Microglial senescence: does the brain's immune system have an expiration date?
Abstract
Microglia are seen as the sentries in the CNS who provide a first line of defense whenever there is injury or disease. Microglia and related perivascular macrophages perform various functions, ranging from immunological surveillance to neuroprotection. Recent work in the aged human brain has provided morphological evidence of structural deterioration of microglia, and work in rodents suggests that microglia are subject to replicative senescence (loss of mitotic ability after repeated rounds of replication). Together these observations raise the possibility that old age, and perhaps other factors (genetic and epigenetic) adversely affect viability and self-renewal capacity of microglia, resulting in the generation of senescent and/or dysfunctional cells. Such attrition of the brain's immune system could contribute to the development of neurodegenerative disease by diminishing glial neuroprotection.
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Microglial cells in the ageing brain change structurally and functionally, becoming hyper-responsive to minor stimuli and potentially harming neurons.
“The ageing brain is also characterised by structural and functional changes to microglial cells, which are the resident immune cell population of the central nervous system (CNS) and are the CNS equivalent of macrophages. They are activated by brain injury and local and systemic inflammation and become primed (hyper-responsive) to small stimuli with ageing, which can potentially cause damage and”
From Frailty in elderly people (2013) · cites this paper as [27]
Aged microglia display a dystrophic phenotype, ageing induces a hypersensitive pro-inflammatory primed phenotype, sensome genes are downregulated, and aged microglia express LGALS3, AXL, CLEC7A, MHC class II, and CXCR4 while appearing activated but not polarized.
“Aged microglia display a dystrophic phenotype118–120. It is also known that ageing, similar to neurodegeneration, induces a hypersensitive, pro-inflammatory microglial phenotype that some have referred to as ‘primed microglia’26.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [119]
Microglial senescence plays an important part in the cognitive decline that accompanies ageing.
“References 118 and 119 propose that microglial senescence is important for age-related decline in cognitive function.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [119]
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“With ageing, microglia could further become dystrophic or senescent (Streit, 2006; Streit et al., 2009; Spittau, 2017), unable then to perform efficiently their critical surveillance, immune and physiological roles.”
BackgroundNeuroinflammation in Alzheimer's Disease
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- Authors
- Streit, W. J.
- Affiliations
- University of Florida Health (US)
- Corresponding author
- Streit, Wolfgang J.
- ORCID
- Streit, Wolfgang J.
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 29
- Issue
- 9
- Pages
- 506-510
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W1981310043
- Cited by
- 397
- References
- 42
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 10 · 2023: 15 · 2022: 15 · 2021: 18 · 2020: 22 · 2019: 21 · 2018: 18 · 2017: 18 · 2016: 26 · 2015: 22 · 2014: 23 · 2013: 20 · 2012: 40
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- microglial senescence, replicative senescence, microglia, perivascular macrophages, brain aging, neuroinflammation, neuroprotection, neurodegenerative diseases, immunosenescence
- MeSH terms
- Aging, Animals, Brain, Humans, Cellular Senescence, Microglia
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