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表观遗传衰老:生物年龄预测与衰老机制理论的启示。

Epigenetic aging: Biological age prediction and informing a mechanistic theory of aging.

机构信息

Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, California, USA.

出版信息

J Intern Med. 2022 Nov;292(5):733-744. doi: 10.1111/joim.13533. Epub 2022 Jun 20.

Abstract

Numerous studies have shown that epigenetic age-an individual's degree of aging based on patterns of DNA methylation-can be computed and is associated with an array of factors including diet, lifestyle, genetics, and disease. One can expect that still further associations will emerge with additional aging research, but to what end? Prediction of age was an important first step, but-in our view-the focus must shift from chasing increasingly accurate age computations to understanding the links between the epigenome and the mechanisms and physiological changes of aging. Here, we outline emerging areas of epigenetic aging research that prioritize biological understanding and clinical application. First, we survey recent progress in epigenetic clocks, which are beginning to predict not only chronological age but aging outcomes such as all-cause mortality and onset of disease, or which integrate aging signals across multiple biological processes. Second, we discuss research that exemplifies how investigation of the epigenome is building a mechanistic theory of aging and informing clinical practice. Such examples include identifying methylation sites and the genes most strongly predictive of aging-a subset of which have shown strong potential as biomarkers of neurodegenerative disease and cancer; relating epigenetic clock predictions to hallmarks of aging; and using longitudinal studies of DNA methylation to characterize human disease, resulting in the discovery of epigenetic indications of type 1 diabetes and the propensity for psychotic experiences.

摘要

大量研究表明,基于 DNA 甲基化模式的表观遗传年龄(个体的衰老程度)可以计算出来,并与饮食、生活方式、遗传和疾病等一系列因素有关。人们可以预期,随着更多的衰老研究的出现,还会出现更多的关联,但目的是什么呢?预测年龄是一个重要的第一步,但在我们看来,重点必须从追求越来越精确的年龄计算转移到理解表观基因组与衰老的机制和生理变化之间的联系。在这里,我们概述了新兴的表观遗传衰老研究领域,这些领域优先重视生物学理解和临床应用。首先,我们调查了表观遗传时钟的最新进展,这些时钟开始不仅预测年龄,还预测衰老的结果,如全因死亡率和疾病的发生,或者整合多个生物学过程中的衰老信号。其次,我们讨论了一些研究,这些研究例证了对表观基因组的研究如何构建衰老的机制理论,并为临床实践提供信息。例如,确定甲基化位点和对衰老最具预测性的基因,其中一部分作为神经退行性疾病和癌症的生物标志物具有很大的潜力;将表观遗传时钟的预测与衰老的标志联系起来;并利用 DNA 甲基化的纵向研究来描述人类疾病,从而发现 1 型糖尿病的表观遗传迹象和精神病经历的倾向。

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