Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype

Matsudaira, Tatsuyuki; Nakano, Sosuke; Konishi, Yusuke; Kawamoto, Shimpei; Uemura, Ken; Kondo, Tamae; Sakurai, Koki; Ozawa, Takaaki; Hikida, Takatoshi; Komine, Okiru; Yamanaka, Koji; Fujita, Yuki; Yamashita, Toshihide; Matsumoto, Tomonori; Hara, Eiji

doi:https://doi.org/10.1038/s42003-023-05027-2

Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype

Matsudaira, Tatsuyuki; Nakano, Sosuke; Konishi, Yusuke et al.

Communications Biology, 2023, 6(1), 665

Number of Access:1,930（2025-08-15 01:09 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/92727

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Title	Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype
Creator	NRID 1000020812267 1000020812267 researchmap permalink matsudaira_tatsuyuki matsudaira_tatsuyuki Scopus Author ID 57216526595 57216526595 CreatorName Matsudaira, Tatsuyuki
	CreatorName Nakano, Sosuke
	CreatorName Konishi, Yusuke
	NRID 1000040612081 1000040612081 researchmap permalink kawamoto_shimpei kawamoto_shimpei Scopus Author ID 26648536400 26648536400 CreatorName Kawamoto, Shimpei
	CreatorName Uemura, Ken
	CreatorName Kondo, Tamae
	researchmap permalink kokisakurai kokisakurai CreatorName Sakurai, Koki
	NRID 1000090625352 1000090625352 ORCID 0000-0003-3633-7062 0000-0003-3633-7062 researchmap permalink takaaki_ozawa takaaki_ozawa Scopus Author ID 56312563400 56312563400 CreatorName Ozawa, Takaaki
	NRID 1000070421378 1000070421378 ORCID 0000-0002-8653-311X 0000-0002-8653-311X researchmap permalink hikida hikida Scopus Author ID 7006504625 7006504625 CreatorName Hikida, Takatoshi
	NRID 1000000456211 1000000456211 CreatorName Komine, Okiru
	NRID 1000080446533 1000080446533 CreatorName Yamanaka, Koji
	CreatorName Fujita, Yuki
	NRID 1000010301269 1000010301269 ORCID 0000-0003-4559-7018 0000-0003-4559-7018 researchmap permalink ToshihideYamashita ToshihideYamashita Scopus Author ID 35479670200 35479670200 CreatorName Yamashita, Toshihide
	NRID 1000040886610 1000040886610 ORCID 0000-0003-4483-2178 0000-0003-4483-2178 researchmap permalink tomo_matsumoto tomo_matsumoto Scopus Author ID 55628587431 55628587431 CreatorName Matsumoto, Tomonori
	NRID 1000080263268 1000080263268 ORCID 0000-0001-7821-3960 0000-0001-7821-3960 researchmap permalink read0108962 read0108962 Scopus Author ID 7004944434 7004944434 CreatorName Hara, Eiji
Description	Matsudaira T., Nakano S., Konishi Y., et al. Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype. Communications Biology 6, 665 (2023); https://doi.org/10.1038/s42003-023-05027-2.
Abstract	Cellular senescence, a state of irreversible cell-cycle arrest caused by a variety of cellular stresses, is critically involved in age-related tissue dysfunction in various organs. However, the features of cells in the central nervous system that undergo senescence and their role in neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis and various mouse models, we show that microglia, particularly in the white matter, undergo cellular senescence in the brain and spinal cord during ageing and in disease models involving demyelination. Microglial senescence is predominantly detected in disease-associated microglia, which appear in ageing and neurodegenerative diseases. We also find that commensal bacteria promote the accumulation of senescent microglia and disease-associated microglia during ageing. Furthermore, knockout of p16 INK4a, a key senescence inducer, ameliorates the neuroinflammatory phenotype in damaged spinal cords in mice. These results advance our understanding of the role of cellular senescence in the central nervous system and open up possibilities for the treatment of age-related neural disorders.
Publisher	Nature Research
Source Title	Communications Biology
Volume (Issue)	6(1)
Page	665
Date of Issued	2023-12-01
Language	English
Handle URL	https://hdl.handle.net/11094/92727
eISSN	23993642
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s42003-023-05027-2
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Communications Biology. 2023, 6(1), p. 665
DC.title	Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype
DC.creator	Matsudaira, Tatsuyuki
	Nakano, Sosuke
	Konishi, Yusuke
	Kawamoto, Shimpei
	Uemura, Ken
	Kondo, Tamae
	Sakurai, Koki
	Ozawa, Takaaki
	Hikida, Takatoshi
	Komine, Okiru
	Yamanaka, Koji
	Fujita, Yuki
	Yamashita, Toshihide
	Matsumoto, Tomonori
	Hara, Eiji
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-12-01
DC.identifier	https://doi.org/10.1038/s42003-023-05027-2
DC.description	Matsudaira T., Nakano S., Konishi Y., et al. Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype. Communications Biology 6, 665 (2023); https://doi.org/10.1038/s42003-023-05027-2.
DCTERMS.abstract	Cellular senescence, a state of irreversible cell-cycle arrest caused by a variety of cellular stresses, is critically involved in age-related tissue dysfunction in various organs. However, the features of cells in the central nervous system that undergo senescence and their role in neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis and various mouse models, we show that microglia, particularly in the white matter, undergo cellular senescence in the brain and spinal cord during ageing and in disease models involving demyelination. Microglial senescence is predominantly detected in disease-associated microglia, which appear in ageing and neurodegenerative diseases. We also find that commensal bacteria promote the accumulation of senescent microglia and disease-associated microglia during ageing. Furthermore, knockout of p16 INK4a, a key senescence inducer, ameliorates the neuroinflammatory phenotype in damaged spinal cords in mice. These results advance our understanding of the role of cellular senescence in the central nervous system and open up possibilities for the treatment of age-related neural disorders.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	92727
citation_title	Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype
citation_author	Matsudaira, Tatsuyuki
	Nakano, Sosuke
	Konishi, Yusuke
	Kawamoto, Shimpei
	Uemura, Ken
	Kondo, Tamae
	Sakurai, Koki
	Ozawa, Takaaki
	Hikida, Takatoshi
	Komine, Okiru
	Yamanaka, Koji
	Fujita, Yuki
	Yamashita, Toshihide
	Matsumoto, Tomonori
	Hara, Eiji
citation_publisher	Nature Research
citation_language	English
citation_date	2023-12-01
citation_journal_title	Communications Biology
citation_volume	6
citation_issue	1
citation_firstpage	665
citation_doi	https://doi.org/10.1038/s42003-023-05027-2
citation_public_url	https://hdl.handle.net/11094/92727

Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype

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