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 Caenorhabditis elegans. 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.
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