Glial Cells and Aging: From the CNS to the Cerebellum

Abstract

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.

Keywords: Bergmann glia; CBL; CNS-aging; astrocytes heterogeneity; glial cells; microglia; oligodendroglia; white matter.

Figure 1

Hallmarks of CNS aging. The glial cells’ characteristics in adult and healthy older CNSs are schematized. NVU: neurovascular unit; OPC: oligodendrocyte progenitor cell; OL: mature oligodendrocyte.

Figure 2

Hallmarks of the CBL aging. The glial cells characteristics in adult and healthy aged CBL are schematized. Cortical layers of the mature CBL are labeled on the right as follows: ML: molecular layer; PCL: Purkinje cell layer; GL: granule layer; WM: white matter. PC: Purkinje cell; GC: granule cell; BG: Bergman Glia; OPC: oligodendrocyte progenitor cell; OL: mature oligodendrocyte; NVU: Neurovascular unit; CAS: common aging signature. Statements in gray are speculative and derived from pathological models or extrapolated from cortical data, due to limited evidence in the cerebellum.