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Senolytics, agents that selectively eliminate 30%\u201370% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro\u2010inflammatory from their own senescence\u2010associated secretory phenotype (SASP). Consistent with this, a JAK\/STAT inhibitor, Ruxolitinib, which attenuates the pro\u2010inflammatory SASP of senescent human preadipocytes, caused them to become \u201csenolytic\u2010resistant\u201d. Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro\u2010inflammatory. In cell cultures, the 30%\u201370% of human senescent preadipocytes or human umbilical vein endothelial cells (HUVECs) that are senolytic\u2010resistant (to Dasatinib or Quercetin, respectively) had increased p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    , p21\n                    <jats:sup>CIP1<\/jats:sup>\n                    , senescence\u2010associated \u03b2\u2010galactosidase (SA\u03b2gal), \u03b3H2AX, and proliferative arrest similarly to the total SC population (comprising senolytic\u2010sensitive plus\u2010resistant SCs). However, the SASP of senolytic\u2010resistant SCs entailed less pro\u2010inflammatory\/apoptotic factor production, induced less inflammation in non\u2010senescent cells, and was equivalent or richer in growth\/fibrotic factors. Senolytic\u2010resistant SCs released less mitochondrial DNA (mtDNA) and more highly expressed the anti\u2010inflammatory immune evasion signal, glycoprotein non\u2010melanoma\u2010B (GPNMB). Transplanting senolytic\u2010resistant SCs intraperitoneally into younger mice caused less physical dysfunction than transplanting the total SC population. Because Ruxolitinib attenuates SC release of proapoptotic SASP factors, while pathogen\u2010associated molecular pattern factors (PAMPs) can amplify the release of these factors rapidly (acting as \u201csenosensitizers\u201d), senolytic\u2010resistant and senolytic\u2010sensitive SCs appear to be interconvertible.\n                  <\/jats:p>","DOI":"10.1111\/acel.70358","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T05:45:56Z","timestamp":1767073556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Senolytic\u2010Resistant Senescent Cells Have a Distinct\n                    <scp>SASP<\/scp>\n                    Profile and Functional Impact: The Path to Developing Senosensitizers"],"prefix":"10.1111","volume":"25","author":[{"given":"Utkarsh","family":"Tripathi","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-6236","authenticated-orcid":false,"given":"Masayoshi","family":"Suda","sequence":"additional","affiliation":[{"name":"Center for Advanced Gerotherapeutics, Division of Endocrinology and Metabolism Cedars\u2010Sinai Medical Center  Los Angeles California USA"},{"name":"Department of Cardiovascular Biology and Medicine Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vagisha","family":"Kulshreshtha","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan T.","family":"Piatkowski","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson K.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Hospital Internal Medicine, Department of Medicine Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nino","family":"Giorgadze","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Inman","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Gasek","sequence":"additional","affiliation":[{"name":"University of Connecticut  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"University of Connecticut  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt O.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Pirtskhalava","sequence":"additional","affiliation":[{"name":"Center for Advanced Gerotherapeutics, Division of Endocrinology and Metabolism Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0497-2002","authenticated-orcid":false,"given":"Selim","family":"Chaib","sequence":"additional","affiliation":[{"name":"Center for Advanced Gerotherapeutics, Division of Endocrinology and Metabolism Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa P. G.","family":"Langhi Prata","sequence":"additional","affiliation":[{"name":"Center for Advanced Gerotherapeutics, Division of Endocrinology and Metabolism Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renuka","family":"Kandhaya\u2010Pillai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan G.","family":"Tullius","sequence":"additional","affiliation":[{"name":"Division of Transplant Surgery, Department of Surgery Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranya P.","family":"Wyles","sequence":"additional","affiliation":[{"name":"Department of Dermatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rambabu","family":"Majji","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-3054","authenticated-orcid":false,"given":"Hari Krishna","family":"Yalamanchili","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Pediatrics USDA\/ARS Children's Nutrition Research Center, Baylor College of Medicine  Houston Texas 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