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Identification of distinct and age-dependent p16High microglia subtypes
- Source :
- Aging Cell, Aging Cell, 20(10):e13450. Wiley
- Publication Year :
- 2021
-
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.<br />P16+ microglia increases in aging brains of mice and humans. P16+ cells are found in 597 different microglia populations, including two previously unknown clusters.
- Subjects :
- Senescence
Aging
senescence
Central nervous system
Inflammation
p16
neuroscience
Mice
Cyclin-dependent kinase
medicine
cellular senescence
Animals
Humans
Cyclin-Dependent Kinase Inhibitor p16
Original Paper
biology
Microglia
Kinase
Neurodegeneration
Cell Biology
medicine.disease
Original Papers
Cell biology
Disease Models, Animal
medicine.anatomical_structure
biology.protein
medicine.symptom
Homeostasis
Subjects
Details
- Language :
- English
- ISSN :
- 14749718
- Volume :
- 20
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Aging Cell
- Accession number :
- edsair.doi.dedup.....497ec8413bfed8a727b02c1a2018e325