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The epigenetic landscape of age-related diseases: the geroscience perspective

机译:与年龄有关的疾病的表观遗传学景观:从年龄科学的角度

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摘要

In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of “geroscience”, which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases. DNA methylation undergoes a profound remodeling during aging, which includes global hypomethylation of the genome, hypermethylation at specific loci and an increase in inter-individual variation and in stochastic changes of DNA methylation values. These epigenetic modifications can be an important contributor to the development of age-related diseases, but our understanding on the complex relationship between the epigenetic signatures of aging and age-related disease is still poor. The most relevant results in this field come from the use of the so called “epigenetics clocks” in cohorts of subjects affected by age-related diseases. We report these studies in final section of this review.
机译:在这篇综述中,我们总结了有关年龄相关疾病的表观遗传学的当前知识,重点是描述了心血管疾病,肌肉骨骼功能和虚弱的DNA甲基化态势的那些研究。我们强调采用“基因组学”概念框架的重要性,该概念框架的发现始于高龄是其中几种病理的主要危险因素,并旨在确定衰老与年龄相关疾病之间的机制联系。 DNA甲基化在衰老过程中经历了深刻的重塑,包括基因组的整体甲基化不足,特定位点的甲基化过度以及个体间变异和DNA甲基化值随机变化的增加。这些表观遗传修饰可能是与年龄有关的疾病发展的重要因素,但我们对衰老的表观遗传特征与与年龄有关的疾病之间复杂关系的理解仍然很差。该领域最相关的结果来自在受年龄相关疾病影响的人群中使用所谓的“表观遗传学时钟”。我们在本评论的最后部分报告这些研究。

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