Cited by 71Neuroinflammation and Neurodegeneration MechanismsTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

Phenotypic and functional differences between senescent and aged murine microglia

Stojiljkovic, Milan R., Ain, Quratul, Bondeva, Tzvetanka, Heller, Regine, Schmeer, Christian, Witte, Otto W.·2019·Neurobiology of Aging

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.

Integrity signals

Registry

Crossref · 10.1016/j.neurobiolaging.2018.10.007

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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].”
  • 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].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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.
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review