Microglial degeneration in the aging brain - bad news for neurons?

Streit, Wolfgang, J.

doi:10.2741/2937

Cited by 150Neuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and TreatmentsGenetics, Aging, and Longevity in Model Organisms

Microglial degeneration in the aging brain - bad news for neurons?

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Streit, Wolfgang, J.·2008·Frontiers in Bioscience

DOI 10.2741/2937

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Abstract

We have long promulgated the idea that microglial cells serve an entirely beneficial role in the central nervous system (CNS), not only as immunological sentinels to fend off potentially dangerous infections, but also as constitutively neuroprotective glia that help sustain neuronal function in the normal and especially in the injured CNS when microglia become activated. In recent years, we have reported on the presence of degenerating microglial cells, which are prominent in the brains of aged humans and humans with neurodegenerative diseases, and this has led us to propose a hypothesis stating that loss of microglia and microglial neuroprotective functions could, at least in part, account for aging-related neurodegeneration. In the current review, we sum up the many aspects that characterize microglial activation and compare them to those that characterize microglial senescence and degeneration. We also consider the possible role of oxidative stress as a cause of microglial degeneration. We finish up by discussing the role microglial cells play in terms of amyloid clearance and degradation with the underlying idea that removal of amyloid constitutes a microglial neuroprotective function, which may become compromised during aging.

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Increased Aβ burden with age suggests microglia become senescent and unable to phagocytose Aβ or their ability becomes latent.
“The increased Aβ burden with age suggests that microglia become senescent and are unable to phagocytose Aβ or that their ability to do so becomes latent [101, 302]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [302]
Section 6 proposes that senescent microglia may become less efficient at phagocytosis, leaving amyloid unremoved, and the paper discusses amyloid clearance as a function that may decline with age. It does not say that aged microglia are unable to phagocytose Aβ or that their ability becomes latent; section 7.1 instead describes microglia actively phagocytosing portions of plaques. The cited passages also do not establish the claim’s premise of an increasing Aβ burden with age. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Animal studies have implicated microglial dysregulation in aging-associated neurogenic and behavioral deficits.
“Animal studies have implicated microglial dysregulation in aging-associated neurogenic and behavioral deficits (Streit et al, 2008).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Streit et al, 2008
Microglial senescence has been associated with increased oxidative stress accumulating over cellular lifespan.
“In addition, microglial senescence has also been associated with increased oxidative stress accumulating over cellular lifespan (Streit et al, 2008).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Streit et al, 2008

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Authors: Streit, W.
Venue: Frontiers in Bioscience
Publisher: IMR Press
Published: 2008
Volume: Volume
Issue: 13
Pages: 3423
ISSN: 1093-4715 (ISSN-L)
1093-9946
DOI: 10.2741/2937
OpenAlex: W1648996057
Cited by: 150
References: 201
Citations by year: 2025: 4 · 2024: 2 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 6 · 2019: 1 · 2018: 10 · 2017: 7 · 2016: 11 · 2015: 14 · 2014: 5 · 2013: 8 · 2012: 12
FWCI: 1.61
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Frontiers in bioscience (publishedVersion)
PubMed (publishedVersion)
Funders: James S. McDonnell Foundation
National Institutes of Health
National Institute on Aging (R01AG023665, AG 023665)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: microglial senescence, microglial activation, brain aging, neurodegeneration, neuroprotection, oxidative stress, amyloid clearance, microglia, neuroinflammation
MeSH terms: Aging, Alzheimer Disease, Animals, Brain, Brain Injuries, Cytosol, Humans, Huntington Disease, Hydrogen Peroxide, Lipofuscin, Nerve Degeneration, Neurons, Parkinson Disease, Cellular Senescence, Microglia, Models, Animal

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Microglial degeneration in the aging brain - bad news for neurons?

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