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Senescent cells accumulate in multiple tissues with aging and at etiological sites of multiple chronic disorders. The senolytic drug combination, Dasatinib plus Quercetin (D+Q), is known to reduce senescent cell abundance in aged mice. However, the effects of long-term D+Q treatment on intestinal senescent cell and inflammatory burden and microbiome composition in aged mice remain unknown. Here, we examine the effect of D+Q on senescence (p16Ink4a and p21Cip1) and inflammation (Cxcl1, Il1\u03b2, Il6, Mcp1, and Tnf\u03b1) markers in small (ileum) and large (caecum and colon) intestine in aged mice (n = 10) compared to age-matched placebo-treated mice (n = 10). Additionally, we examine microbial composition along the intestinal tract in these mice. D+Q-treated mice show significantly lower senescent cell (p16 and p21 expression) and inflammatory (Cxcl1, Il1\u03b2, Il6, Mcp1, and Tnf\u03b1 expression) burden in small and large intestine compared with control mice. Further, we find specific microbial signatures in ileal, cecal, colonic, and fecal regions that are distinctly modulated by D+Q, with modulation being most prominent in small intestine. Further analyses reveal specific correlation of senescence and inflammation markers with specific microbial signatures. Together, these data demonstrate that the senolytic treatment reduces intestinal senescence and inflammation while altering specific microbiota signatures and suggest that the optimized senolytic regimens might improve health via reducing intestinal senescence, inflammation, and microbial dysbiosis in older subjects.<\/jats:p>","DOI":"10.1093\/gerona\/glab002","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:13:13Z","timestamp":1610305993000},"page":"1895-1905","source":"Crossref","is-referenced-by-count":238,"title":["Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-4922","authenticated-orcid":false,"given":"Tatiana Dandolini","family":"Saccon","sequence":"first","affiliation":[{"name":"Department of Nutrition, Federal University of Pelotas, Brazil"},{"name":"Burnet School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Nagpal","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food & Exercise Sciences, Florida State University, Tallahassee, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-1597","authenticated-orcid":false,"given":"Hariom","family":"Yadav","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine-Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"},{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-9731","authenticated-orcid":false,"given":"Marcelo Borges","family":"Cavalcante","sequence":"additional","affiliation":[{"name":"Burnet School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA"},{"name":"Department of Obstetrics and Gynecology, Fortaleza University, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allancer Divino de Carvalho","family":"Nunes","sequence":"additional","affiliation":[{"name":"Burnet School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3410-2860","authenticated-orcid":false,"given":"Augusto","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Federal University of Pelotas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Gesing","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of Ageing, Medical University of Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hughes","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Yousefzadeh","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Tchkonia","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Kirkland","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J","family":"Niedernhofer","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D","family":"Robbins","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8483-930X","authenticated-orcid":false,"given":"Michal M","family":"Masternak","sequence":"additional","affiliation":[{"name":"Burnet School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA"},{"name":"Department of Head and Neck Surgery, Poznan University of Medical Sciences, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"2021101317444912800_CIT0001","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1172\/JCI64125","article-title":"The role of mitochondria in aging","volume":"123","author":"Bratic","year":"2013","journal-title":"J Clin Invest"},{"key":"2021101317444912800_CIT0002","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.cell.2005.01.027","article-title":"Understanding the odd science of aging","volume":"120","author":"Kirkwood","year":"2005","journal-title":"Cell"},{"key":"2021101317444912800_CIT0003","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/nm.4000","article-title":"Cellular senescence in aging and age-related disease: from mechanisms to therapy","volume":"21","author":"Childs","year":"2015","journal-title":"Nat 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mitochondrial and stem cell function and enhances life span in mice","volume":"352","author":"Zhang","year":"2016","journal-title":"Science"},{"key":"2021101317444912800_CIT0008","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","article-title":"Fisetin is a senotherapeutic that extends health and lifespan","volume":"36","author":"Yousefzadeh","year":"2018","journal-title":"EBioMedicine"},{"key":"2021101317444912800_CIT0009","doi-asserted-by":"crossref","first-page":"771","DOI":"10.18632\/aging.101787","article-title":"The curcumin analog EF24 is a novel senolytic agent","volume":"11","author":"Li","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"2021101317444912800_CIT0010","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ebiom.2019.08.069","article-title":"Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney 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