Department of Genetics, Xuzhou Medical University, Xuzhou, China.
Medical Technology School of Xuzhou Medical University, Xuzhou, China.
Aging (Albany NY). 2020 Feb 4;12(3):2453-2470. doi: 10.18632/aging.102754.
Recently, mitochondrial-nuclear interaction in aging has been widely studied. However, the nuclear genome controlled by natural mitochondrial variations that influence aging has not been comprehensively understood so far. We hypothesized that mitochondrial polymorphisms could play critical roles in the aging process, probably by regulation of the whole-transcriptome expression. Our results showed that mitochondria polymorphisms not only decreased the mitochondrial mass but also miRNA, lncRNA, mRNA, circRNA and metabolite profiles. Furthermore, most genes that are associated with mitochondria show age-related expression features (P = 3.58E-35). We also constructed a differentially expressed circRNA-lncRNA-miRNA-mRNA regulatory network and a ceRNA network affected by the mitochondrial variations. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the genes affected by the mitochondrial variation were enriched in metabolic activity. We finally constructed a multi-level regulatory network with aging which affected by the mitochondrial variation in . The interactions between these genes and metabolites have great values for further aging research. In sum, our findings provide new evidence for understanding the molecular mechanisms of how mitochondria influence aging.
最近，线粒体-核相互作用在衰老过程中的研究已经得到了广泛的关注。然而，目前还没有全面了解到受自然线粒体变异影响的核基因组在衰老过程中所起的作用。我们假设线粒体多态性可能在衰老过程中发挥关键作用，可能通过对全转录组表达的调节。我们的结果表明，线粒体多态性不仅降低了线粒体的质量，还影响了 miRNA、lncRNA、mRNA、circRNA 和代谢物的图谱。此外，大多数与线粒体相关的基因都表现出与年龄相关的表达特征（P = 3.58E-35）。我们还构建了一个差异表达的 circRNA-lncRNA-miRNA-mRNA 调控网络和一个受线粒体变异影响的 ceRNA 网络。此外，京都基因与基因组百科全书通路分析显示，受线粒体变异影响的基因富集在代谢活性中。我们最终构建了一个受线粒体变异影响的多层次衰老调控网络。这些基因与代谢物之间的相互作用对于进一步的衰老研究具有重要价值。总之，我们的研究结果为理解线粒体如何影响衰老的分子机制提供了新的证据。
