Accelerated senescence in sulfur mustard-exposed individuals: Evidence from oxidative DNA damage, telomere shortening, and dietary inflammatory index.

SM-exposed veterans exhibited shorter leukocyte telomere lengths compared to healthy controls, indicating accelerated cellular aging.

• Leukocyte telomere length (LTL) was assessed using MMqPCR (multiplex monochrome quantitative PCR).
• Telomere shortening was observed across all SM-exposed subgroups (asthma, bronchial obliterans, and chronic bronchitis-like).
• The mustard lung (ML) group showed higher Dietary Inflammatory Index (DII) scores that correlated with shorter telomeres.
• Variations in telomere shortening were noted among subgroups and could assist in distinguishing between asthma, BO, and CB clinical presentations.

SM-exposed veterans showed elevated oxidative DNA damage as measured by 8-oxo-dG levels compared to controls.

• Oxidative DNA damage was measured via ELISA quantification of 8-oxo-dG (8-oxo-2'-deoxyguanosine).
• Elevated 8-oxo-dG levels were observed in SM-exposed veterans relative to healthy controls.
• Variations in 8-oxo-dG levels were present among clinical subgroups (asthma, BO, CB-like), suggesting these levels can indicate disease severity.
• 8-oxo-dG level variations along with telomere shortening can assist in distinguishing between corresponding asthma, BO, and CB subgroups.

OGG1 gene expression was upregulated in SM-exposed veterans, reflecting a response to oxidative DNA damage.

• OGG1 (8-oxoguanine DNA glycosylase 1) gene expression was measured by quantitative PCR (q-PCR).
• Upregulated OGG1 expression was observed in SM-exposed veterans compared to controls.
• OGG1 upregulation reflects the cellular response to elevated oxidative DNA damage (8-oxo-dG).
• OGG1 expression was identified as a marker of SM-induced damage alongside telomere shortening and p16 expression.

p16 gene expression was higher in SM-exposed veterans compared to healthy controls, indicating accelerated cellular senescence.

• p16 (CDKN2A) gene expression was measured by q-PCR as a marker of cellular senescence.
• Higher p16 expression was found in SM-exposed veterans relative to healthy controls.
• The ML group's higher DII scores correlated with increased p16 expression in addition to shorter telomeres.
• p16 expression was identified as a senescence marker signifying SM-induced damage.

The mustard lung group had higher Dietary Inflammatory Index scores that correlated with shorter telomeres and increased p16 expression.

• DII was calculated from dietary intake data collected from SM-exposed veterans and controls.
• Higher DII scores in the ML group indicate more pro-inflammatory dietary patterns.
• Pro-inflammatory dietary patterns correlated with shorter telomeres and increased p16 expression in the ML group.
• These findings suggest that pro-inflammatory diet combined with SM exposure synergistically accelerates cellular aging.

Asthma, bronchial obliterans, and chronic bronchitis-like subgroups shared similar trends in senescence markers but showed variations in oxidative damage and telomere shortening.

• Veterans were clinically categorized based on severity and resemblance to chronic bronchitis (CB), bronchial obliterans (BO), or asthma.
• All three subgroups demonstrated trends of shorter telomeres, higher p16 expression, elevated 8-oxo-dG, and upregulated OGG1 compared to controls.
• Variations in oxidative damage (8-oxo-dG levels) and telomere shortening existed among the three clinical subgroups.
• These differential patterns of 8-oxo-dG and telomere shortening can assist in distinguishing between asthma, BO, and CB clinical presentations.