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首页> 外文期刊>The Journal of investigative dermatology. >The relationship between the aging- and photo-dependent T414G mitochondrial DNA mutation with cellular senescence and reactive oxygen species production in cultured skin fibroblasts.
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The relationship between the aging- and photo-dependent T414G mitochondrial DNA mutation with cellular senescence and reactive oxygen species production in cultured skin fibroblasts.

机译：在培养的皮肤成纤维细胞中，年龄依赖性和光依赖性T414G线粒体DNA突变与细胞衰老和活性氧产生之间的关系。

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摘要

Mutations in the mitochondrial genome (mtDNA) are thought to be one of the causes of age-dependent cellular decline through their detrimental effects on respiration or reactive oxygen species (ROS) production. However, for many mutations, this link has not been clearly established. This study aimed to further investigate the phenotypic importance of a T414G mutation within the control region of mtDNA, previously shown to accumulate in both chronologically and photoaged human skin. We demonstrate that during dermal skin fibroblast replication in vitro in five separate cultures obtained from elderly individuals, the T414G mutant load can either increase or decrease during progressive cell division, implying the absence of consistent selection against the mutation in this context. In support of this, by utilizing a cell-sorting approach, we demonstrate that the level of the T414G mutation does not directly correlate with increased or decreased mtDNA copy number, or markers of cellular ageing including lipofuscin accumulation or ROS production. By consequence, the mutation can be distributed with a bias towards either the proliferating or senescent cell populations depending on the cell line. In conclusion, we propose that this particular mutation may have little effect on ROS production and the onset of cellular senescence in cultured fibroblasts.
机译：线粒体基因组（mtDNA）中的突变通过其对呼吸作用或活性氧（ROS）产生的有害作用，被认为是年龄依赖性细胞衰退的原因之一。但是，对于许多突变，尚未明确建立这种联系。这项研究旨在进一步研究mtDNA控制区域内T414G突变的表型重要性，该突变先前已显示在按时间顺序和光老化的人类皮肤中积累。我们证明，在从老年个体获得的五个单独的培养物中，体外皮肤皮肤成纤维细胞复制过程中，T414G突变体的负荷在进行性细胞分裂过程中可以增加或减少，这意味着在这种情况下没有针对突变的一致选择。为此，我们利用细胞分选方法证明了T414G突变的水平与mtDNA拷贝数的增加或减少或包括脂褐素积聚或ROS产生在内的细胞衰老标记不直接相关。结果，取决于细胞系，突变可以偏向增殖细胞或衰老细胞群分布。总之，我们建议这种特定的突变可能对ROS的产生和培养的成纤维细胞中细胞衰老的开始几乎没有影响。

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