异位切换驱动人类大脑的衰老过程.
Beril Erdogdu1,2, Hyun Joo Ji1,3, Zoe C Rudnick1,2
1Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA.
bioRxiv : the preprint server for biology
|July 14, 2025
概括
大脑发育涉及显著的基因表达变化,称为异位切换,特别是在背侧前额皮质 (DLPFC). 这个过程使用RNA测序数据准确地预测从婴儿期到老年时的脑年龄.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- 脊侧前额皮层 (DLPFC) 对于学习和记忆等认知功能至关重要.
- 在DLPFC结构和功能的个体变异性受遗传和环境因素的影响.
- 基因表达的变化,包括替代拼接,在大脑发育过程中至关重要,但尚未完全理解.
研究的目的:
- 为了研究在人类大脑发育过程中基因同型偏好的变化.
- 在DLPFC中识别和描述一种称为"isoswitching"的现象.
- 评估异位切换在预测大脑年龄方面的潜力.
主要方法:
- 来自人类产前和产后DLPFC样本的RNA测序数据的分析.
- 鉴定表现出异型偏好显著转变的基因.
- 基于异位切换模式的预测模型的开发.
主要成果:
- 许多基因在出生前后的异形偏好中显示出戏剧性的转变.
- 成千上万的基因在一生中经历着渐进的,暂时调节的异形变化 ("异形切换").
- 异位切换模式准确地预测人类大脑的年龄,从产前阶段到80多岁.
- 在 rhesus macaque 大脑中也观察到同位素切换.
结论:
- 异位切换是驱动大脑发育和衰老的基本机制.
- 这项研究首次展示了仅使用RNA测序数据来预测大脑年龄.
- 异位切换提供了一种新的分子时钟,用于跟踪物种间的大脑成熟和衰老.
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