The impact of genetic susceptibility and the role of aging acceleration in the association of urinary zinc with lung function decline: A repeated-measures study

BACKGROUND: Zinc pollution is alarming, demanding urgent attention to its adverse effects. METHODS: The prospective study was conducted among 10057 general Chinese observations from the Wuhan-Zhuhai cohort. Genetic susceptibility was assessed by calculating the lung function-related polygenic risk score (PRS). Aging acceleration of Klemera-Doubal age (KDM_AA) and phenotypic age (PHE_AA) were constructed from clinical parameters. The associations between urinary zinc and lung function were assessed using group-based trajectory models and linear mixed models (LMMs). The relationships of urinary zinc with KDM_AA and PHE_AA were evaluated using LMMs, and the mediating role of aging acceleration was assessed via longitudinal mediation analyses. RESULTS: Urinary zinc was negatively associated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁), especially in the third PRS quantile group. Each 1-unit increase in ln-transformed value of urinary zinc was associated with the annual change rate in FVC and FEV₁ of -10.624 (95 % confidence interval -17.617, -3.550) mL/year and -6.826 (-12.113, -1.469) mL/year, respectively. Positive longitudinal associations were observed between urinary zinc and aging acceleration, with the annual change rate of 0.128 (0.038, 0.219) years/year for KDM_AA and 0.077 (0.036, 0.118) years/year for PHE_AA. Moreover, aging acceleration partially mediated the associations of urinary zinc with FVC and FEV₁, and the mediated proportion ranged from 11.38 % to 18.60 %. CONCLUSIONS: Zinc exposure was associated with lung function decline especially among individuals genetically vulnerable. Biological aging acceleration caused by zinc exposure may be the potential mechanism.