Department of Sociology, University of Georgia, Athens, GA 30602, USA.
Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269, USA.
Genes (Basel). 2020 Mar 14;11(3):311. doi: 10.3390/genes11030311.
Smoking is one of the leading preventable causes of morbidity and mortality worldwide, prompting interest in its association with DNA methylation-based measures of biological aging. Considerable progress has been made in developing DNA methylation-based measures that correspond to self-reported smoking status. In addition, assessment of DNA methylation-based aging has been expanded to better capture individual differences in risk for morbidity and mortality. Untested to date, however, is whether smoking is similarly related to older and newer indices of DNA methylation-based aging, and whether DNA methylation-based indices of smoking can be used in lieu of self-reported smoking to examine effects on DNA methylation-based aging measures. In the current investigation we examine mediation of the impact of self-reported cigarette consumption on accelerated, intrinsic DNA methylation-based aging using indices designed to predict chronological aging, phenotypic aging, and mortality risk, as well as a newly developed DNA methylation-based measure of telomere length. Using a sample of 500 African American middle aged smokers and non-smokers, we found that a) self-reported cigarette consumption was associated with accelerated intrinsic DNA methylation-based aging on some but not all DNA methylation-based aging indices, b) for those aging outcomes associated with self-reported cigarette consumption, DNA methylation-based indicators of smoking typically accounted for greater variance than did self-reported cigarette consumption, and c) self-reported cigarette consumption effects on DNA methylation-based aging indices typically were fully mediated by DNA methylation-based indicators of smoking (e.g., PACKYRS from GrimAge; or cg05575921 CpG site). Results suggest that when DNA methylation-based indices of smoking are substituted for self-reported assessments of smoking, they will typically fully reflect the varied impact of cigarette smoking on intrinsic, accelerated DNA methylation-based aging.
吸烟是全球导致发病和死亡的主要可预防原因之一，这促使人们对其与基于 DNA 甲基化的生物老化测量指标的关联产生了兴趣。在开发与自我报告的吸烟状况相对应的基于 DNA 甲基化的测量指标方面已经取得了相当大的进展。此外，基于 DNA 甲基化的衰老评估已扩展到更好地捕捉发病率和死亡率的个体差异。然而，迄今为止尚未测试的是吸烟是否与基于 DNA 甲基化的衰老的较旧和较新指标具有相似的相关性，以及基于 DNA 甲基化的吸烟指标是否可以替代自我报告的吸烟来检查对基于 DNA 甲基化的衰老测量指标的影响。在当前的研究中，我们使用旨在预测年龄、表型衰老和死亡风险的指数，以及新开发的基于 DNA 甲基化的端粒长度测量指标，来检验自我报告的吸烟量对加速、内在基于 DNA 甲基化的衰老的影响的中介作用。使用 500 名非裔美国中年吸烟者和非吸烟者的样本，我们发现：a）自我报告的吸烟量与一些而非所有基于 DNA 甲基化的衰老指标的加速内在基于 DNA 甲基化的衰老有关；b）对于与自我报告的吸烟量相关的衰老结果，基于 DNA 甲基化的吸烟指标通常比自我报告的吸烟量解释更大的方差；c）自我报告的吸烟量对基于 DNA 甲基化的衰老指标的影响通常完全由基于 DNA 甲基化的吸烟指标介导（例如，来自 GrimAge 的 PACKYRS；或 cg05575921 CpG 位点）。结果表明，当基于 DNA 甲基化的吸烟指标替代自我报告的吸烟评估时，它们通常会完全反映吸烟对内在、加速的基于 DNA 甲基化的衰老的各种影响。
