Negative Correlation of RNA Epigenetic Modifications of N6-methyladenosine and 5-methylcytosine with Aging
首发时间:2016-05-27
Abstract:Aging is characterized by progressive decline in physiology and function of adult tissues. Previous studies demonstrated DNA methylation is related to aging. In addition to DNA methylation, reversible RNA modification has recently been proposed to represent another realm for biological regulation in the form of "RNA epigenetics". However, the correlation of emerging RNA epigenetic modifications in aging process is still a mystery. Here we developed an on-line trapping/capillary hydrophilic-interaction liquid chromatography/electrospray ionization-mass spectrometry method for ultra-sensitive and simultaneous quantification of RNA epigenetic modifications of N6-methyladenosine (m6A) and 5-methylcytosine (5-mC) from human blood. We analyzed the contents of m6A and 5-mC in RNA of blood from 260 healthy persons aged from 0 to 88 years old. The results showed that both m6A and 5-mC contents were significantly decreased and highly correlated with aging process. We then established RNA epigenetic modifications age models according to m6A and 5-mC contents with an mean absolute deviation of 6.7 years for m6A and 8.0 years for 5-mC. This study demonstrated RNA epigenetic modifications of m6A and 5-mC represents strong and reproducible marks of chronological age, which could be potentially applied in health assessment and prevention of diseases.
keywords: Analytical chemistry N6-methyladenosine, 5-methylcytosine, aging, hydrophilic-interaction liquid chromatography, capillary monolithic column
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RNA中N6-甲基腺嘌呤修饰和5-甲基胞嘧啶修饰与年龄的相关性研究
摘要:衰老的特征在于生理和成人组织的功能的下降。以往的研究表明DNA甲基化与老化相关。除了DNA甲基化,近期研究表明,可逆的RNA修饰是"RNA表观遗传学"的另外一个表现方式。然而,在衰老过程中,RNA表观遗传修饰与年龄的关系仍然不清楚。在这里,我们开发了一种在线富集/毛细管亲水作用色谱/电喷雾电离质谱连用的方法超灵敏的测定了人血液RNA的表观遗传修饰N6-甲基腺苷(m6A)和5-甲基胞嘧啶(5-mC)方法。我们分析了260例年龄0到88岁的健康人血液RNA中m6A和5-mC的含量。结果表明,这两种修饰核苷的含量显著降低,与衰老进程高度相关。然后,根据m6A和5-mC的含量与年龄的关系建立了RNA表观修饰的年龄模型,在建立的模型中m6A和5-mC的平均绝对偏差为6.7岁和8.0岁。这项研究表明m6A和5-mC的RNA的表观遗传修饰与实际年龄高度相关,这项发现可能在健康评估和预防疾病有潜在的应用。
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No.4691753115027814****
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