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

Atlas of the aging mouse brain reveals white matter as vulnerable foci. Hahn, O., Foltz, A., Atkins, M., Kedir, B., Moran Losada, P., Guldner, I., Munson, C., Kern, F., Pálovics, R., Lu, N., Zhang, H., Kaur, A., Hull, J., Huguenard, J., Groenke, S., Lehallier, B., Partridge, L., Keller, A., & Wyss-Coray, T. Cell, 186, 08, 2023.

Paper doi abstract bibtex

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.

@article{hahn0123,
	author = {Hahn, Oliver and Foltz, Aulden and Atkins, Micaiah and Kedir, Blen and Moran Losada, Patricia and Guldner, Ian and Munson, Christy and Kern, Fabian and Pálovics, Róbert and Lu, Nannan and Zhang, Hui and Kaur, Achint and Hull, Jacob and Huguenard, John and Groenke, Sebastian and Lehallier, Benoit and Partridge, Linda and Keller, Andreas and Wyss-Coray, Tony},
	year = {2023},
	month = {08},
	abstract = "{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.}",
	pages = {},
	title = {Atlas of the aging mouse brain reveals white matter as vulnerable foci},
	volume = {186},
	journal = {Cell},
	doi = {10.1016/j.cell.2023.07.027},
    	url = {https://doi.org/10.1016/j.cell.2023.07.027}
}

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