Mitochondrial‐Haplotype Influences Plasma Metabolome, Lipidome, and Proteome in a Sex Specific Manner in the Genetically Heterogenous <scp>OKC</scp> ‐ <scp> HET ^B </scp> ^/W Rat

ABSTRACT The effect of mitochondrial‐haplotype (mt‐haplotype) on aging was studied using a unique rat model (OKC‐HET B/W ), which has a heterogenous nuclear background combined with 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‐HET B/W rats. Of the 280 metabolites, 961 lipids, and 230 proteins that were different in each age group, 50%–80% were mt‐haplotype specific, occurring in either OKC‐HET B or OKC‐HET W rats but not both. The majority (78%–93%) of the differences 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.