Abstract：
Aging is related to a progressive decline in physiological functions and is affected by environmental factors. Metal exposures are linked with many health effects, but have poorly understood associations with aging. In this study, a total of 33,916 participants from the Dongfeng-Tongji cohort were included to establish biological age (BA) predictors by using recent advanced algorithms, Klemera and Doubal method (KDM) and Mahalanobis distance. Two biological aging indexes (BAIs), recorded as KDM-accel [the residual from regressing KDM-BA on chronological age] and physiological dysregulation (PD), were separately defined and tested on their associations with mortality by using Cox proportional hazard models. Among 3320 subjects with laboratory determinations of 23 metals in plasma, the individual and overall associations between these metals and BAIs were evaluated by using multiple-linear regression and weighted quantile sum (WQS) models. Both BAIs were prospectively associated with all-cause mortality among the whole participants [KDM-accel: HR(95%CI) = 1.23(1.18, 1.29); PD: HR(95%CI) = 1.37(1.31, 1.42)]. Each 1-unit increment in ln-transformed strontium and molybdenum were cross-sectionally associated with a separate 0.71- and 0.34-year increase in KDM-accel, and each 1 % increment in copper, rubidium, strontium, cobalt was cross-sectionally associated with a separate 0.10 %, 0.10 %, 0.09 %, 0.02 % increase in PD (all FDR < 0.05). The WQS models observed mixture effects of multi-metals on aging, with a 0.20-year increase in KDM-accel and a 0.04 % increase in PD for each quartile increase in ln-transformed concentrations of all metals [KDM-accel: β(95%CI) = 0.20(0.08, 0.32); PD: β(95%CI) = 0.04(0.02, 0.06)]. Our findings revealed that plasma strontium, molybdenum, copper, rubidium and cobalt were associated with accelerated aging. Multi-metals exposure showed mixture effects on the aging process, which highlights potential preventative interventions.
摘要：
衰老与生理功能的逐渐下降有关，并受环境因素的影响。金属暴露与许多健康影响有关，但对衰老的关系知之甚少。在这项研究中,来自东风-同济队列的33,916名参与者被纳入使用最近的先进算法建立生物年龄（BA）预测因子，Klemera和Doubal方法(KDM)和马氏距离。两个生物老化指标（BAI），记录为KDM-accel[回归KDM-BA对实际年龄的残差]和生理失调（PD），通过使用Cox比例风险模型分别定义和检验它们与死亡率的关联。在3320名受试者中进行了血浆中23种金属的实验室测定，使用多元线性回归和加权分位数和(WQS)模型评估了这些金属与BAI之间的个体和总体关联.两种BAI均与所有参与者的全因死亡率相关[KDM-acel:HR(95CI)=1.23(1.18,1.29);PD:HR(95CI)=1.37(1.31,1.42)]。ln转化的锶和钼的每1个单位增量在横截面上与KDM-acel的0.71和0.34年单独增加相关，铜每增加1%，铷,锶,钴在横截面上与单独的0.10%相关联，0.10%,0.09%,PD增加0.02%(所有FDR<0.05)。WQS模型观察到多种金属对老化的混合效应，所有金属的ln-转换浓度每增加四分位数，KDM-acel增加0.20年，PD增加0.04%[KDM-acel：β（95CI）=0.20（0.08，0.32）；PD：β（95CI）=0.04（0.02，0.06）]。我们的发现揭示了等离子体锶，钼,铜，铷和钴与加速老化有关。多金属暴露对老化过程表现出混合效应，这突出了潜在的预防性干预措施。
