Cognitive function progressively declines with advancing age. The aging process can be promoted by obesity and attenuated by exercise. Both conditions affect levels of the chemokine CX3CL1 in peripheral tissues; however, its role in cognitive aging is unknown. In the current study, we administered CX3CL1 into the peritoneal cavity of aged mice to investigate its impact on the aging process. In the peritoneal cavity, CX3CL1 not only reversed the age-associated accumulation of cells expressing the senescence marker p16^INK4a but also increased peritoneal phagocytic activity, indicating that CX3CL1 affected the phenotypes of peritoneal cells. In the hippocampus of aged mice, intraperitoneal administration of CX3CL1 increased the number of Type-2 neural stem cells and promoted brain-derived neurotrophic factor (BDNF) expression. This treatment, furthermore, improved novel object recognition memory impaired with advancing age. Intraperitoneal transplantation of peritoneal cells from CX3CL1-treated aged mice improved novel object recognition memory in recipient aged mice. It indicates that peritoneal cells have a critical role in the CX3CL1-induced improvement of recognition memory in aged mice. Vagotomy inhibited the CX3CL1-induced increase in BDNF expression, demonstrating that the vagus nerve is involved in the hippocampal BDNF expression induced by intraperitoneal administration of CX3CL1. Thus, our results demonstrate that a novel connection among the peritoneal cells, the vagus nerve, and the hippocampus can reverse the age-associated decline in recognition memory.

随着年龄的增长，认知功能逐渐下降。肥胖可以促进衰老过程，运动可以减缓衰老过程。这两种情况都会影响外周组织中趋化因子 CX3CL1 的水平；然而，它在认知老化中的作用尚不清楚。在当前的研究中，我们将 CX3CL1 注入老年小鼠的腹腔，以研究其对衰老过程的影响。在腹膜腔中，CX3CL1 不仅逆转了与年龄相关的细胞表达衰老标记物 p16 ^{INK4a的积累}但也增加了腹膜吞噬活性，表明 CX3CL1 影响了腹膜细胞的表型。在老年小鼠的海马体中，腹膜内注射 CX3CL1 可增加 2 型神经干细胞的数量并促进脑源性神经营养因子 (BDNF) 的表达。此外，这种治疗改善了随着年龄增长而受损的新物体识别记忆。腹膜内移植 CX3CL1 处理的老年小鼠的腹膜细胞可改善受体老年小鼠的新物体识别记忆。这表明腹膜细胞在 CX3CL1 诱导的老年小鼠识别记忆改善中具有关键作用。迷走神经切断术抑制了 CX3CL1 诱导的 BDNF 表达增加，表明迷走神经参与了腹膜内给药 CX3CL1 诱导的海马 BDNF 表达。因此，我们的研究结果表明，腹膜细胞、迷走神经和海马体之间的新联系可以逆转与年龄相关的识别记忆衰退。