Ma Yi-Shing, Wu Shi-Bei, Lee Wan-Yu, Cheng Ju-San, Wei Yau-Huei
Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Biochim Biophys Acta. 2009 Oct;1790(10):1021-9. doi: 10.1016/j.bbagen.2009.04.012. Epub 2009 May 4.
In the aging process, mitochondrial function gradually declines with an increase of mutations in mitochondrial DNA (mtDNA) in tissue cells. Some of the aging-associated mtDNA mutations have been shown to result in not only inefficient generation of ATP but also increased production of reactive oxygen species (ROS) such as superoxide anions (O2-) and hydrogen peroxide (H2O2) in the mitochondria of aging tissues. Extensive studies have revealed that such an increase of oxidative stress is a contributory factor for alterations in the expression and activities of antioxidant enzymes and increased oxidative damage to DNA, RNA, proteins, and lipids in tissues and cultured cells from elderly subjects. Recently, we observed that gene expression of several proteins and enzymes related to iron metabolism is altered and that aconitase is extremely susceptible to oxidative damage in senescent skin fibroblasts and in cybrids harboring aging-associated A8344G mutation of mtDNA. Of great importance is the perturbation at the protein and activity levels of several enzymes containing iron-sulfur clusters in skin fibroblasts of elderly subjects. Taken together, these findings suggest that cellular response to oxidative stress and oxidative damage elicited by mitochondrial dysfunction and/or mtDNA mutations plays an important role in human aging.
在衰老过程中，随着组织细胞中线粒体DNA（mtDNA）突变的增加，线粒体功能逐渐衰退。一些与衰老相关的mtDNA突变不仅会导致ATP生成效率低下，还会使衰老组织的线粒体中活性氧（ROS）如超氧阴离子（O2-）和过氧化氢（H2O2）的产生增加。广泛的研究表明，这种氧化应激的增加是导致老年受试者组织和培养细胞中抗氧化酶表达和活性改变以及对DNA、RNA、蛋白质和脂质氧化损伤增加的一个促成因素。最近，我们观察到衰老皮肤成纤维细胞和携带与衰老相关的mtDNA A8344G突变的胞质杂种中铁代谢相关的几种蛋白质和酶的基因表达发生了改变，并且乌头酸酶极易受到氧化损伤。非常重要的是，老年受试者皮肤成纤维细胞中几种含铁硫簇的酶在蛋白质和活性水平上受到了干扰。综上所述，这些发现表明细胞对线粒体功能障碍和/或mtDNA突变引发的氧化应激和氧化损伤的反应在人类衰老过程中起着重要作用。
