Institute for Molecular Bioscience, the University of Queensland, Saint Lucia, Queensland, Australia.
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Saint Lucia, Queensland, Australia.
Aging Cell. 2024 Jul;23(7):e14172. doi: 10.1111/acel.14172. Epub 2024 May 15.
Slowing and/or reversing brain ageing may alleviate cognitive impairments. Previous studies have found that exercise may mitigate cognitive decline, but the mechanisms underlying this remain largely unclear. Here we provide unbiased analyses of single-cell RNA sequencing data, showing the impacts of exercise and ageing on specific cell types in the mouse hippocampus. We demonstrate that exercise has a profound and selective effect on aged microglia, reverting their gene expression signature to that of young microglia. Pharmacologic depletion of microglia further demonstrated that these cells are required for the stimulatory effects of exercise on hippocampal neurogenesis but not cognition. Strikingly, allowing 18-month-old mice access to a running wheel did by and large also prevent and/or revert T cell presence in the ageing hippocampus. Taken together, our data highlight the profound impact of exercise in rejuvenating aged microglia, associated pro-neurogenic effects and on peripheral immune cell presence in the ageing female mouse brain.
减缓或逆转大脑衰老可能会减轻认知障碍。先前的研究发现，运动可以减轻认知能力下降，但这背后的机制在很大程度上仍不清楚。在这里，我们提供了对单细胞 RNA 测序数据的无偏分析，显示了运动和衰老对小鼠海马体特定细胞类型的影响。我们证明，运动对衰老的小胶质细胞有深远而选择性的影响，使它们的基因表达特征恢复为年轻小胶质细胞的特征。小胶质细胞的药理学耗竭进一步表明，这些细胞是运动对海马体神经发生的刺激作用所必需的，但不是认知所必需的。引人注目的是，让 18 个月大的老鼠使用滚轮，在很大程度上也可以防止和/或逆转衰老海马体中 T 细胞的存在。总之，我们的数据强调了运动对衰老小胶质细胞的深刻影响，以及运动对衰老雌性小鼠大脑中与神经发生相关的外周免疫细胞存在的影响。
