Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell, 2023-09, Vol.186 (19), p.4117-4133.e22

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Aging is the key risk factor for cognitive decline, yet the molecular changes underlying brain aging remain poorly understood. Here, we conducted spatiotemporal RNA sequencing 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 glial aging was particularly accelerated in white matter compared with cortical regions, whereas 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. [Display omitted] •Brain-wide gene signature of aging in glial cells with spatially defined changes•Glial cell aging is accelerated in white matter•Rejuvenation interventions have region-specific effects on gene expression•Genes implicated in neurodegenerative diseases show regional aging patterns A spatiotemporal transcriptome map of the aging mouse brain identifies region-specific acceleration of glial aging, particularly in white matter, distinctive regional responses to rejuvenation interventions, and regional age-associated expression patterns of genes tied to human neurodegenerative diseases.