A spatiotemporal map of the aging mouse brain reveals white matter tracts as vulnerable foci
A spatiotemporal map of the aging mouse brain reveals white matter tracts as vulnerable foci
Summary Aging is the key risk factor for cognitive decline, yet the molecular changes underlying brain aging remain poorly understood. Here, we conducted spatiotemporal RNA-seq of the mouse brain, profiling 1,076 samples from 15 regions across 7 ages and 2 rejuvenation interventions. Our analysis identified a brain-wide gene signature of aging in glial cells, which exhibited spatially defined changes in magnitude. By integrating spatial and single-nucleus transcriptomics, we found that glia aging was particularly accelerated in white matter compared to cortical regions, while specialized neuronal populations showed region-specific expression changes. Rejuvenation interventions, including young plasma injection and dietary restriction, exhibited distinct effects on gene expression in specific brain regions. Furthermore, we discovered differential gene expression patterns associated with three human neurodegenerative diseases, highlighting the importance of regional aging as a potential modulator of disease. Our findings identify molecular foci of brain aging, providing a foundation to target age-related cognitive decline.
Kaur Achint、Lehallier Benoit、Lu Nannan、Zhang Hui、Huguenard John R、Partridge Linda、Atkins Micaiah、Kedir Blen、Hull Jacob、Wyss-Coray Tony、Foltz Aulden G、Hahn Oliver、P¨￠lovics R¨?bert、Moran-Losada Patricia、Keller Andreas、Gr?nke Sebastian、Guldner Ian H、Kern Fabian、Munson Christy
Department of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineAlkahest Inc.Department of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineMax Planck Institute for Biology of Ageing||Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College LondonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of Medicine||Paul F. Glenn Center for the Biology of Aging, Stanford University USA||Stanford University, The Knight Initiative for Brain ResilienceDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineClinical Bioinformatics, Saarland University||Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI)Max Planck Institute for Biology of AgeingDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of MedicineClinical Bioinformatics, Saarland University||Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI)Department of Neurology and Neurological Sciences, Stanford University School of Medicine||Wu Tsai Neurosciences Institute, Stanford University School of Medicine||Vilcek Institute of Graduate Biomedical Sciences, NYU Langone Health
神经病学、精神病学基础医学生物科学研究方法、生物科学研究技术
Kaur Achint,Lehallier Benoit,Lu Nannan,Zhang Hui,Huguenard John R,Partridge Linda,Atkins Micaiah,Kedir Blen,Hull Jacob,Wyss-Coray Tony,Foltz Aulden G,Hahn Oliver,P¨￠lovics R¨?bert,Moran-Losada Patricia,Keller Andreas,Gr?nke Sebastian,Guldner Ian H,Kern Fabian,Munson Christy.A spatiotemporal map of the aging mouse brain reveals white matter tracts as vulnerable foci[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/2022.09.18.508419.点此复制
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