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Specifically, studies have found that exercise effectively inhibits hippocampal neuronal apoptosis, while the molecular mechanism remains unclear. In the present study, we investigated the impact of aerobic exercise on hippocampal neuronal apoptosis in aging mice and the potential involvement of DAPK1 and its downstream pathways based on recent data that DAPK1 may be associated with neuronal death in neurodegenerative diseases. Senescent mice were subjected to 8\u2009weeks of Aerobic training. Following behavioral testing, hippocampal samples were examined histologically and biochemically to detect pathological changes, neuronal apoptosis, and mRNA and protein levels. We found that the exercise intervention improved spatial memory and alleviated neuronal apoptosis in the brain. Notably, exercise down\u2010regulated DAPK1 expression and inhibited Fas death receptor transactivation and the mitochondrial apoptotic pathway in the hippocampus. These results shed new light on the protective effect of regular exercise against brain aging though modulating the DAPK1 pathway.<\/jats:p>","DOI":"10.1096\/fj.202300847rr","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T13:20:06Z","timestamp":1695907206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Aerobic exercise mitigates hippocampal neuronal apoptosis by regulating\n                    <scp>DAPK1<\/scp>\n                    \/\n                    <scp>CDKN2A<\/scp>\n                    \/\n                    <scp>REDD1<\/scp>\n                    \/\n                    <scp>FoXO1<\/scp>\n                    \/\n                    <scp>FasL<\/scp>\n                    signaling pathway in D\u2010galactose\u2010induced aging mice"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7560-7654","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education Hunan Normal University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8019-7441","authenticated-orcid":false,"given":"Wen","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education Hunan Normal University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7209-1079","authenticated-orcid":false,"given":"Si\u2010Lu","family":"Hong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Physical Fitness and Exercise 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