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In animal models, the most severe outcomes of respiratory infections in older hosts have been associated with an increased burden of senescent cells that accumulate over time with age and create a hyperinflammatory response. Although studies using coronavirus animal models have demonstrated that removal of senescent cells with senolytics, a class of drugs that selectively kills senescent cells, resulted in reduced lung damage and increased survival, little is known about the role that senescent cells play in the outcome of influenza A viral (IAV) infections in aged mice. Here, we tested if the aged mice survival or weight loss IAV infections could be improved using three different senolytic regimens. We found that neither dasatinib plus quercetin, fisetin, nor ABT\u2010263 improved outcomes. Furthermore, both dasatanib plus quercetin and fisetin treatments further suppressed immune infiltration than aging alone. Additionally, our data show that the short\u2010term senolytic agents do not reduce senescent markers in our aged mouse model. These findings suggest that acute senolytic treatments do not universally reverse aging related immune phenotype against all respiratory viral infections.<\/jats:p>","DOI":"10.1111\/acel.14437","type":"journal-article","created":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T07:34:48Z","timestamp":1735976088000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Senolytic treatment attenuates immune cell infiltration without improving <scp>IAV<\/scp> outcomes in aged mice"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0349-7548","authenticated-orcid":false,"given":"Adrian","family":"Luna","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai\u2010Neng","family":"Chou","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Microbiology and Immunology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen M.","family":"Wragg","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"},{"name":"Division of Cardiology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Worley","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikhil","family":"Paruchuri","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muriel G.","family":"Blin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany B.","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Microbiology and Immunology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan","family":"Salmon","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-979X","authenticated-orcid":false,"given":"Daniel R.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan  Ann Arbor Michigan USA"},{"name":"Division of Cardiology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane C.","family":"Deng","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"},{"name":"Veterans Affairs Ann Arbor Healthcare System  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2010.06.004"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010021\u201000114\u20107"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.4.1143"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12592"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe4832"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4010"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/v14071458"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201034593\u2010y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2020.12.003"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010023\u201000442\u2010w"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9363"},{"key":"e_1_2_11_14_1","volume-title":"Number 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