Abstract

Astrocyte, the most abundant cell type in the central nervous system, is increasingly recognized and is thought to depend on curial and diverse roles in maintaining brain homeostasis, the blood-brain barrier, secrete neurotrophic factors and regulate synaptic transmission which is essential to tune individual-to-network neuronal activity. Senescence in astrocytes has been discovered to be an important contributor to several age-related neurological diseases like Alzheimer's and Parkinson's disease. However, the latest research about astrocytes from aged subjects is not yet adequate to elucidate their crucial process in the regulation of brain function. In this study, aged mice were housed for 4, 18 and 26 months, and cell model of aged astrocytes was constructed by serial passaging until passage 20–25. Meanwhile, oxidative induced astrocytes senescence model was also constructed by H2O2 induction. Our results indicated that in aged mice, the changes in the morphological structure of mitochondria occurs and in vitro study indicated that aged astrocytes showed manifest changes in several established markers of cellular senescence like P53, P21, the release of inflammatory cytokine IL-6 and SA-β-gal positive cells. Results also showed mitochondrial dysfunction in the oxidative stress-induced astrocytes senescence model and treatment of berberine could ameliorate these alterations. What’s more interests us is that those two types of senescent astrocytes’ conditioned medium co-cultured with neuronal cells could do impact on neuron apoptosis no matter in direct or indirect ways. This study may help us better understand the fundamental role of astrocytes senescence on the regulation of normal and pathological brain aging.