# Reduction in mitochondrial DNA methylation leads to compensatory increase in mitochondrial DNA content: novel blood-borne biomarkers for monitoring occupational noise

## TL;DR

This study finds that occupational noise exposure reduces mitochondrial DNA methylation, leading to increased mitochondrial DNA content, which could serve as a biomarker for monitoring noise-related health risks.

## Contribution

The study identifies MT-RNR1 methylation and mitochondrial DNA content as novel biomarkers for occupational noise exposure.

## Key findings

- Workers with abnormal hearing had a 4.52% reduction in MT-RNR1 methylation.
- MtDNA copy number increased by 10.75 units in workers with abnormal hearing, partially mediated by MT-RNR1 methylation.
- No significant changes in D-loop methylation were observed.

## Abstract

Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear.

We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing.

There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: −7.43% to −1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = −2.06%, 95% CI: −4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = −0.95, 95% CI: −1.23 to −0.66), while no significant link was found with D-loop methylation (β = −0.05, 95% CI: −0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect.

These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.

The online version contains supplementary material available at https://doi.org/10.1265/ehpm.25-00006.