Resveratrol Attenuates H₂O₂-induced Aging and Apoptosis in Mouse Hippocampal Neuron HT22 Cells by Activating Autophagy via the SIRT1/FoxO1 Signaling Pathway

The factors influencing hippocampal aging are complex, and it remains challenging to identify effective anti-aging drugs and reveal pharmacological mechanisms. This study investigates the effects of autophagy mediated by the SIRT1/FoxO1 signaling pathway on resveratrol resistance to H₂O₂-induced aging and apoptosis in mouse hippocampal neurons. HT22 cells were treated with resveratrol and H₂O₂ to evaluate the effects of resveratrol on H₂O₂-induced aging and apoptosis. The levels of P21, P53, BAX, Cleaved Caspase-3, and Bcl-2 were measured to estimate aging and apoptosis. Western blot, immunofluorescence assays, and transmission electron microscopy observation were used to detect the regulation of resveratrol on autophagy. 3-Methyladenine was used to block autophagy, and EX-527 was used to inhibit SIRT1. The changes of autophagy factors and the levels of SIRT1/FoxO1 signaling pathway were assayed. H₂O₂ treatment induced aging in HT22 cells, manifesting increased levels of P21 and P53 and decreased cell viability. H₂O₂ treatment aggravated apoptosis, showing increased levels of BAX and Cleaved Caspase-3, decreased levels of Bcl-2, and increased apoptotic cells. Resveratrol alleviated aging and apoptosis in H₂O₂-induced HT22 cells. Mechanically, resveratrol activated autophagy by up-regulating the levels of LC3B Ⅱ/Ⅰ and Beclin1 and down-regulating P62 against aging and apoptosis, which was abolished by 3-Methyladenine. Western blot results showed resveratrol activated SIRT1/FoxO1 signaling pathway which was related to regulation of autophagy. EX-527 treatment suggested resveratrol could not activate autophagy when the SIRT1/FoxO1 signaling pathway was blocked. These findings indicated that resveratrol activated autophagy via SIRT1/FoxO1 signaling pathway to protect against H₂O₂-induced aging and apoptosis in HT22 cells.