Nguyen HVM, Hu F, Shakya E, Fender C, Lee K, Schindler J, Garcia-Jaramillo M, Ahsan N, et al. 2026. Mitochondrial-haplotype influences plasma metabolome, lipidome, and proteome in a sex specific manner in the genetically heterogenous OKC-HETB/W rat. FASEB J 40(10):e71736; doi: 10.1096/fj.202502189RRR. PMID: 42171346.
Abstract
The effect of mitochondrial-haplotype (mt-haplotype) on aging was studied using a unique rat model (OKC-HETB/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-HETB/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-HETB or OKC-HETW 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.