单细胞分辨率下的大脑衰老与年轻化
Brain aging and rejuvenation at single-cell resolution.
作者信息
Sun Eric D, Nagvekar Rahul, Pogson Angela N, Brunet Anne
机构信息
Department of Genetics, Stanford University, Stanford, CA, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA; Biomedical Informatics Graduate Program, Stanford University, Stanford, CA, USA.
Department of Genetics, Stanford University, Stanford, CA, USA; Genetics Graduate Program, Stanford University, Stanford, CA, USA.
出版信息
Neuron. 2025 Jan 8;113(1):82-108. doi: 10.1016/j.neuron.2024.12.007.
Brain aging leads to a decline in cognitive function and a concomitant increase in the susceptibility to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A key question is how changes within individual cells of the brain give rise to age-related dysfunction. Developments in single-cell "omics" technologies, such as single-cell transcriptomics, have facilitated high-dimensional profiling of individual cells. These technologies have led to new and comprehensive characterizations of brain aging at single-cell resolution. Here, we review insights gleaned from single-cell omics studies of brain aging, starting with a cell-type-centric overview of age-associated changes and followed by a discussion of cell-cell interactions during aging. We highlight how single-cell omics studies provide an unbiased view of different rejuvenation interventions and comment on the promise of combinatorial rejuvenation approaches for the brain. Finally, we propose new directions, including models of brain aging and neural stem cells as a focal point for rejuvenation.
大脑衰老会导致认知功能下降，并同时增加患神经退行性疾病（如阿尔茨海默病和帕金森病）的易感性。一个关键问题是大脑单个细胞内的变化如何导致与年龄相关的功能障碍。单细胞“组学”技术（如单细胞转录组学）的发展促进了对单个细胞的高维分析。这些技术已在单细胞分辨率上对大脑衰老进行了新的全面表征。在这里，我们回顾从大脑衰老的单细胞组学研究中获得的见解，首先是以细胞类型为中心概述与年龄相关的变化，然后讨论衰老过程中的细胞间相互作用。我们强调单细胞组学研究如何为不同的年轻化干预提供无偏见的观点，并对大脑组合年轻化方法的前景进行评论。最后，我们提出新的方向，包括大脑衰老模型和作为年轻化焦点的神经干细胞。
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