Objective: Exposure to environmental toxins can negatively impact brain health, and the underlying mechanisms are thought to be oxidative stress and neuroinflammation. Metformin is a medication used as a first-line treatment for type 2 diabetes and also has neuroprotective properties. Senescent astrocytes have been shown to accumulate with age and in the context of many neurodegenerative diseases. The present study investigated the effects of metformin on the oxidative stress-induced premature senescence in astrocyte cells. Material and methods: Primary culture astrocyte cells were pretreated with metformin before the treatment of H2O2 every 72 h. Senescence-associated beta-galactosidase (SA-β-gal) staining was performed to confirm senescence induction, and followed by mRNA expression analysis of cell cycle inhibitors (p53, p21WAF1 and p16 INK4a) and senescence-associated secretory phenotype (SASP) proteins by q-PCR. Intracellular reactive oxygen species (ROS) level was measured by DCFH-DA method. Results: H2O2 significantly increased the number of SA-β-gal positive cells and mRNA levels of cell cycle repressors (p53 and p21WAF1) and SASP proteins (IL-6, IL-1β, CXCL1, and CCL2). Metformin pretreatment significantly reduced H2O2-induced senescent cell number. H2O2–induced increase in levels of p53, p21WAF1, IL-6, CXCL1, and CCL2 mRNA and ROS was significantly inhibited by metformin. Conclusion: In the present study, we show for the first time that metformin significantly prevents premature senescence caused by oxidative stress in astrocyte cells. Metformin prevented H2O2-induced senescence development by decreasing inflammation and oxidative stress and it would be beneficial to support the mechanism of the protective role of metformin on astrocyte senescence in neurodegenerative diseases.
Demir et al. (Fri,) studied this question.