Phenotypic and functional differences between senescent and aged murine microglia
Abstract
Microglia, the key innate immune cells in the brain, have been reported to drive brain aging and neurodegenerative disorders; however, few studies have analyzed microglial senescence and the impact of aging on the properties of microglia. In the present study, we characterized senescence- and aging-associated phenotypes of murine brain microglia using well-accepted markers, including telomere length, telomerase activity, expression of p16 INK4a, p21, p53, senescence-associated β-galactosidase, and a senescence-associated secretory phenotype. Quantitative real-time polymerase chain reaction analysis and a Telomeric Repeat Amplification Protocol assay indicated shortened telomeres and increased telomerase activity in senescent microglia, whereas telomeres remained unaltered and telomerase activity was reduced in aged microglia. Senescent microglia upregulated p16 INK4a, p21, and p53, whereas acutely isolated microglia from the aged brain only exhibited a modest upregulation of p16 INK4a. Senescent microglia showed decreased proliferation, while it was unchanged in aged microglia. Furthermore, microglia at late passages strongly upregulated expression of the senescent marker senescence-associated β-galactosidase. Senescent and aged microglia exhibited differential activation profiles and altered responses to stimulation. We conclude that microglia from the aged mouse brain do not show typical senescent changes because their phenotype and functional response strongly differ from those of senescent microglia in vitro.
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An accumulation of senescent microglia with age has been shown in rodents both in vivo and ex vivo, although evidence in aged human brains is limited.
“An accumulation of senescent microglia with age has been shown in rodents both in vivo [72] and ex vivo [51,72], although the evidence of senescent microglia accumulation in aged human brains is limited [42].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [72]
Although p16 is often considered a more reliable marker of senescence, it can also be upregulated in non-senescent contexts.
“Although p16 is often considered a more reliable marker of senescence, it can also be upregulated in non-senescent contexts [18,48,72].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [72]
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- Authors
- Stojiljkovic, M. R., Ain, Q., Bondeva, T., Heller, R., Schmeer, C., & Witte, O. W.
- Affiliations
- Jena University Hospital (DE)
- Corresponding author
- Stojiljkovic, Milan R.
- Witte, Otto W.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 74
- Pages
- 56-69
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2897783256
- Cited by
- 71
- References
- 54
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 11 · 2023: 9 · 2022: 18 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 1
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01GQ0923, 0315581, 16SV7209)
- Deutsche Forschungsgemeinschaft (FO 1738, WI 830/10-2, RTG1715)
- Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft (RegenerAging-FSU-I-03/14)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- microglia, cellular senescence, brain aging, telomere length, telomerase activity, p16INK4a, p21, p53, senescence-associated β-galactosidase, senescence-associated secretory phenotype, microglial proliferation, microglial activation, neuroinflammation, neurodegeneration
- MeSH terms
- Aging, Animals, beta-Galactosidase, Brain, Cells, Cultured, Male, Mice, Inbred C57BL, Up-Regulation, Gene Expression, Telomere, Cellular Senescence, Microglia, Telomerase, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation
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