Mitophagy-Related Gene Dysregulation: Links With Telomere Attrition and Impaired Lung Function in Sulfur Mustard-Exposed Veterans.

Sulfur mustard (SM) exposure in veterans accelerates aging and causes persistent lung function decline. This study tested the hypothesis that dysregulated mitophagy is associated with telomere attrition and SM-induced respiratory impairment. This analysis included 200 participants from a cohort study. Leukocyte telomere length was measured using monochrome multiplex quantitative PCR. Transcriptional expression of mitophagy-related genes (DRP1, FIS1, PINK1, PRKN) was quantified by RT-qPCR. Lung function was assessed by spirometry, measuring forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The SM-exposed group exhibited significantly shorter telomere length, upregulated mitophagy-related gene expression, and reduced FVC and FEV1 compared to controls. After false discovery rate correction, significant negative associations were observed between telomere length and the mitophagy-related genes DRP1, FIS1, and PRKN. Telomere length also showed positive correlations with FVC and FEV1. Furthermore, the expression of DRP1, FIS1, and PRKN was negatively correlated with spirometry parameters. Delayed SM toxicity induces concurrent mitophagy-related gene dysregulation, telomere shortening, and lung function decline. The strong correlations between these transcriptional findings suggest that disrupted mitochondrial quality control may be associated with accelerated cellular aging and respiratory impairment, although functional mitophagy flux was not directly assessed. These results identify the mitophagy-telomere axis as a potential therapeutic target for mitigating SM-related pathology.