# 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.

## Key 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.