Astrocyte Structure-Function Relationship in Senescence and Neurodegeneration

Astrocytes play a critical role in maintaining brain homeostasis by providing metabolic support to neurons, regulating neurotransmitter levels, modulating synaptic transmission, and preserving the blood-brain barrier (BBB) integrity. Aging is associated with the accumulation of senescent astrocytes - cells that have lost their ability to grow and divide but remained metabolically active and resistant to apoptosis. In neurodegenerative diseases, astrocytes develop a reactive phenotype. Both senescent and reactive astrocytes are characterized by distinct secretory phenotypes known for the production of pro-inflammatory cytokines, chemokines, and metalloproteinases, that considerably overlap in both states of astrocytes. Recent studies indicate that the number of senescent astrocytes in the brain directly correlates with the development of neurodegenerative diseases. However, the relationship between senescence and neurodegeneration remains poorly understood. This review examines the similarities and differences in the structural and functional features of astrocytes in senescent and pro-inflammatory states, explores potential interactions between them, analyzes intermediate functional states, and discusses potential mechanisms by which astrocytes of both phenotypes contribute to the development of neurodegenerative diseases.