Individual and joint associations of co-exposure to multiple plasma metals with telomere length among middle-aged and older Chinese in the Dongfeng-Tongji cohort

Studies on associations of metals with leucocyte telomere length (LTL) were mainly limited to several most common toxic metals and single-metal effect, but the impact of other common metals and especially the overall joint associations and interactions of metal mixture with LTL are largely unknown. We included 15 plasma metals and LTL among 4906 participants from Dongfeng-Tongji cohort. Multivariable linear regression was used to estimate associations of individual metals with LTL. We also applied Bayesian kernel machine regression (BKMR) and quantile g-computation regression (Q-g) to evaluate the overall association and interactions, and identified the major contributors as well as the potential modifications by major characteristics. Multivariable linear regression found vanadium, copper, arsenic, aluminum and nickel were negatively associated with LTL, and a 2-fold change was related to 1.9%-5.1% shorter LTL; while manganese and zinc showed 3.7% and 4.0% longer LTL (all P < 0.05) in multiple-metal models. BKMR confirmed above metals and revealed a linearly in-verse joint association between 15 metals and LTL. Q-g regression further indicated each quantile increase in mixture was associated with 5.2% shorter LTL (95% CI:-8.1%,-2.3%). Furthermore, manganese counteracted against aluminum and vanadium respectively (Pint < 0.05). In addition, associations of vanadium, aluminum and metal mixture with LTL were more prominent in overweight participants. Our results are among the first to provide a new comprehensive view of metal mixture exposure on LTL attrition in the general population, including identifying the major components, metals interactions and the overall effects.