Sex-specific associations of exposure to metal mixtures with telomere length change: Results from an 8-year longitudinal study

Studies on the relationships between exposure to metal mixtures and telomere length (TL) are limited, particu-larly longitudinal studies. Few studies are available on the potential sex-specific associations between metal ex-posures and TL change. We examined blood metal concentrations and TL at baseline (August 2012) and follow-up (June 2020) among 316 participants in a ferro-manganese refinery. The least absolute shrinkage and selection operator (LASSO) followed by the generalized linear model (GLM) was applied to evaluate the associations be-tween multiple-metal exposures and TL change (TL in 2012 minus TL in 2020). Bayesian kernel machine regres-sion (BKMR) was applied to cope with metal mixtures and evaluate their joint effects on TL change. Among men, three statistical methods consistently showed rubidium was negatively associated with TL change (beta [95% CI] = -2.755 [-5.119, -0.391] in the GLM) and dominated the negative overall effects of 10 metal mixtures (magne-sium, manganese, iron, cobalt, copper, zinc, selenium, rubidium, cadmium, and lead) on TL change (posterior in-clusion probabilities = 0.816). Among women, the GLM (beta [95% CI] = 4.463 [0.943, 7.983]) and LASSO (beta = 4.289) showed rubidium was positively associated with TL change. Interestingly, no significant association was observed between exposure to metal mixtures and TL change in overall participants (P > 0.05). Furthermore, stratified analysis showed significant relationships between rubidium and TL change in men (beta = -2.744), women (3 = 3.624), and current smokers (3 = -3.266) (both P interaction <0.05). In summary, our findings underlined the steady and negative association between rubidium and TL change among men with potential sex-dependent heterogeneities. Further experimental studies are required to expound the underlying mechanisms. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study examined the relationship between exposure to metal mixtures and telomere length change among participants in a ferro-manganese refinery. The results showed a negative association between rubidium exposure and telomere length change in men, and a positive association in women. However, no significant association was observed in overall participants. Stratified analysis further revealed significant relationships between rubidium exposure and telomere length change in men, women, and current smokers. These findings highlight the importance of considering sex-dependent heterogeneities in the association between rubidium exposure and telomere length change.