Transcription of biological aging markers (ANRIL, P16ink4a, TBX2, and TERRA) and their correlations with severity of sulfur mustard exposure in veterans

Abstract

Sulfur mustard (SM) exposure has delayed harmful effects, including cell senescence and premature biological aging. This study aimed to evaluate the expression of four main markers of biological aging (i.e., ANRIL, P16ink4a, TBX2, and TERRA) and assess their correlation with the severity of SM exposure in the long term. The study was conducted on two groups of volunteers. 1) the SM-exposed group, exposed to SM once in 1987 during the Iraq-Iran war. This group was divided into three subgroups based on the injury severity, asymptom (exposure to SM without any clinical signs), mild, and severe subgroups; 2) the non-exposed group. ANRIL and TBX2 transcripts were reduced in the total SM-exposed people. Their reduction was more considerable in the SM-exposed subgroups of mild and severe. On the other hand, P16ink4a and TERRA transcripts were increased due to SM exposure. The increase of TERRA expression was more significant in the asymptom, mild and severe subgroups, while P16ink4a was only higher in the asymptom subgroup. There was a positive correlation between the TERRA transcript and the severity of injury, while this correlation was negative for the ANRIL transcript. Thus, the delayed toxicity of SM is associated with the dysregulation of aging markers leading to progressive premature cellular senescence that is dependent on the severity of SM exposure.