Institute of Neurology, Guangzhou University of Chinese Medicine, Guangzhou, China.
The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Endocrinol (Lausanne). 2024 May 10;15:1372518. doi: 10.3389/fendo.2024.1372518. eCollection 2024.
Aging has always been considered as a risk factor for neurodegenerative diseases, but there are individual differences and its mechanism is not yet clear. Epigenetics may unveil the relationship between aging and neurodegenerative diseases.
Our study employed a bidirectional two-sample Mendelian randomization (MR) design to assess the potential causal association between epigenetic aging and neurodegenerative diseases. We utilized publicly available summary datasets from several genome-wide association studies (GWAS). Our investigation focused on multiple measures of epigenetic age as potential exposures and outcomes, while the occurrence of neurodegenerative diseases served as potential exposures and outcomes. Sensitivity analyses confirmed the accuracy of the results.
The results show a significant decrease in risk of Parkinson's disease with GrimAge (OR = 0.8862, 95% CI 0.7914-0.9924, = 0.03638). Additionally, we identified that HannumAge was linked to an increased risk of Multiple Sclerosis (OR = 1.0707, 95% CI 1.0056-1.1401, = 0.03295). Furthermore, we also found that estimated plasminogen activator inhibitor-1(PAI-1) levels demonstrated an increased risk for Alzheimer's disease (OR = 1.0001, 95% CI 1.0000-1.0002, = 0.04425). Beyond that, we did not observe any causal associations between epigenetic age and neurodegenerative diseases risk.
The findings firstly provide evidence for causal association of epigenetic aging and neurodegenerative diseases. Exploring neurodegenerative diseases from an epigenetic perspective may contribute to diagnosis, prognosis, and treatment of neurodegenerative diseases.
衰老一直被认为是神经退行性疾病的一个风险因素，但个体之间存在差异，其机制尚不清楚。表观遗传学可能揭示衰老与神经退行性疾病之间的关系。
我们采用双向两样本孟德尔随机化（MR）设计来评估表观遗传衰老与神经退行性疾病之间潜在的因果关系。我们利用了来自多个全基因组关联研究（GWAS）的公开可用汇总数据集。我们的研究集中在多种表观遗传年龄衡量标准作为潜在暴露和结局，而神经退行性疾病的发生作为潜在暴露和结局。敏感性分析证实了结果的准确性。
结果表明，GrimAge 使帕金森病的风险显著降低（OR = 0.8862，95%CI 0.7914-0.9924， = 0.03638）。此外，我们发现 HannumAge 与多发性硬化症的风险增加相关（OR = 1.0707，95%CI 1.0056-1.1401， = 0.03295）。此外，我们还发现估计的纤溶酶原激活物抑制剂-1（PAI-1）水平与阿尔茨海默病的风险增加相关（OR = 1.0001，95%CI 1.0000-1.0002， = 0.04425）。除此之外，我们没有观察到表观遗传年龄与神经退行性疾病风险之间的任何因果关系。
这些发现首次为表观遗传衰老与神经退行性疾病之间的因果关系提供了证据。从表观遗传学角度探索神经退行性疾病可能有助于神经退行性疾病的诊断、预后和治疗。
