Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
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DOI：
10.1126/science.1112125
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发表时间：
2005-07-15
期刊：
影响因子：
56.9
通讯作者：
Prolla, TA
中科院分区：
文献类型：
--
作者：
Kujoth, GC;Hiona, A;Prolla, TA
线粒体DNA（mtDNA）突变在哺乳动物组织中积累，并且被假设与衰老有关。我们发现，表达一种缺乏校对功能的线粒体DNA聚合酶γ（POLG）的小鼠会积累mtDNA突变，并表现出加速衰老的特征。mtDNA突变的积累与氧化应激标志物增加或细胞增殖缺陷无关，但与凋亡标志物的诱导相关，特别是在细胞更新快的组织中。在正常小鼠衰老过程中也发现凋亡标志物水平增加。因此，促进细胞凋亡的mtDNA突变积累可能是驱动哺乳动物衰老的核心机制。
Mutations in mitochondrial DNA. (mtDNA) accumulate in tissues of mammalian species and have been hypothesized to contribute to aging. We show that mice expressing a proof reading-deficient version of the mitochondrial DNA polymerase gamma (POLG) accumulate mtDNA mutations and display features of accelerated aging. Accumulation of mtDNA mutations was not associated with increased markers of oxidative stress or a defect in cellular proliferation, but was correlated with the induction of apoptotic markers, particularly in tissues characterized by rapid cellular turnover. The levels of apoptotic markers were also found to increase during aging in normal mice. Thus, accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging.