SYSBIO Centre for Systems Biology, Milano, Italy; Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.
Int Rev Cell Mol Biol. 2018;340:1-33. doi: 10.1016/bs.ircmb.2018.05.001. Epub 2018 Jun 19.
Mitochondrial functionality is one of the main factors involved in cell survival, and mitochondrial dysfunctions have been identified as an aging hallmark. In particular, the insurgence of mitochondrial dysfunctions is tightly connected to mitochondrial metabolism. During aging, both mitochondrial oxidative and biosynthetic metabolisms are progressively altered, with the development of malfunctions, in turn affecting mitochondrial functionality. In this context, the relation between mitochondrial pathways and aging is evolutionarily conserved from single-celled organisms, such as yeasts, to complex multicellular organisms, such as humans. Useful information has been provided by the yeast Saccharomyces cerevisiae, which is being increasingly acknowledged as a valuable model system to uncover mechanisms underlying cellular longevity in humans. On this basis, we review the impact of specific aspects of mitochondrial metabolism on aging supported by the contributions brought by numerous studies performed employing yeast. Initially, we will focus on the tricarboxylic acid cycle and oxidative phosphorylation, describing how their modulation has consequences on cellular longevity. Afterward, we will report information regarding the importance of nicotinamide adenine dinucleotide (NAD) metabolism during aging, highlighting its relation with mitochondrial functionality. The comprehension of these key points regarding mitochondrial metabolism and their physiological importance is an essential first step for the development of therapeutic interventions that point to increase life quality during aging, therefore promoting "healthy aging," as well as lifespan itself.
线粒体功能是细胞存活的主要因素之一，线粒体功能障碍已被确定为衰老的一个标志。特别是，线粒体功能障碍的出现与线粒体代谢紧密相关。随着衰老的进行，线粒体的氧化和生物合成代谢都在逐渐改变，随之而来的是功能障碍的发展，进而影响线粒体功能。在这种情况下，从单细胞生物酵母到复杂的多细胞生物人类，线粒体途径与衰老之间的关系在进化上是保守的。酵母酿酒酵母提供了有用的信息，它正被越来越多地视为揭示人类细胞长寿机制的有价值的模型系统。在此基础上，我们综述了线粒体代谢的特定方面对衰老的影响，这些影响是通过许多在酵母中进行的研究得出的。首先，我们将重点讨论三羧酸循环和氧化磷酸化，描述它们的调节如何对细胞寿命产生影响。之后，我们将报告关于衰老过程中烟酰胺腺嘌呤二核苷酸 (NAD) 代谢重要性的信息，强调其与线粒体功能的关系。理解线粒体代谢的这些关键点及其生理重要性是开发治疗干预措施的重要第一步，这些干预措施旨在提高衰老过程中的生活质量，从而促进“健康衰老”以及寿命本身。
