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Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug\u2010inducible \u201csuicide\u201d genes driven by the p16\n                    <jats:italic>\n                      <jats:sup>Ink4a<\/jats:sup>\n                    <\/jats:italic>\n                    promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra\u2010abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity\u2010related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity\u2010related metabolic dysfunction and its complications.\n                  <\/jats:p>","DOI":"10.1111\/acel.12950","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T03:09:36Z","timestamp":1553483376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":634,"title":["Targeting senescent cells alleviates obesity\u2010induced metabolic dysfunction"],"prefix":"10.1111","volume":"18","author":[{"given":"Allyson K.","family":"Palmer","sequence":"first","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic Rochester Minnesota"},{"name":"Medical Scientist Training Program Mayo Clinic Rochester Minnesota"},{"name":"Department of Internal Medicine Mayo Clinic Rochester 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