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. Hahn, O., Foltz, A. G, Atkins, M., Kedir, B., Moran-Losada, P., Guldner, I. H, Munson, C., Kern, F., Pálovics, R., Lu, N., Zhang, H., Kaur, A., Hull, J., Huguenard, J. R, Grönke, S., Lehallier, B., Partridge, L., Keller, A., & Wyss-Coray, T. bioRxiv, Cold Spring Harbor Laboratory, 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-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.Competing Interest StatementThe authors have declared no competing interest.

@article {Hahn2022.09.18.508419,
	author = {Oliver Hahn and Aulden G Foltz and Micaiah Atkins and Blen Kedir and Patricia Moran-Losada and Ian H Guldner and Christy Munson and Fabian Kern and R{\'o}bert P{\'a}lovics and Nannan Lu and Hui Zhang and Achint Kaur and Jacob Hull and John R Huguenard and Sebastian Gr{\"o}nke and Benoit Lehallier and Linda Partridge and Andreas Keller and Tony Wyss-Coray},
	title = {A spatiotemporal map of the aging mouse brain reveals white matter tracts as vulnerable foci},
	elocation-id = {2022.09.18.508419},
	year = {2023},
	doi = {10.1101/2022.09.18.508419},
	publisher = {Cold Spring Harbor Laboratory},
	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-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.Competing Interest StatementThe authors have declared no competing interest.},
	URL = {https://www.biorxiv.org/content/early/2023/04/17/2022.09.18.508419},
	eprint = {https://www.biorxiv.org/content/early/2023/04/17/2022.09.18.508419.full.pdf},
	journal = {bioRxiv}
}

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