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Updated: Oct 18, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Identification of distinct and age-dependent p16High microglia subtypes
Nynke Talma1,2, Emma Gerrits1, Boshi Wang2
1Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
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.
Insights
Aging brains accumulate p16-high cells, primarily microglia, linked to neurodegeneration. Researchers identified two distinct microglia populations, one age-associated and one present in youth, impacting brain health.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Cellular senescence, marked by p16 expression, is implicated in aging and age-related diseases like neurodegeneration.
- p16-high cells accumulate in aging tissues, contributing to pathologies.
Purpose of the Study:
- To investigate the role and characteristics of p16-high cells in the aging central nervous system (CNS).
- To identify the specific cell types and subpopulations expressing p16 in the brain.
Main Methods:
- Bulk and single-cell RNA sequencing (RNAseq) of mouse brain cells.
- Analysis of p16-high cell populations in aged and young mice, as well as aged human brains.
Main Results:
- p16-high cells significantly increase in the aging mouse CNS.
- Single-cell RNAseq identified p16-high cells as primarily microglia.
- Two distinct p16-high microglia subpopulations were found: one age-associated and one present in young animals.
- These microglia populations differed from known disease-associated microglia and showed partial senescence signatures.
Conclusions:
- The study reveals two distinct p16-expressing microglia populations in the brain.
- One population accumulates with age, while the other is present in youth.
- These microglia subpopulations may influence brain homeostasis, function, and disease pathogenesis.
