Department of Biology, Concordia University, Montreal, Quebec, Canada.
Exp Gerontol. 2009 Sep;44(9):555-71. doi: 10.1016/j.exger.2009.06.001. Epub 2009 Jun 17.
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.
衰老是一个高度复杂的、多因素的过程。我们使用酵母酿酒酵母作为模型来研究多细胞真核生物细胞衰老的机制。为了从系统的角度解决衰老的固有复杂性，并构建衰老过程的综合模型，我们研究了热量限制（CR），即低热量饮食方案，对衰老酵母的代谢历史的影响。我们研究了 CR 如何影响细胞内许多蛋白质和代谢物水平、碳水化合物和脂质代谢、细胞器间代谢流、活性氧浓度、线粒体形态、线粒体中重要的氧化还原过程、线粒体蛋白质组、线粒体内膜中的心磷脂、线粒体 DNA 突变的频率、线粒体核小体的动力学、对线粒体控制的细胞凋亡的敏感性以及抗应激能力的年龄相关动态变化。通过比较长寿 CR 酵母和短寿非 CR 酵母的代谢历史，我们提出酵母在生殖成熟之前，通过设计特定于饮食的代谢和细胞器动态模式来定义它们的长期生存能力。因此，我们的数据表明，在经历时间的酵母中，寿命是由它们在进入非增殖状态之前以特定于饮食的方式发展的代谢能力和细胞器组织水平编程的。
