PDF(Pubmed)
Abstract：
Ageing is a continuous process that can cause neurodevelopmental changes in the body. Several studies have examined its effects, but few have focused on how time affects biological processes in the early stages of brain development. As studying the changes that occur in the early stages of life is important to prevent age-related neurological and psychiatric disorders, we aim to focus on these changes. The transcriptomic markers of ageing that are common to the analysed brain regions of C57Bl/6J mice were identified after conducting two-way ANOVA tests and effect size analysis on the time courses of gene expression profiles in various mouse brain regions. A total of 16,374 genes (59.9%) significantly changed their expression level, among which 7600 (27.8%) demonstrated tissue-dependent differences only, and 1823 (6.7%) displayed time-dependent and tissue-independent responses. Focusing on genes with at least a large effect size gives the list of potential biomarkers 12,332 (45.1%) and 1670 (6.1%) genes, respectively. There were 305 genes that exhibited similar significant time response trends (independently of the brain region). Samples from an 11-day-old mouse embryo validated the identified early-stage brain ageing markers. The overall functional analysis revealed tRNA and rRNA processing in the mitochondrion and contact activation system (CAS), as well as the kallikrein/kinin system (KKS), together with clotting cascade and defective factor F9 activation being affected by ageing. Most ageing-related pathways were significantly enriched, especially those that are strongly connected to development processes and neurodegenerative diseases.
摘要：
衰老是一个连续的过程，可以引起体内神经发育的变化。一些研究已经检查了它的影响，但是很少有人关注时间如何影响大脑发育早期阶段的生物过程。由于研究生命早期发生的变化对于预防与年龄有关的神经和精神疾病很重要，我们的目标是关注这些变化。在对各种小鼠脑区域中的基因表达谱的时间进程进行双向ANOVA测试和效应大小分析之后,鉴定了C57Bl/6J小鼠的分析脑区域所共有的衰老的转录组标志物。共有16374个基因(59.9%)表达水平发生显著变化,其中7600（27.8%）仅表现出组织依赖性差异，和1823（6.7％）显示时间依赖性和组织非依赖性反应。专注于具有至少一个大效应大小的基因给出了潜在的生物标志物列表12,332（45.1％）和1670（6.1％）基因，分别。有305个基因表现出相似的显着时间响应趋势（与大脑区域无关）。来自11天大的小鼠胚胎的样品验证了鉴定的早期脑老化标记。整体功能分析显示线粒体和接触激活系统（CAS）中的tRNA和rRNA加工，以及激肽释放酶/激肽系统(KKS)，与凝血级联反应和缺陷因子F9激活一起受到老化的影响。大多数与衰老相关的途径都显著丰富，尤其是那些与发育过程和神经退行性疾病密切相关的疾病。
