Determinants of accelerated metabolomic and epigenetic aging in a UK cohort.,Aging Cell

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Determinants of accelerated metabolomic and epigenetic aging in a UK cohort.
Aging Cell ( IF 8.0 ) Pub Date : 2020-05-03 , DOI: 10.1111/acel.13149
Oliver Robinson ₁ , Marc Chadeau Hyam ₁ , Ibrahim Karaman ₁ , Rui Climaco Pinto ₁ , Mika Ala-Korpela _{2,

3} , Evangelos Handakas ₁ , Giovanni Fiorito _{1,

4,

5} , He Gao ₁ , Andy Heard ₁ , Marjo-Riitta Jarvelin _{1,

6,

7} , Matthew Lewis ₈ , Raha Pazoki _{1,

7} , Silvia Polidoro _{1,

5} , Ioanna Tzoulaki ₁ , Matthias Wielscher ₁ , Paul Elliott ₁ , Paolo Vineis _{1,

5}

Affiliation

Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.

中文翻译：

英国队列加速代谢组和表观遗传衰老的决定因素。

生物衰老标志物在初级保健和公共卫生方面具有潜在的用途。我们在来自 UK Airwave 队列的大样本 ( N = 2,239) 中开发了一个基于跨多个平台的非目标代谢分析的年龄模型，包括核磁共振波谱法和尿液和血清中的液相色谱-质谱法。我们在芬兰队列中验证了模型预测因子的子集，包括对 2,144 名个体的重复测量。我们研究了加速衰老的决定因素，包括导致过早死亡的生活方式和心理风险因素。代谢组年龄模型与实际年龄密切相关（独立测试集的平均值r = 0.86）。错误发现率 (FDR) 校正后，代谢组年龄加速 (mAA) 增加与超重/肥胖、糖尿病、酗酒和抑郁症相关。 DNA 甲基化年龄加速测量与 mAA 不相关。 FDR 校正后，DNA 甲基化表型年龄加速（ N = 1,110）增加与酗酒、高血压和低收入相关。总之，代谢组学是评估生物年龄的一种有前途的方法，并且似乎与已建立的表观遗传时钟互补。

更新日期：2020-05-03

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