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基于 DNA 甲基化的生物老化加速指标与最年长人群痴呆风险的关系:洛锡安出生队列 1921 年研究。

DNA methylation-based measures of accelerated biological ageing and the risk of dementia in the oldest-old: a study of the Lothian Birth Cohort 1921.

机构信息

Alzheimer Scotland Dementia Research Centre, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.

出版信息

BMC Psychiatry. 2020 Feb 28;20(1):91. doi: 10.1186/s12888-020-2469-9.

Abstract

BACKGROUND

Previous studies have demonstrated an association between DNA methylation-based measures of accelerated ageing and age-related health outcomes and mortality. As a disease closely associated with advancing age, we hypothesized that DNA methylation-based measures of accelerated ageing might be associated with risk for dementia. This study therefore aimed to examine the association between four recognised measures of age acceleration and subsequent dementia.

METHODS

Study subjects (n = 488) were members of the Lothian Birth Cohort 1921. Dementia case ascertainment used data from death certificates, electronic hospital records, and clinical reviews. Venous blood samples were taken at baseline, at age 79 years. DNA methylation and measures of epigenetic age were calculated in accordance with Horvath's epigenetic clock tutorial, using the online calculator (https://dnamage.genetics.ucla.edu/). From these values, four measures of accelerated ageing were calculated: extrinsic epigenetic age acceleration (EEAA), intrinsic epigenetic age acceleration (IEAA), AgeAccelPheno and AgeAccelGrim. Competing risk regression models - with death as a competing risk - were performed to examine the association between each measure of accelerated ageing and incident dementia. APOE ɛ4 status, sex, age, smoking status, history of cardiovascular disease, cerebrovascular disease, hypertension, and diabetes were included as covariates.

RESULTS

None of the multivariate models revealed a positive association between increased epigenetic age acceleration and dementia risk. Across all included models, never-smoking increased risk for dementia (HR 1.69 [1.06, 2.71], p = 0.03), and having no APOE ɛ4 alleles reduced risk for dementia (HR 0.44 [0.29, 0.67], p < 0.001).

CONCLUSIONS

The present study did not demonstrate any consistent association between DNA methylation-based measures of accelerated ageing and dementia in subjects aged over 79 years. Further, larger studies - including separate analyses of dementia subtypes - are required to further investigate the potential association between DNA methylation-based measures of accelerated ageing and dementia.

摘要

背景

先前的研究表明,基于 DNA 甲基化的加速老化测量值与与年龄相关的健康结果和死亡率之间存在关联。作为一种与年龄增长密切相关的疾病,我们假设基于 DNA 甲基化的加速老化测量值可能与痴呆风险相关。因此,本研究旨在研究四种公认的加速老化测量值与随后发生痴呆的相关性。

方法

研究对象(n=488)是洛锡安出生队列 1921 的成员。痴呆病例的确定使用了死亡证明、电子病历和临床审查的数据。静脉血样于基线和 79 岁时采集。根据 Horvath 的表观遗传时钟教程,使用在线计算器(https://dnamage.genetics.ucla.edu/)计算 DNA 甲基化和表观遗传年龄测量值。根据这些值,计算出了四种加速老化的测量值:外在表观遗传年龄加速(EEAA)、内在表观遗传年龄加速(IEAA)、AgeAccelPheno 和 AgeAccelGrim。使用竞争风险回归模型(以死亡为竞争风险)来研究每种加速老化测量值与新发痴呆的相关性。APOE ε4 状态、性别、年龄、吸烟状况、心血管疾病、脑血管疾病、高血压和糖尿病被纳入为协变量。

结果

在所有多变量模型中,增加的表观遗传年龄加速与痴呆风险之间均未显示出正相关。在所有纳入的模型中,从不吸烟增加了痴呆的风险(HR 1.69[1.06, 2.71],p=0.03),没有 APOE ε4 等位基因降低了痴呆的风险(HR 0.44[0.29, 0.67],p<0.001)。

结论

本研究未在 79 岁以上的受试者中发现基于 DNA 甲基化的加速老化测量值与痴呆之间存在任何一致的关联。进一步需要更大规模的研究(包括对痴呆亚型的单独分析),以进一步研究基于 DNA 甲基化的加速老化测量值与痴呆之间的潜在关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e2/7048023/768acf5e1c31/12888_2020_2469_Fig1_HTML.jpg

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