Neurotoxicants driving glial aging: Role of astrocytic aging in non-cell autonomous neurodegeneration.

Abstract

Astrocytes, the most abundant glial cells in the central nervous system, play essential roles in maintaining neuronal homeostasis, synaptic regulation, and blood-brain barrier integrity. However, these cells can undergo senescence, a cellular state characterized by irreversible growth arrest and the secretion of proinflammatory factors, in response to aging, and pathological stressors, contributing to synaptic dysfunction and neurodegenerative diseases. This review examines the molecular mechanisms driving astrocytic senescence, including oxidative stress, DNA damage, and inflammatory signaling pathways such as NF-κB and the senescence-associated secretory phenotype (SASP). A particular focus is placed on the diverse array of known chemical inducers of astrocyte senescence such as pesticides and heavy metals, which provide critical insights into the processes governing cellular aging in the brain. By analyzing the effects of these inducers, we highlight their implications for neurodegenerative disease progression and brain aging. Understanding astrocytic senescence offers new insights into age-related neuropathology and presents promising avenues for targeted therapies in neurodegenerative disorders induced by environmental toxicants.