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White matter-associated microglia: New players in brain aging and neurodegenerative diseases
Kyusik Ahn1, Seung-Jae Lee2, Inhee Mook-Jung2
1Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
Abstract:
There has been growing interest in brain aging and rejuvenation. It is well known that brain aging is one of the leading causes of neurodegenerative diseases, such as Alzheimer's disease, but brain aging alone can cause cognitive decline. Microglia are thought to act as 'conductors' of white matter aging by modulating diverse glial cells and phagocytosing white matter-derived myelin debris. A recent study identified a specific subpopulation of microglia in the white matter of aged mice, termed white matter-associated microglia (WAM). Additionally, senescent microglia show impaired phagocytic function and altered lipid metabolism, which cause accumulation of lipid metabolites and eventually lead to myelin sheath degeneration. These results suggest that senescent WAM could be pivotal players in axonal loss during brain aging. The aim of this review is to assess the current state of knowledge on brain aging, with an emphasis on the roles of the white matter and microglia, and suggest potential approaches for rejuvenating the aged brain.
Insights
Brain aging accelerates neurodegeneration and cognitive decline. Senescent white matter-associated microglia (WAM) contribute to axonal loss, suggesting they are key targets for brain rejuvenation strategies.
Area of Science:
- Neuroscience
- Aging Research
- Cellular Biology
Background:
- Brain aging is a significant risk factor for neurodegenerative diseases like Alzheimer's and can independently cause cognitive decline.
- Microglia, particularly white matter-associated microglia (WAM), play a crucial role in modulating glial cells and clearing myelin debris during white matter aging.
- Senescent microglia exhibit impaired phagocytosis and altered lipid metabolism, leading to myelin sheath degeneration and axonal loss.
Purpose of the Study:
- To review the current understanding of brain aging, focusing on the roles of white matter and microglia.
- To explore the contribution of senescent white matter-associated microglia (WAM) to axonal loss.
- To propose potential strategies for rejuvenating the aged brain.
Main Methods:
- Literature review of studies on brain aging, white matter, and microglia.
- Analysis of recent findings identifying white matter-associated microglia (WAM) in aged mice.
- Examination of the functional and metabolic changes in senescent microglia.
Main Results:
- Identification of a specific subpopulation of microglia, WAM, in the white matter of aged mice.
- Senescent microglia demonstrate reduced phagocytic capacity and dysregulated lipid metabolism.
- Accumulation of lipid metabolites due to impaired WAM function contributes to myelin sheath degeneration.
Conclusions:
- Senescent WAM are implicated as critical mediators of axonal loss during brain aging.
- Targeting senescent WAM may offer a promising avenue for brain rejuvenation therapies.
- Further research into WAM function is essential for developing interventions against age-related cognitive decline.
