MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Aging Cell. 2021 Sep;20(9):e13452. doi: 10.1111/acel.13452. Epub 2021 Aug 20.
Advanced age is the main common risk factor for cancer, cardiovascular disease and neurodegeneration. Yet, more is known about the molecular basis of any of these groups of diseases than the changes that accompany ageing itself. Progress in molecular ageing research was slow because the tools predicting whether someone aged slowly or fast (biological age) were unreliable. To understand ageing as a risk factor for disease and to develop interventions, the molecular ageing field needed a quantitative measure; a clock for biological age. Over the past decade, a number of age predictors utilising DNA methylation have been developed, referred to as epigenetic clocks. While they appear to estimate biological age, it remains unclear whether the methylation changes used to train the clocks are a reflection of other underlying cellular or molecular processes, or whether methylation itself is involved in the ageing process. The precise aspects of ageing that the epigenetic clocks capture remain hidden and seem to vary between predictors. Nonetheless, the use of epigenetic clocks has opened the door towards studying biological ageing quantitatively, and new clocks and applications, such as forensics, appear frequently. In this review, we will discuss the range of epigenetic clocks available, their strengths and weaknesses, and their applicability to various scientific queries.
高龄是癌症、心血管疾病和神经退行性疾病的主要共同危险因素。然而,人们对这些疾病群体中的任何一种的分子基础了解得更多,而对伴随衰老本身的变化了解得却很少。分子衰老研究进展缓慢,因为预测某人衰老速度(生物年龄)的工具不可靠。为了将衰老作为疾病的一个风险因素来理解,并开发干预措施,分子衰老领域需要一个定量的衡量标准;一个生物年龄的时钟。在过去的十年中,已经开发出了许多利用 DNA 甲基化的年龄预测器,被称为表观遗传钟。虽然它们似乎可以估计生物年龄,但仍不清楚用于训练时钟的甲基化变化是否反映了其他潜在的细胞或分子过程,或者甲基化本身是否参与了衰老过程。表观遗传钟所捕捉到的衰老的精确方面仍然隐藏着,而且似乎在不同的预测器之间存在差异。尽管如此,表观遗传钟的使用为定量研究生物衰老打开了大门,并且新的时钟和应用程序,如法医学,经常出现。在这篇综述中,我们将讨论现有的各种表观遗传钟,它们的优缺点,以及它们在各种科学研究中的适用性。