{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:11:53Z","timestamp":1789441913755,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study investigates p16\/p21 senescence marker heterogeneity in diabetes\u2010related tissues using the p21\u20103MR mouse model, focusing on p16 and p21 as senescence markers. Type 2 diabetes, a common age\u2010related disease, impacts multiple organs; the study examines the heterogeneous distribution of senescence markers in tissues including the pancreas, kidney, heart, adipose tissue, femur, spleen, thymus, liver, and lungs. The results reveal significant spatiotemporal heterogeneity in p16\/p21 co\u2010expression patterns across different organs during diabetes progression, with varying responses to senescent cell clearance treatments. Specifically, the combination of dasatinib and quercetin demonstrated superior reduction in p16\/p21 dual\u2010positive cells in several tissues compared to p21 intervention alone, while p21 intervention showed distinct effects on marker expression in adipose tissue and bone marrow. Immune organs displayed heterogeneity in p16\u2010associated immunosenescence, and the liver and lungs showed greater p16\/p21 expression in vascular niches. This is the first study to use the p21\u20103MR model to explore p16\/p21 marker heterogeneity and differential clearance efficacy of senolytic treatments in diabetic tissues. The findings highlight the need for tissue\u2010specific senolytic strategies, particularly targeting adipocytes and metabolic disorders. Future research should focus on understanding the mechanisms of p21\n                    <jats:sup>high<\/jats:sup>\n                    cell persistence, offering insights for more senescence\u2010targeted treatments.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70127","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T10:55:07Z","timestamp":1760612107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dissecting Spatiotemporal Heterogeneity of Senescence Markers p16\/p21 Across Tissues During Type 2 Diabetes Progression"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7865-0619","authenticated-orcid":false,"given":"Jiayu","family":"Yan","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimei","family":"Yi","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruowen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8442-2339","authenticated-orcid":false,"given":"Junhua","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; 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