Identification of distinct and age‐dependent p16High microglia subtypes
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Abstract Cells expressing high levels of the cyclin‐dependent kinase (CDK)4/6 inhibitor p16 (p16High) accumulate in aging tissues and promote multiple age‐related pathologies, including neurodegeneration. Here, we show that the number of p16High cells is significantly increased in the central nervous system (CNS) of 2‐year‐old mice. Bulk RNAseq indicated that genes expressed by p16High cells were associated with inflammation and phagocytosis. Single‐cell RNAseq of brain cells indicated p16High cells were primarily microglia, and their accumulation was confirmed in brains of aged humans. Interestingly, we identified two distinct subpopulations of p16High microglia in the mouse brain, with one being age‐associated and one present in young animals. Both p16High clusters significantly differed from previously described disease‐associated microglia and expressed only a partial senescence signature. Taken together, our study provides evidence for the existence of two p16‐expressing microglia populations, one accumulating with age and another already present in youth that could positively and negatively contribute to brain homeostasis, function, and disease.
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Microglia with high p16 promoter activity exhibit signatures associated with cytokine production and T cell infiltration.
“Moreover, microglia with high p16 promoter activity exhibited signatures associated with cytokine production and T cell infiltration37.”
From Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype (2023) · cites this paper as [37]
scRNA-seq analysis of old mouse brains revealed that microglia are the primary cells expressing a reporter driven by the p16 promoter.
“Moreover, scRNA-seq analysis of old mouse brains revealed that microglia are the primary cells expressing a reporter driven by the p16 promoter37.”
From Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype (2023) · cites this paper as [37]
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- Authors
- Talma, N., Gerrits, E., Wang, B., Eggen, B. J. L., & Demaria, M.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- Eggen, Bart J.L.
- Demaria, Marco
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2021-10
- Volume
- 20
- Issue
- 10
- Pages
- e13450-e13450
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC8520715
- OpenAlex
- W3204566092
- Cited by
- 46
- References
- 68
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 7 · 2022: 3 · 2021: 1 · 2012: 1
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Universitair Medisch Centrum Groningen
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- p16, microglia, cellular senescence, aging, microglial subpopulations, neuroinflammation, phagocytosis, disease-associated microglia, brain homeostasis, single-cell transcriptomics, bulk RNA-seq
- MeSH terms
- Aging, Animals, Disease Models, Animal, Humans, Cellular Senescence, Microglia, Cyclin-Dependent Kinase Inhibitor p16, Mice
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