的综合模型，我们研究了低热量饮食方案--热量限制(CR)对按时间顺序老化的酵母代谢历史的影响。我们研究了CR如何影响多种蛋白质和代谢物的细胞内水平、碳水化合物和脂肪代谢、细胞器间代谢流量、活性氧物种浓度、线粒体形态、线粒体基本氧化还原过程、线粒体蛋白质组、线粒体内膜心磷脂、线粒体DNA突变频率、线粒体类核动态、线粒体控制的凋亡易感性和抗逆性的年龄相关动态变化。基于长寿命CR酵母和短寿命非CR酵母的代谢史的比较，我们认为酵母在生殖成熟之前通过设计特定的代谢模式和细胞器动力学来定义其长期生存能力。因此，我们的数据表明，按时间顺序老化的酵母的寿命是由它们在进入非增殖状态之前以特定饮食方式发展起来的代谢能力和细胞器组织的水平决定的。(C)2009 Elsevier Inc.保留所有权利。
Aging is a highly complex, multifactorial process. We use the yeast Saccharomyces cerevisiae as a model to study the mechanisms of cellular aging in multicellular eukaryotes. To address the inherent complexity of aging from a systems perspective and to build an integrative model of aging process, we investigated the effect of calorie restriction (CR), a low-calorie dietary regimen, on the metabolic history of chronologically aging yeast. We examined how CR influences the age-related dynamics of changes in the intracellular levels of numerous proteins and metabolites, carbohydrate and lipid metabolism, interorganellar metabolic flow, concentration of reactive oxygen species, mitochondrial morphology, essential oxidation-reduction processes in mitochondria, mitochondrial proteome, cardiolipin in the inner mitochondrial membrane, frequency of mitochondrial DNA mutations, dynamics of mitochondrial nucleoid, susceptibility to mitochondria-controlled apoptosis, and stress resistance. Based on the comparison of the metabolic histories of long-lived CR yeast and short-lived non-CR yeast, we propose that yeast define their long-term viability by designing a diet-specific pattern of metabolism and organelle dynamics prior to reproductive maturation. Thus, our data suggest that longevity in chronologically aging yeast is programmed by the level of metabolic capacity and organelle organization they developed, in a diet-specific fashion, prior to entry into a non-proliferative state. (C) 2009 Elsevier Inc. All rights reserved.