Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed 'DNAm GrimAge' has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (β = -0.11), lower age 73 general cognitive ability (β = -0.18), decreased brain volume (β = -0.25) and increased brain white matter hyperintensities (β = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.

中文翻译：

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死亡的表观遗传预测因子捕获大脑健康的多模式测量。

相同实际年龄的个体表现出不同的生物衰老率。因此，已经提出了许多方法来确定生物年龄，并主要利用 DNA 甲基化 (DNAm) 水平的变异。一种名为“DNAm GrimAge”的新型表观遗传时钟在预测死亡风险以及许多与年龄相关的发病率方面优于其前身。然而，DNAm GrimAge 与认知或神经影像学表型之间的关联仍然未知。我们在 1936 年洛锡安出生队列（n = 709，平均年龄 73 岁）中探索这些关联。更高的 DNAm GrimAge 与第八个十年的全因死亡率密切相关（GrimAge 每标准差增加的风险比：1.81，P < 2.0 × 10-16）。较高的 DNAm GrimAge 与较低的 11 岁智商相关 (β = -0.11)，较低的 73 岁一般认知能力 (β = -0.18)、脑容量减少 (β = -0.25) 和脑白质高信号增加 (β = 0.17)。有初步证据表明 DNAm GrimAge 与 70 岁至 79 岁的认知能力下降之间存在纵向关联。测​​试的 137 种健康和大脑相关表型中有 69 种与 GrimAge 显着相关。调整所有儿童智力模型后，少数关联（12/69 个关联；其中 6 个是认知特征）减弱为不显着，但与一般认知能力的关联没有减弱（衰减 33.9%）。较高的 DNAm GrimAge 与老年人较低的认知能力和脑血管病变有关，与早年认知能力无关。