Microglia and the aging brain: are senescent microglia the key to neurodegeneration?
Open accessAbstract
The single largest risk factor for etiology of neurodegenerative diseases like Alzheimer’s disease is increased age. Therefore, understanding the changes that occur as a result of aging is central to any possible prevention or cure for such conditions. Microglia, the resident brain glial population most associated with both protection of neurons in health and their destruction is disease, could be a significant player in age related changes. Microglia can adopt an aberrant phenotype sometimes referred to either as dystrophic or senescent. While aged microglia have been frequently identified in neurodegenerative diseases such as Alzheimer’s disease, there is no conclusive evidence that proves a causal role. This has been hampered by a lack of models of aged microglia. We have recently generated a model of senescent microglia based on the observation that all dystrophic microglia show iron overload. Iron‐overloading cultured microglia causes them to take on a senescent phenotype and can cause changes in models of neurodegeneration similar to those observed in patients. This review considers how this model could be used to determine the role of senescent microglia in neurodegenerative diseases. image
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Altered iron homeostasis has been associated with senescence.
“altered iron homeostasis has been associated with senescence29.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [29]
Microglia are the primary immune cells in the brain that clear pathological substances such as Aβ, but the phagocytosis of Aβ is defective in aged microglia.
“Microglia are the primary immune cells in the brain that clear pathological and redundant substances such as Aβ. However, the phagocytosis of Aβ is defective in aged microglia.178”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [178]
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Zhou, Y., Song, W. M., Andhey, P. S., Swain, A., Levy, T., Miller, K. R., Poliani, P. L., Cominelli, M., Grover, S., Gilfillan, S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0695-9 · Cited by 1,150 · see citing works
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Senescent Microglia: The Key to the Ageing Brain?
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The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases
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- Authors
- Angelova, D. M., & Brown, D. R.
- Affiliations
- University of Bath (GB)
- Corresponding author
- Brown, David R.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2019-10-20
- Volume
- 151
- Issue
- 6
- Pages
- 676-688
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2971440202
- Cited by
- 262
- References
- 142
- Citations by year
- 2026: 24 · 2025: 34 · 2024: 39 · 2023: 49 · 2022: 54 · 2021: 41 · 2020: 20 · 2019: 1
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Pure (University of Bath) (submittedVersion, other-oa)
- Funders
- BRACE
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- microglia, microglial senescence, brain aging, neurodegeneration, Alzheimer's disease, iron overload, age-related risk factors
- MeSH terms
- Aging, Animals, Brain, Humans, Neurons, Cellular Senescence, Microglia, Neurodegenerative Diseases
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.
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