Glial Cells and Aging: From the CNS to the Cerebellum
Abstract
1. Introduction
2. Glial Cells in the CNS
2.1. Astrocytes
2.2. Oligodendroglia
2.3. Microglia
3. Cerebellar Glial Cells
3.1. Astrocytes
3.2. Oligodendroglia
3.3. Microglia
4. CNS Aging
4.1. Hallmarks of CNS Aging
4.2. Glial Cell Aging
4.2.1. Astrocytes
4.2.2. WM and Oligodendroglia
4.2.3. Microglia
5. Cerebellar Aging
5.1. Hallmarks of Cerebellar Aging
5.2. Glial Cells Aging
5.2.1. Astrocytes
5.2.2. WM and Oligodendroglia
5.2.3. Microglia
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
List of Full Gene and Protein Names
Genes | |
Abcg1 | ATP Binding Cassette Subfamily G Member 1 |
Aldoc (Zebrin II) | Aldolase C |
Atg7 | Autophagy Related 7 |
Beclin-1 | Beclin 1 |
C3 | Complement Component 3 |
C4b | Complement Component 4B |
Cbln1 | Precerebellin 1 Precursor |
Cdk2 | Cyclin Dependent Kinase 2 |
C-fos | FBJ Murine Osteosarcoma Viral Oncogene |
C-jun | JUN Proto-Oncogene |
Cxcl10 | C-X-C Motif Chemokine Ligand 10 |
Cxcl2 | C-X-C Motif Chemokine Ligand 2 |
Fdps | Farnesyl Diphosphate Synthase |
Gfap | Glial Fibrillary Acidic Protein |
Glul | Glutamate-Ammonia Ligase |
H2-K1 | Histocompatibility 2, K1, K Region |
Hes5 | Hes family bHLH transcription factor 5 |
Hmgcr | 3-Hydroxy-3-Methylglutaryl-CoA Reductase |
Il33 | Interleukin 33 |
Il6 | Interleukin 6 |
Kcnj10 | Potassium Inwardly Rectifying Channel Subfamily J Member 10 |
KRAS | Kirsten Rat Sarcoma Viral Oncogene Homolog |
Lama2 | Laminin Subunit Alpha 2 |
Megf10 | Multiple EGF Like Domains 10 |
Mertk | MER Proto-Oncogene, Tyrosine Kinase |
Mbp | Myelin Basic Protein |
Mag | Myelin Associated Glycoprotein |
Mog | Myelin Oligodendrocyte Glycoprotein |
Mybpc1 | Myosin Binding Protein C1 |
Nol3 | Nucleolar Protein 3 |
Olig1 | Oligodendrocyte Transcription Factor 1 |
Olig-2 | Oligodendrocyte Transcription Factor 2 |
Olig-3 | Oligodendrocyte Transcription Factor 3 |
Pdgfr-a | Platelet Derived Growth Factor Receptor Alpha |
Sept4 | Septin 4 |
Serp3n | Serpin Family 3 Member N |
SHH | Sonic Hedgehog |
Skap2 | Src Kinase Associated Phosphoprotein 2 |
Slc1a2 | Solute Carrier Family 1 Member 2 (EAAT2) |
Slc1a3 | Solute Carrier Family 1 Member 3 (EAAT1) |
Slc6a11 | Solute Carrier Family 6 Member 11 |
Sox2 | SRY-Box Transcription Factor 2 |
Sparc | Secreted Protein Acidic and Rich in Cysteine |
Sqle | Squalene Epoxidase |
Tgfβ2 | Transforming Growth Factor Beta 2 |
Thbs1–4 | Thrombospondin 1 to 4 |
Thbs2 | Thrombospondin 2 |
Vim | Vimentin |
Wif1 | WNT Inhibitory Factor 1 |
Zebrin II | see Aldoc |
Proteins | |
AMPAR | α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor |
APJ | Apelin Receptor |
ApoE | Apolipoprotein E |
AQP4 | Aquaporin 4 |
C3 | Complement Component 3 |
C4b | Complement Component 4B |
CALB | Calbindin |
GABA | Gamma-Aminobutyric Acid |
GLAST | Glutamate Aspartate Transporter |
GLT-1 | Glutamate Transporter 1 |
GJA1 | Gap Junction Alpha-1 Protein (Connexin-43) |
GPR17 | G Protein-Coupled Receptor 17 |
HDACs | Histone Deacetylases |
IP3 | Inositol 1,4,5-trisphosphate |
KIR4.1 | Inward Rectifier Potassium Channel 4.1 |
MAG | Myelin-Associated Glycoprotein |
MBP | Myelin Basic Protein |
MOG | Myelin Oligodendrocyte Glycoprotein |
MYC | MYC Proto-Oncogene |
NG2 | Neural/Glial Antigen 2 |
NIX | BNIP3-Like Protein |
NOTCH | Notch Receptor |
P16INK4A | Cyclin Dependent Kinase Inhibitor 2A |
PARKIN | E3 Ubiquitin-Protein Ligase Parkin |
PDGFRα | Platelet Derived Growth Factor Receptor Alpha |
PINK1 | PTEN-Induced Kinase 1 |
PTCH1/2 | Patched 1 and 2 Receptors |
RYR3 | Ryanodine Receptor 3 |
SA-β-Gal | Senescence-Associated β-Galactosidase |
SHH | Sonic Hedgehog |
STAT1 | Signal Transducer and Activator of Transcription 1 |
TAP1 | Transporter Associated with Antigen Processing 1 |
TDP-43 | TAR DNA Binding Protein 43 |
TAU | Microtubule-Associated Protein Tau |
TGFβ | Transforming Growth Factor Beta |
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Cell Type | Adult CNS Main Functions | Aged CNS Main Changes |
---|---|---|
Astrocytes | - Energy and metabolic homeostasis (lactate, pyruvate, ion regulation) - Synaptic regulation (Ca2+-dependent signaling) - BBB support - Release antioxidants and neurotrophic factors | - Impaired neuronal metabolic support (lipid droplets accumulation, altered fatty acid/cholesterol metabolism) - Altered Ca2+ signaling - Impairment of BBB integrity -Upregulation of GFAP (astroglial reactivity) |
Microglia | - Immune surveillance - Apoptotic cell clearance (phagocytosis) - Neuroprotection - Synaptic remodeling/pruning | - Upregulation of immune/inflammatory genes - Downregulation of homeostatic/phagocytic genes - Morphological dystrophy (reduced ramifications, cytoplasmic swelling, fragmentation) - Senescence-associated phenotype (increased p16INK4A expression, lipofuscin accumulation, SA-b-Gal activity and SASP components) |
OPCs | - Self-renewal (progenitors pool) - Myelin maintenance - Differentiation into OLs for remyelination | - Reduced mitotic activity and differentiation into OLs - Increased susceptibility to senescence signals |
Oligodendrocytes (OLs) | - Myelin synthesis and plasticity - Axonal metabolic support (e.g., K+ homeostasis) - Maintenance of WM integrity | - Decline in myelin regeneration - Altered metabolic support - Altered synaptic activity - Upregulation of immune/inflammatory pathways |
Cell Type | Adult CBL Main Functions | Aged CBL Main Changes |
---|---|---|
Bergmann Glia | - Structural support and maintenance of Purkinje cell (PC) dendrites - Synaptic regulation (Ca2+ dynamics, AMPA/GABA-A receptor response, enwrapment of PC synapses) - Neurotransmitter clearance (glutamate uptake through GLAST, GLT-1; glutamine production) - Ion and metabolic homeostasis (K+ buffering via KIR4.1; water regulation via AQP4; metabolic coupling with PCs) | - Partial reactive phenotype: upregulation of GFAP, SERPIN3n, C3, C4b; mild neuroimmune activation without full A1 profile - Altered Ca2+ dynamics and metabolic fragility: increased spontaneous Ca2+ transients - Disrupted synaptic and glia-neuron interactions: reduced KIR4.1 and GLAST, impaired glutamate clearance, disturbed PC firing precision |
Astrocytes (Velate, Fibrous, Vascular) | - Energy and metabolism homeostasis (e.g., glutamine production, metabolic coupling with PCs) - Regulation of synaptic structure and plasticity - Neurovascular support and BBB integrity - Release of antioxidants and neurotrophic factors | - Reduced cholesterol biosynthesis - Dysregulated glia–neuron interaction - Impairment of BBB integrity and neurovascular uncoupling (astrocyte mislocalization) - Increased expression of immune- and inflammatory-related gene (Gfap, C3, Mhc-I) |
Microglia | - Immune surveillance and phagocytosis (apoptotic cell clearance, especially PCs) - Region-specific transcriptional profile with enriched expression of genes involved in immune alertness (e.g., pathogen recognition, antigen presentation) - Regulation of synaptic refinement (pruning) | - Morphological dystrophy: hypertrophy, process thickening, ramification loss (especially in WM) - Increased CAS genes expression (e.g., those involved in immune/inflammatory pathways) - Increased interferon-responsive and cytokine-mediated signaling - Higher sensitivity to stress and disease-associated degeneration |
OPCs/Oligodendrocytes | - Myelination of PC axons and cerebellar WM - Support of synaptic transmission and circuit precision - Axonal metabolic support (lactate/pyruvate release for energy supply in synergy with astrocytes) | - Structural alterations of cerebellar WM - Loss of myelin integrity and synaptic synchronicity - Poorly characterized oligodendroglial response in aging (limited data compared to cortex) - Potential vulnerability to immune infiltration |
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La Sala, G.; Farini, D. Glial Cells and Aging: From the CNS to the Cerebellum. Int. J. Mol. Sci. 2025, 26, 7553. https://doi.org/10.3390/ijms26157553
La Sala G, Farini D. Glial Cells and Aging: From the CNS to the Cerebellum. International Journal of Molecular Sciences. 2025; 26(15):7553. https://doi.org/10.3390/ijms26157553
Chicago/Turabian StyleLa Sala, Gina, and Donatella Farini. 2025. "Glial Cells and Aging: From the CNS to the Cerebellum" International Journal of Molecular Sciences 26, no. 15: 7553. https://doi.org/10.3390/ijms26157553
APA StyleLa Sala, G., & Farini, D. (2025). Glial Cells and Aging: From the CNS to the Cerebellum. International Journal of Molecular Sciences, 26(15), 7553. https://doi.org/10.3390/ijms26157553