Conole Eleanor L S, Robertson Josephine A, Smith Hannah M, Cox Simon R, Marioni Riccardo E
Department of Biochemistry, University of Oxford, Oxford, UK.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Nat Rev Neurol. 2025 Jun 18. doi: 10.1038/s41582-025-01105-7.
Ageing has profound effects on the human brain across the lifespan. Cognitive testing and brain imaging are currently used to monitor healthy and pathological brain ageing. However, peripheral markers of cognitive function, cognitive ageing and neurological disease could provide a valuable, minimally invasive approach to tracking these processes longitudinally. In this Review, we introduce the concept of DNA methylation-based biomarkers and present current evidence of their potential to address the challenge of monitoring brain ageing and stratifying the risk of neurological disease. We focus on epigenetic clocks, which can be applied across multiple tissues and organs to estimate biological ageing, as well as on blood-based epigenetic scores (EpiScores) that can directly track brain-based phenotypes, such as cognitive function, and risk factors for neurological diseases, such as lifestyle behaviours and proteomic markers of inflammation. We discuss the associations between these epigenetic biomarkers and multiple measures of cognitive health, including cognitive test data, brain MRI measures and dementia.
衰老在人的一生中对大脑有着深远影响。目前，认知测试和脑成像被用于监测健康和病理性的大脑衰老。然而，认知功能、认知衰老和神经疾病的外周标志物可为纵向追踪这些过程提供一种有价值的、微创的方法。在本综述中，我们介绍基于DNA甲基化的生物标志物的概念，并展示目前关于其有潜力应对监测大脑衰老挑战和对神经疾病风险进行分层的证据。我们重点关注表观遗传时钟，其可应用于多个组织和器官以估计生物衰老，还关注基于血液的表观遗传评分（EpiScores），其可直接追踪基于大脑的表型，如认知功能，以及神经疾病的风险因素，如生活方式行为和炎症的蛋白质组学标志物。我们讨论了这些表观遗传生物标志物与认知健康的多种测量指标之间的关联，包括认知测试数据、脑MRI测量结果和痴呆。
