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

TL;DR

This study shows that mitochondrial DNA differences affect aging in old rats, and these effects are largely influenced by the sex of the rats.

Contribution

The study is the first to demonstrate that mitochondrial haplotype differences in aging are largely sex dependent.

Findings

50% to 80% of age-related changes in metabolites, lipids, and proteins were specific to mitochondrial haplotype.

78-93% of haplotype-specific changes were also sex specific, occurring in only one sex.

The findings highlight the importance of considering both mitochondrial DNA and sex in aging research.

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.