"GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder.
"GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder.
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“恶心”是一种死亡率的表观遗传预测指标，在重度抑郁症中加速了。
DOI：
10.1038/s41398-021-01302-0
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发表时间：
2021-04-06
影响因子：
6.8
通讯作者：
Wolkowitz OM
中科院分区：
文献类型：
--
作者：
Protsenko E;Yang R;Nier B;Reus V;Hammamieh R;Rampersaud R;Wu GWY;Hough CM;Epel E;Prather AA;Jett M;Gautam A;Mellon SH;Wolkowitz OM
重度抑郁症（MDD）与过早死亡有关，并且是一系列疾病的独立风险因素，特别是与衰老有关的疾病，如心血管疾病，糖尿病和阿尔茨海默病。然而，MDD中躯体疾病发生率增加的病理生理学机制尚不清楚。有人提出MDD代表细胞加速老化的状态，近年来已经开发了几种细胞老化的测量方法。在这些指标中，基于可预测的与年龄相关的DNA甲基化（DNAm）模式（所谓的“表观遗传时钟”）的生物学年龄估计值显示出其捕获精神疾病加速老化的能力的特别前景。最近开发的被称为“GrimAge”的DNAm指标是独一无二的，因为它是在死亡时间数据上训练的，并且在预测发病率和死亡率方面优于其前辈。然而，GrimAge尚未在MDD中进行研究。在这里，我们测量了49个身体健康的未服药的MDD患者和60个年龄匹配的健康对照者的GrimAge。我们发现，与健康对照组相比，患有MDD的个体表现出相对于其实际年龄的显著更大的GrimAge（“GrimAge”）（p = 0.001），其中位值为2年的过度细胞老化。在控制性别、当前吸烟状况和体重指数后，这种差异仍然显著（p = 0.015）。这些发现与先前关于MDD中细胞加速老化的建议一致，但这是第一次用预测过早死亡的表观遗传指标来证明这一点。
Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer’s disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Among such metrics, estimators of biological age based on predictable age-related patterns of DNA methylation (DNAm), so-called ‘epigenetic clocks’, have shown particular promise for their ability to capture accelerated aging in psychiatric disease. The recently developed DNAm metric known as ‘GrimAge’ is unique in that it was trained on time-to-death data and has outperformed its predecessors in predicting both morbidity and mortality. Yet, GrimAge has not been investigated in MDD. Here we measured GrimAge in 49 somatically healthy unmedicated individuals with MDD and 60 age-matched healthy controls. We found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age (‘AgeAccelGrim’) compared to healthy controls (p = 0.001), with a median of 2 years of excess cellular aging. This difference remained significant after controlling for sex, current smoking status, and body-mass index (p = 0.015). These findings are consistent with prior suggestions of accelerated cellular aging in MDD, but are the first to demonstrate this with an epigenetic metric predictive of premature mortality.
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DOI：
10.1176/appi.ajp.2018.17060595
发表时间：
2018-08-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Han LKM;Aghajani M;Clark SL;Chan RF;Hattab MW;Shabalin AA;Zhao M;Kumar G;Xie LY;Jansen R;Milaneschi Y;Dean B;Aberg KA;van den Oord EJCG;Penninx BWJH
通讯作者：
Penninx BWJH
影响因子：
5.7
作者：
Nevalainen T;Kananen L;Marttila S;Jylhävä J;Mononen N;Kähönen M;Raitakari OT;Hervonen A;Jylhä M;Lehtimäki T;Hurme M
通讯作者：
Hurme M
影响因子：
4.8
作者：
Bravo-Ferrer, Isabel;Cuartero, Maria I.;Moro, Maria A.
通讯作者：
Moro, Maria A.
影响因子：
5.7
作者：
Hillary, Robert F.;Stevenson, Anna J.;Marioni, Riccardo E.
通讯作者：
Marioni, Riccardo E.
影响因子：
--
作者：
Schulz, R;Beach, SR;Kop, WJ
通讯作者：
Kop, WJ