美国斯坦福大学医学院Tony Wyss-Coray团队发现衰老小鼠大脑的图谱显示白质是脆弱的病灶。相关论文于2023年8月16日发表在《细胞》杂志上。

他们对小鼠大脑进行了时空RNA测序，分析了来自7个衰老和2个年轻干预的15个区域的1,076个样本。他们的分析确定了神经胶质细胞衰老的全脑基因特征，其表现出空间上确定的变化幅度。通过整合空间和单核转录组学，他们发现与皮质区域相比，白质中的胶质细胞衰老尤其加速，而特化神经元群体则表现出区域特异性表达变化。年轻化干预，包括年轻血浆注射和饮食限制，对特定大脑区域的基因表达有明显的影响。

此外，他们发现了与三种人类神经退行性疾病相关的差异基因表达模式，强调了区域衰老作为疾病潜在调节剂的重要性。他们的发现确定了大脑衰老的分子病灶，为靶向与年龄相关的认知能力下降提供了基础。

据介绍，衰老是认知能力下降的关键风险因素，然而大脑衰老背后的分子变化仍然知之甚少。

附：英文原文

Title: Atlas of the aging mouse brain reveals white matter as vulnerable foci

Author: Oliver Hahn, Aulden G. Foltz, Micaiah Atkins, Blen Kedir, Patricia Moran-Losada, Ian H. Guldner, Christy Munson, Fabian Kern, Róbert Pálovics, Nannan Lu, Hui Zhang, Achint Kaur, Jacob Hull, John R. Huguenard, Sebastian Grnke, Benoit Lehallier, Linda Partridge, Andreas Keller, Tony Wyss-Coray

Issue&Volume: 2023-08-16

Abstract: Aging is the key risk factor for cognitive decline, yet the molecular changes underlyingbrain aging remain poorly understood. Here, we conducted spatiotemporal RNA sequencingof the mouse brain, profiling 1,076 samples from 15 regions across 7 ages and 2 rejuvenationinterventions. Our analysis identified a brain-wide gene signature of aging in glialcells, which exhibited spatially defined changes in magnitude. By integrating spatialand single-nucleus transcriptomics, we found that glial aging was particularly acceleratedin white matter compared with cortical regions, whereas specialized neuronal populationsshowed region-specific expression changes. Rejuvenation interventions, including youngplasma injection and dietary restriction, exhibited distinct effects on gene expressionin specific brain regions. Furthermore, we discovered differential gene expressionpatterns associated with three human neurodegenerative diseases, highlighting theimportance of regional aging as a potential modulator of disease. Our findings identifymolecular foci of brain aging, providing a foundation to target age-related cognitivedecline.

DOI: 10.1016/j.cell.2023.07.027

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00805-X