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Microglia Phenotypes Converge in Aging and Neurodegenerative Disease

Journal

FRONTIERS IN NEUROLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2021.660720

Keywords

microglia; aging; neurodegeneration; alzheimer' s disease; senescence

Funding

  1. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [403813475, 419157387]
  2. Alzheimer's Association [AARF17-529810]
  3. Alzheimer Forschung Initiative e.V. [20041]

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Microglia, the primary immune cells of the central nervous system, undergo an aging process that impairs their ability to perform vital functions. They transition from a homeostatic state to an activated state in response to insults and aging, showing diverse responses to stimuli such as acute injury or chronic disease. This complexity is further influenced by the distinct alterations that occur in the aging process.
Microglia, the primary immune cells of the central nervous system, hold a multitude of tasks in order to ensure brain homeostasis and are one of the best predictors of biological age on a cellular level. We and others have shown that these long-lived cells undergo an aging process that impedes their ability to perform some of the most vital homeostatic functions such as immune surveillance, acute injury response, and clearance of debris. Microglia have been described as gradually transitioning from a homeostatic state to an activated state in response to various insults, as well as aging. However, microglia show diverse responses to presented stimuli in the form of acute injury or chronic disease. This complexity is potentially further compounded by the distinct alterations that globally occur in the aging process. In this review, we discuss factors that may contribute to microglial aging, as well as transcriptional microglia alterations that occur in old age. We then compare these distinct phenotypic changes with microglial phenotype in neurodegenerative disease.

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