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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\u2010cell 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\u2010month\u2010old 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\u2010neurogenic effects and on peripheral immune cell presence in the ageing female mouse brain.<\/jats:p>","DOI":"10.1111\/acel.14172","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T04:05:31Z","timestamp":1715745931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Exercise rejuvenates microglia and reverses T cell accumulation in the aged female mouse brain"],"prefix":"10.1111","volume":"23","author":[{"given":"Solal","family":"Chauquet","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience, the University of Queensland  Saint Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily F.","family":"Willis","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The University of Queensland  Saint Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Grice","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, the University of Queensland  Saint Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel B. 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