Exposure to benzene, toluene and xylenes (BTX) and biological aging: epidemiological evidence from Chinese industrial workers and mechanistic insights.

Higher urinary benzene metabolite SPMA was significantly associated with greater biological age acceleration.

• β = 0.15, 95% CI: 0.07 to 0.24 in fully adjusted models
• SPMA (S-phenylmercapturic acid) is a urinary metabolite of benzene
• Biological age acceleration (KDM-BA.Accel) was defined as biological age minus chronological age
• Biological age was estimated using the Klemera-Doubal method (KDM) from clinical biomarkers

Higher urinary benzene metabolite TTMA was significantly associated with greater biological age acceleration.

• β = 0.08, 95% CI: 0.01 to 0.14 in fully adjusted models
• TTMA (trans,trans-muconic acid) is a urinary metabolite of benzene
• Association was smaller in magnitude than that observed for SPMA
• Both SPMA and TTMA were creatinine-adjusted prior to analysis

Xylene metabolites also showed positive associations with biological age acceleration.

• Xylene metabolites included 2-methylhippuric acid (2MHA) and 3-/4-methylhippuric acids (3&4MHA)
• Associations were positive in fully adjusted generalized linear models
• Specific beta coefficients and confidence intervals for xylene metabolites are not reported in the abstract
• Creatinine-adjusted urinary metabolites were used in all analyses

Bayesian kernel machine regression (BKMR) indicated a positive overall association of the BTX mixture with biological age acceleration, with benzene biomarkers contributing most.

• BKMR was used to assess mixture associations of all BTX metabolites simultaneously
• SPMA and TTMA contributed most prominently to the overall mixture association
• Mixture included five urinary metabolites: SPMA, TTMA, SBMA (toluene), 2MHA, and 3&4MHA (xylenes)
• SBMA (S-benzylmercapturic acid) is a toluene metabolite also included in the mixture model

The study enrolled 301 BTX-exposed workers and 741 unexposed controls, with 301 matched controls selected using 1:1 propensity score matching.

• Study conducted in Henan, China, 2022–2023
• Propensity score matching was used to reduce confounding between exposed and control groups
• Final matched analysis included 301 exposed workers and 301 matched controls
• BTX refers to benzene, toluene, and xylenes, which are common workplace volatile organic compounds

Network toxicology analyses prioritized eight hub genes potentially linking BTX exposure to biological aging.

• The eight hub genes identified were TP53, TNF, NFKB1, TGFB1, MAPK3, CTNNB1, FOS, and JUN
• Enrichment analyses were consistent with oxidative stress response, inflammatory signaling, and cell-cycle regulation pathways
• Molecular docking was also performed as part of the computational analyses
• Computational analyses were used to explore biological plausibility of the observed associations