D'Aquila Patrizia, Montesanto Alberto, De Rango Francesco, Guarasci Francesco, Passarino Giuseppe, Bellizzi Dina
Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende 87036, Italy.
Aging (Albany NY). 2019 Feb 20;11(4):1240-1251. doi: 10.18632/aging.101832.
Maintenance of functional mitochondria is essential to prevent damage leading to aging and diseases. What is more, the research of biomarkers of aging is focusing on better predicting functional capability along the lifetime beyond chronological age. Aim of this study was to identify novel CpG sites the methylation of which might be correlated to the chronological and biological age. We performed methylation analyses of the CpG sites in candidate genes involved in mitochondrial biogenesis, mitophagy, fusion, and fission, all key quality control mechanisms to ensure maintenance of healthy mitochondria and homeostasis during aging, using DNA samples from two independent datasets composed by 381 and 468 differently-aged individuals, respectively. Twelve potential CpG predictors resulted associated with aging in the discovery dataset. Of these, two sites located within and genes were replicated in the second dataset. What is more, individuals exhibiting methylation levels of the CpG site higher than 10% were observed more prone to disability than people with lower levels.These results seem to provide the first evidence that epigenetic modifications of genes involved in mitochondrial quality control occur over time according to the aging decline, and may then represent potential biomarkers of both chronological and biological age.
维持功能性线粒体对于预防导致衰老和疾病的损伤至关重要。此外，衰老生物标志物的研究重点在于更好地预测一生中超越实际年龄的功能能力。本研究的目的是识别新的CpG位点，其甲基化可能与实际年龄和生物学年龄相关。我们使用分别由381名和468名不同年龄个体组成的两个独立数据集的DNA样本，对参与线粒体生物发生、线粒体自噬、融合和裂变的候选基因中的CpG位点进行甲基化分析，这些都是确保衰老过程中健康线粒体维持和体内平衡的关键质量控制机制。在发现数据集中，有12个潜在的CpG预测因子与衰老相关。其中，位于 和 基因内的两个位点在第二个数据集中得到了重复验证。此外，观察到CpG位点甲基化水平高于10%的个体比水平较低的个体更容易出现残疾。这些结果似乎首次证明，参与线粒体质量控制的基因的表观遗传修饰会随着衰老衰退而随时间发生变化，进而可能代表实际年龄和生物学年龄的潜在生物标志物。
