Epigenetic age acceleration was delayed in schizophrenia
Epigenetic age acceleration was delayed in schizophrenia
复制标题
精神分裂症的表观遗传年龄加速被延迟
DOI：
10.1093/schbul/sbaa164
复制
发表时间：
2020
影响因子：
6.6
通讯作者：
Cunyou Zhao
中科院分区：
文献类型：
--
作者：
Xiaohui Wu;Junping Ye;Zhongju Wang;Cunyou Zhao
精神分裂症是一种严重的神经精神疾病，具有异常的与年龄相关的神经发育（或神经退行性）轨迹。虽然已经提出了精神分裂症的加速衰老假说，但对精神分裂症引起的生理轨迹破坏的定量研究尚无定论。在这项研究中，我们采用了3种“表观遗传时钟”方法来量化大样本的全血（精神分裂症患者1069个样本对未受影响的对照组1264个样本）和脑组织（精神分裂症患者500个样本对未受影响的对照组711个样本）的表观遗传年龄。我们观察到，在未受影响的对照组和精神分裂症患者的血液和脑组织中，表观遗传年龄和实足年龄之间存在显著的正相关，通过3种方法进行了估计。此外，我们从全血样本（20-90岁）和脑额叶皮层组织（20-39岁）中观察到，表观遗传年龄加速在精神分裂症患者中显著延迟。有趣的是，表观遗传时钟调节的基因也包含精神分裂症相关基因，在精神分裂症患者中表现出差异表达和甲基化，并参与细胞活化和发育的调节。精神分裂症患者的白细胞组成失调进一步支持了这些发现。我们的研究从扭曲的“表观遗传时钟”的角度为精神分裂症的神经发育模型提供了定量证据。此外，易于获取的生物样本血液中的里程碑式变化揭示了这些表观遗传时钟基因作为精神分裂症外围生物标志物的价值。
Schizophrenia is a serious neuropsychiatric disorder with abnormal age-related neurodevelopmental (or neurodegenerative) trajectories. Although an accelerated aging hypothesis of schizophrenia has been proposed, the quantitative study of the disruption of the physiological trajectory caused by schizophrenia is inconclusive. In this study, we employed 3 “epigenetic clock” methods to quantify the epigenetic age of a large sample size of whole blood (1069 samples from patients with schizophrenia vs 1264 samples from unaffected controls) and brain tissues (500 samples from patients with schizophrenia vs 711 samples from unaffected controls). We observed significant positive correlations between epigenetic age and chronological age in both blood and brain tissues from unaffected controls and patients with schizophrenia, as estimated by 3 methods. Furthermore, we observed that epigenetic age acceleration was significantly delayed in schizophrenia from the whole blood samples (aged 20–90 years) and brain frontal cortex tissues (aged 20–39 years). Intriguingly, the genes regulated by the epigenetic clock also contained schizophrenia-associated genes, displaying differential expression and methylation in patients with schizophrenia and involving in the regulation of cell activation and development. These findings were further supported by the dysregulated leukocyte composition in patients with schizophrenia. Our study presents quantitative evidence for a neurodevelopmental model of schizophrenia from the perspective of a skewed “epigenetic clock.” Moreover, landmark changes in an easily accessible biological sample, blood, reveal the value of these epigenetic clock genes as peripheral biomarkers for schizophrenia.