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

Sulfur mustard (SM) exposure induces respiratory complications, known as "mustard lung (ML)" through oxidative stress and chronic inflammation. This study investigated premature cellular senescence as a marker of systemic aging in SM-exposed veterans with serious pulmonary conditions, focusing on oxidative stress, DNA damage, telomere shortening, and OGG1/p16 gene expression, as well as the role of pro-inflammatory dietary patterns measured by the Dietary Inflammatory Index (DII). The study included SM-exposed veterans and healthy controls. Veterans were clinically categorized based on severity and resemblance to chronic bronchitis (CB), bronchial obliterans (BO), or asthma. Leukocyte telomere length (LTL) was assessed using MMqPCR, oxidative DNA damage (8-oxo-dG) via ELISA, and OGG1/p16 gene expression by q-PCR. DII was calculated from dietary intake data. Compared to controls, SM-exposed veterans exhibited shorter telomeres, higher p16 expression, elevated 8-oxo-dG levels, and upregulated OGG1 expression, reflecting accelerated aging and oxidative DNA damage. Asthma, BO, and CB-like subgroups shared similar trends, with variations in oxidative damage and telomere shortening. The ML group had higher DII scores correlated with shorter telomeres and increased p16 expression. These findings suggest that SM exposure, coupled with pro-inflammatory dietary patterns, accelerates cellular aging through oxidative damage and inflammation. Markers such as telomere shortening, OGG1, and p16 expression signify SM-induced damage, while 8-oxo-dG levels can indicate disease severity. In addition, variations in 8-oxo-dG levels and telomere shortening can assist in distinguishing between corresponding asthma, BO, and CB. Ultimately, this study underscores the importance of targeted interventions, including dietary modifications, to mitigate the long-term effects of SM exposure and improve outcomes for affected individuals.