老年人 24 小时尿液金属浓度与 DNA 甲基化年龄变量的个体物种和累积混合物关系。
Individual species and cumulative mixture relationships of 24-hour urine metal concentrations with DNA methylation age variables in older men.
机构信息
Belfer Center for Science and International Affairs, Harvard Kennedy School of Government, Department of Environmental Health, Harvard T.H. Chan School of Public Health, and MD/PhD Program, Harvard Medical School, Boston, MA, USA.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
出版信息
Environ Res. 2020 Jul;186:109573. doi: 10.1016/j.envres.2020.109573. Epub 2020 Apr 25.
BACKGROUND
Globally, toxic metal exposures are a well-recognized risk factor for many adverse health outcomes. DNA methylation-based measures of biological aging are predictive of disease, but have poorly understood relationships with metal exposures.
OBJECTIVE
We performed a pilot study examining the relationships of 24-h urine metal concentrations with three novel DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge.
METHODS
We utilized a previously established urine panel of five common metals [arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg)] found in a subset of the elderly US Veterans Affairs Normative Aging Study cohort (N = 48). The measures of DNA methylation-based biological age were calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. Bayesian Kernel Machine Regression (BKMR) was used to determine metals most important to the aging outcomes and the relationship of the cumulative metal mixture with the outcomes. Individual relationships of important metals with the biological aging outcomes were modeled using fully-adjusted linear models controlling for chronological age, renal function, and lifestyle/environmental factors.
RESULTS
Mn was selected as important to PhenoAge. A 1 ng/mL increase in urine Mn was associated with a 9.93-year increase in PhenoAge (95%CI: 1.24, 18.61, p = 0.03). The cumulative urine metal mixture was associated with increases in PhenoAge. Compared to a model where each metal in the mixture is set to its 50th percentile value, every one-unit increase of the cumulative mixture with each metal at its 70th percentile was associated with a 2.53-year increase in PhenoAge (95%CI: 0.10, 4.96, P<0.05).
CONCLUSION
Our results add novel evidence that metals detected in urine are associated with increases in biological aging and suggest that these DNA methylation-based measures may be useful for identifying individuals at-risk for diseases related to toxic metal exposures. Further research is necessary to confirm these findings more broadly.
背景
在全球范围内，有毒金属暴露是许多不良健康后果的公认危险因素。基于 DNA 甲基化的生物老化测量可预测疾病，但与金属暴露的关系尚未得到充分理解。
目的
我们进行了一项初步研究，检查了 24 小时尿液金属浓度与三种新的基于 DNA 甲基化的生物老化测量值（DNAmAge、GrimAge 和 PhenoAge）之间的关系。
方法
我们利用了先前在老年美国退伍军人事务规范研究队列的亚组中建立的尿液五常见金属（砷[As]、镉[Cd]、铅[Pb]、锰[Mn]和汞[Hg]）面板。使用 Illumina HumanMethylation450 BeadChip 上的 CpG 位点计算基于 DNA 甲基化的生物年龄测量值。贝叶斯核机器回归（BKMR）用于确定对老化结果最重要的金属以及累积金属混合物与结果的关系。使用完全调整的线性模型，通过控制年龄、肾功能和生活方式/环境因素，对重要金属与生物老化结果的个体关系进行建模。
结果
Mn 被选为与 PhenoAge 相关的重要因素。尿液 Mn 增加 1ng/ml 与 PhenoAge 增加 9.93 岁相关（95%CI：1.24，18.61，p=0.03）。累积尿液金属混合物与 PhenoAge 增加相关。与混合物中每种金属都设置为其第 50 百分位数值的模型相比，当混合物中每种金属的累积值增加到第 70 百分位数时，PhenoAge 增加 2.53 岁（95%CI：0.10，4.96，P<0.05）。
结论
我们的结果提供了新的证据，表明尿液中检测到的金属与生物老化的增加有关，并表明这些基于 DNA 甲基化的测量值可能有助于识别与有毒金属暴露相关疾病风险的个体。需要进一步研究来更广泛地证实这些发现。
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