Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These measures include five ‘epigenetic clocks’ which provide an index of how much an individual’s biological age differs from their chronological age at the time of measurement. The five clocks encompass methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). A sixth epigenetic measure of ageing differs from these clocks in that it acts as a speedometer providing a single time-point measurement of the pace of an individual’s biological ageing. This measure of ageing is termed DunedinPoAm. In this study, we test the association between these six epigenetic measures of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries (n ≤ 9537, Generation Scotland: Scottish Family Health Study). DNAm GrimAge predicted incidence of clinically diagnosed chronic obstructive pulmonary disease (COPD), type 2 diabetes and ischemic heart disease after 13 years of follow-up (hazard ratios = 2.22, 1.52 and 1.41, respectively). DunedinPoAm predicted the incidence of COPD and lung cancer (hazard ratios = 2.02 and 1.45, respectively). DNAm PhenoAge predicted incidence of type 2 diabetes (hazard ratio = 1.54). DNAm Telomere Length associated with the incidence of ischemic heart disease (hazard ratio = 0.80). DNAm GrimAge associated with all-cause mortality, the prevalence of COPD and spirometry measures at the study baseline. These associations were present after adjusting for possible confounding risk factors including alcohol consumption, body mass index, deprivation, education and tobacco smoking and surpassed stringent Bonferroni-corrected significance thresholds. Our data suggest that epigenetic measures of ageing may have utility in clinical settings to complement gold-standard methods for disease assessment and management.

中文翻译：

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衰老的表观遗传测量可以预测导致死亡和疾病负担的主要原因的流行和发病率。

相同实足年龄的个体表现出不同的生物老化率。已经提出了许多生物学年龄的测量方法，这些测量方法利用了 DNA 甲基化谱中与年龄相关的变化。这些措施包括五个“表观遗传时钟”，它们提供了一个指标，表明一个人的生物学年龄与其测量时的实际年龄相差多少。这五个时钟包括基于甲基化的实足年龄预测因子（HorvathAge、HannumAge）、全因死亡率（DNAm PhenoAge、DNAm GrimAge）和端粒长度（DNAm Telomere Length）。衰老的第六种表观遗传测量不同于这些时钟，因为它充当速度计，提供个体生物衰老速度的单个时间点测量。这种老化测量被称为但尼丁PoAm。在这项研究中，我们测试了这六种衰老表观遗传测量与高收入国家疾病负担和死亡率的主要原因的患病率和发病率之间的关联（n ≤ 9537，苏格兰一代：苏格兰家庭健康研究）。DNAm GrimAge 预测了 13 年随访后临床诊断为慢性阻塞性肺病 (COPD)、2 型糖尿病和缺血性心脏病的发病率（风险比分别为 2.22、1.52 和 1.41）。DunedinPoAm 预测 COPD 和肺癌的发病率（风险比分别为 2.02 和 1.45）。DNAm PhenoAge 预测 2 型糖尿病的发病率（风险比 = 1.54）。DNAm 端粒长度与缺血性心脏病的发病率相关（风险比 = 0.80）。DNAm GrimAge 与全因死亡率相关，研究基线时 COPD 的患病率和肺活量测量值。在调整了可能的混杂风险因素（包括饮酒、体重指数、剥夺、教育和吸烟）并超过了严格的 Bonferroni 校正显着性阈值后，这些关联就出现了。我们的数据表明，衰老的表观遗传测量可能在临床环境中发挥作用，以补充疾病评估和管理的金标准方法。