Identification of two patterns of mitochondrial DNA-copy number variation in postcentral gyrus during aging, influenced by body mass index and type 2 diabetes.

Abstract

Mitochondrial (mt) DNA replication is strongly associated with oxidative stress, a condition triggered by aging and hyperglycemia, both of which contribute to mitophagy disruption and inflammation. This observational exploratory study evaluated mtDNA-copy number (mtDNA-CN) and expression of genes involved in mitochondriogenesis (PPARGC1A, TFAM, TFB1M, TFB2M), mitophagy (PINK1, PRKN), and inflammatory pathways triggered by hyperglycemia (TXNIP, NLRP3, NFKB1), in the postcentral gyrus of adults and older individuals with and without type 2 diabetes mellitus (T2D). Quantitative real-time PCR was employed to evaluate mtDNA-CN and gene expression; tissue autofluorescence, a marker of aging and of cells with damaged organelles, was also quantified. No correlation was found between age and mtDNA-CN, but a direct correlation was observed for cases with mtDNA-CN >1000 (r=0.41). The mtDNA-CN >1000 group had greater tissue autofluorescence and higher body mass index compared to the mtDNA-CN <1000 group (BMI; 25.7 vs 22.0kg/m2, respectively). mtDNA-CN correlated with tissue autofluorescence in the overall sample (r=0.55) and in the T2D group (r=0.64). PINK and PRKN expressions were inversely correlated with age. Mitochondriogenesis genes and TXNIP expressions were higher in the T2D group, and correlations among the mitochondriogenesis genes were also stronger in this group, relative to the subgroup with mtDNA-CN >1000.