{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:02:09Z","timestamp":1779775329400,"version":"3.53.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008886","name":"Princess Takamatsu Cancer Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008886","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MEXT\/JSPS KAKENHI","award":["25\u00a0K18870"],"award-info":[{"award-number":["25\u00a0K18870"]}]},{"name":"MEXT\/JSPS KAKENHI","award":["19H05740"],"award-info":[{"award-number":["19H05740"]}]},{"name":"MEXT\/JSPS KAKENHI","award":["20H00514"],"award-info":[{"award-number":["20H00514"]}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["21gm5010001"],"award-info":[{"award-number":["21gm5010001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["21\u00a0cm0106175"],"award-info":[{"award-number":["21\u00a0cm0106175"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["21zf0127003"],"award-info":[{"award-number":["21zf0127003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018984","name":"Institute of Medical Science, University of Tokyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018984","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FACS Core Laboratory"},{"name":"Pathology Core Laboratory"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The heart undergoes structural alterations, including fibrosis and cardiomyocyte hypertrophy with age. These alterations are accompanied by functional decline, resulting in heart failure. Although cardiac stromal cells such as fibroblasts and macrophages are known to play a role in age-related cardiac changes, specific subsets of these cells may have a more pronounced effect on the development of these alterations. In this study, we analyzed p16, a marker of senescence,-positive (p16+) cells in cardiac fibrosis by single-cell RNA sequencing of aged p16-Tom mice, in which p16+ cells can be labelled in the presence of tamoxifen. We found that TGF-\u03b2 signalling were significantly enriched in the transcriptome of p16+ fibroblasts compared with p16\u2212 fibroblasts. Besides, BMP4 was upregulated in p16+ fibroblasts. This activation potentially promoted the expression of collagen genes such as Col4a1 and Col5a3. Selective elimination of p16+ fibroblasts ameliorated cardiac fibrosis in aged p16\u2013Col1a2\u2013LRTD mice, with levels comparable to those observed in young mice. These findings suggest that p16+ fibroblasts play a critical role in age-associated cardiac fibrosis. We further demonstrate the potential use of transcriptomic signatures of p16+ fibroblasts to identify human fibroblast subsets causing age-related cardiac diseases such as dilated cardiomyopathy.<\/jats:p>","DOI":"10.1093\/jb\/mvag013","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:19:36Z","timestamp":1771244376000},"page":"413-425","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of p16-positive stromal cells in age-related cardiac disorders"],"prefix":"10.1093","volume":"179","author":[{"given":"Taiki","family":"Morimura","sequence":"first","affiliation":[{"name":"Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo , 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]},{"name":"Project Division of Generative AI Utilization Aging Cells, The Institute of Medical Science, The University of Tokyo , 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teh-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo , 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]},{"name":"Project Division of Generative AI Utilization Aging Cells, The Institute of Medical Science, The University of Tokyo , 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo , 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo , 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"2026052601015271200_ref1","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1161\/01.CIR.0000086898.96021.B9","article-title":"Aging and diseases of the heart","volume":"108","author":"Stern","year":"2003","journal-title":"Circulation"},{"key":"2026052601015271200_ref2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1161\/01.CIR.0000048892.83521.58","article-title":"Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a \u2018set up\u2019 for vascular disease","volume":"107","author":"Lakatta","year":"2003","journal-title":"Circulation"},{"key":"2026052601015271200_ref3","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nature16932","article-title":"Naturally occurring p16Ink4a-positive cells shorten healthy lifespan","volume":"530","author":"Baker","year":"2016","journal-title":"Nature"},{"key":"2026052601015271200_ref4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1126\/science.abb5916","article-title":"Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders","volume":"371","author":"Johmura","year":"2021","journal-title":"Science"},{"key":"2026052601015271200_ref5","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.pharmthera.2009.05.002","article-title":"Cardiac fibroblasts: At the heart of myocardial remodeling","volume":"123","author":"Porter","year":"2009","journal-title":"Pharmacol. 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