The category of glial cells covers all of the supporting cells of the brain, everything not a neuron, a big tent that includes immune cells such as microglia, the oligodendrocytes that manufacture myelin sheathing for axons, and the sizable astrocyte population, among others. These are very different cell populations with very different functions and behaviors, but all become dysfunctional with age. The present consensus is that glial cell dysfunction is important in aging and neurodegenerative conditions, each population contributing to loss of cognitive function in various ways. Given the size of the topic and the complexity of the brain, a review such as this one can really only skate the surface, however, even when focusing on only one region of the brain.
Among brain regions, the cerebellum (CBL) has traditionally been associated with motor control. However, increasing evidence from connectomics and functional imaging has expanded this view, revealing its involvement in a wide range of cognitive and integrative processes. Despite this emerging relevance, the CBL has received comparatively less attention in aging research, which has focused mainly on other central nervous system (CNS) regions such as the neocortex and hippocampus.
This review synthesizes the current evidence on glial cell aging across the CNS, emphasizing how cerebellar circuits follow distinct trajectories in terms of cellular remodeling, transcriptional reprogramming, and structural vulnerability. Recent findings highlight that cerebellar astrocytes and microglia exhibit specific signatures related to aging compared to their cortical counterpart, including moderate reactivity, selective immune response, and spatial reorganization. Cerebellar white matter (WM) undergoes structural alteration, suggesting that oligodendroglial cells may undergo region-specific alterations, particularly within WM tracts, although these aspects remain underexplored.
Despite the presence of glial remodeling, the CBL maintains a notable degree of structural and functional integrity during aging. This resilience may be the result of the CBL’s ability to maintain synaptic adaptability and homeostatic balance, supported by its highly organized and compartmentalized architecture. A better understanding of the dynamics of cerebellar glial cells in aging may provide new insight into the mechanisms of brain maintenance and identify potential biomarkers for healthy brain aging.
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