Mitochondrial DNA affects metabolome, lipidome, and proteome in a sex specific manner in old heterogenous rats

Abstract The effect of mitochondria-haplotype (mt-haplotype) on aging was studied using a unique rat model (OKC-HETB/W), which has a heterogenous nuclear background and mitochondria from either Brown Norway (B-haplotype) or Wistar Kyoto (W-haplotype) rats that differ in 94 nucleotides. The impact of mt-haplotype on aging was studied using an unbiased multi-omics approach to analyze the plasma from 9- and 26-month-old male and female OKC-HETB/W rats. Of the 280 metabolites, 961 lipids, and 230 proteins that changed significantly with age, 50% to 80% were mt-haplotype specific, occurring in either OKC-HETB or OKC-HETW rats. Interesting, the majority (78-93%) of the changes that were mt-haplotype specific were also sex specific, occurring in either male or female rats but not both. Our data are the first to show the potential importance of mt-haplotype in aging and that this mt-haplotype difference is largely sex dependent.