Lee Hsin-Chen, Wei Yau-Huei
Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Exp Biol Med (Maywood). 2007 May;232(5):592-606.
A wide spectrum of alterations in mitochondria and mitochondrial DNA (mtDNA) with aging has been observed in animals and humans. These include (i) decline in mitochondrial respiratory function; (ii) increase in mitochondrial production of reactive oxygen species (ROS) and the extent of oxidative damage to DNA, proteins, and lipids; (iii) accumulation of point mutations and large-scale deletions of mtDNA; and (iv) enhanced apoptosis. Recent studies have provided abundant evidence to substantiate the importance of mitochondrial production of ROS in aging. On the other hand, somatic mtDNA mutations can cause premature aging without increasing ROS production. In this review, we focus on the roles that ROS play in the aging-associated decline of mitochondrial respiratory function, accumulation of mtDNA mutations, apoptosis, and alteration of gene expression profiles. Taking these findings together, we suggest that mitochondrial dysfunction, enhanced oxidative stress, subsequent accumulation of mtDNA mutations, altered expression of a few clusters of genes, and apoptosis are important contributors to human aging.
在动物和人类中，随着衰老，线粒体和线粒体DNA（mtDNA）会出现各种各样的变化。这些变化包括：（i）线粒体呼吸功能下降；（ii）线粒体活性氧（ROS）生成增加以及DNA、蛋白质和脂质的氧化损伤程度增加；（iii）mtDNA点突变和大规模缺失的积累；（iv）细胞凋亡增强。最近的研究提供了大量证据，证实了线粒体产生ROS在衰老过程中的重要性。另一方面，体细胞mtDNA突变可导致早衰，而不增加ROS的产生。在这篇综述中，我们重点关注ROS在与衰老相关的线粒体呼吸功能下降、mtDNA突变积累、细胞凋亡以及基因表达谱改变中所起的作用。综合这些发现，我们认为线粒体功能障碍、氧化应激增强、随后的mtDNA突变积累、少数基因簇表达改变以及细胞凋亡是导致人类衰老的重要因素。
