Aging is an irreversible biological process that involves oxidative stress, neuroinflammation, and apoptosis, and eventually leads to cognitive dysfunction. However, the underlying mechanisms are not fully understood. In this study, we investigated the role and potential mechanisms of Synaptotagmin-7, a calcium membrane transporter in cognitive impairment in aging mice. Our results indicated that Synaptotagmin-7 expression significantly decreased in the hippocampus of d-galactose-induced or naturally aging mice when compared with healthy controls, as detected by western blot and quantitative reverse transcriptase-polymerase chain reaction analysis. Synaptotagmin-7 overexpression in the dorsal CA1 of the hippocampus reversed long-term potentiation and improved hippocampus-dependent spatial learning in d-galactose-induced aging mice. Synaptotagmin-7 overexpression also led to fully preserved learning and memory in 6-month-old mice. Mechanistically, we demonstrated that Synaptotagmin-7 improved learning and memory by elevating the level of fEPSP and downregulating the expression of aging-related genes such as p53 and p16. The results of our study provide new insights into the role of Synaptotagmin-7 in improving neuronal function and overcoming memory impairment caused by aging, suggesting that Synaptotagmin-7 overexpression may be an innovative therapeutic strategy for treating cognitive impairment.

衰老是一个不可逆的生物学过程，涉及氧化应激、神经炎症和细胞凋亡，最终导致认知功能障碍。然而，潜在的机制尚不完全清楚。在这项研究中，我们研究了 Synaptotagmin-7（一种钙膜转运蛋白）在衰老小鼠认知障碍中的作用和潜在机制。我们的结果表明，与健康对照相比， d-半乳糖诱导或自然衰老小鼠的海马中 Synaptotagmin-7 表达显着降低，通过蛋白质印迹和定量逆转录酶-聚合酶链反应分析检测到。海马背侧 CA1 中突触结合蛋白 7 的过度表达逆转了长期增强并改善了海马依赖的空间学习d-半乳糖诱导的衰老小鼠。Synaptotagmin-7 过度表达也导致 6 个月大的小鼠的学习和记忆完全保留。从机制上讲，我们证明 Synaptotagmin-7 通过提高 fEPSP 的水平和下调与衰老相关的基因（如 p53 和 p16）的表达来改善学习和记忆。我们的研究结果为 Synaptotagmin-7 在改善神经元功能和克服由衰老引起的记忆障碍方面的作用提供了新的见解，表明 Synaptotagmin-7 过表达可能是治疗认知障碍的一种创新治疗策略。