{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:08:44Z","timestamp":1793506124496,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18K08063"],"award-info":[{"award-number":["18K08063"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["20H00533"],"award-info":[{"award-number":["20H00533"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ek0210114"],"award-info":[{"award-number":["JP20ek0210114"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20gm1110012"],"award-info":[{"award-number":["JP20gm1110012"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21zf0127003s0201"],"award-info":[{"award-number":["21zf0127003s0201"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Aging"],"DOI":"10.1038\/s43587-021-00151-2","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T12:03:17Z","timestamp":1639137797000},"page":"1117-1126","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":288,"title":["Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice"],"prefix":"10.1038","volume":"1","author":[{"given":"Masayoshi","family":"Suda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ippei","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1291-4814","authenticated-orcid":false,"given":"Goro","family":"Katsuumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohko","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Ikegami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0006-9051","authenticated-orcid":false,"given":"Ryuta","family":"Mikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1468-5170","authenticated-orcid":false,"given":"Jun","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6091-8698","authenticated-orcid":false,"given":"Masahide","family":"Seki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4852-1879","authenticated-orcid":false,"given":"Yutaka","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-8992","authenticated-orcid":false,"given":"Atsushi","family":"Iwama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4494-3601","authenticated-orcid":false,"given":"Hironori","family":"Nakagami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Nagasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-0730","authenticated-orcid":false,"given":"Ryuichi","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7704-8104","authenticated-orcid":false,"given":"Shujiro","family":"Okuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Tsuchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Ozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Nakanishi-Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1627-6151","authenticated-orcid":false,"given":"Tohru","family":"Minamino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"151_CR1","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/nature16932","volume":"530","author":"DJ Baker","year":"2016","unstructured":"Baker, D. J. et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530, 184\u2013189 (2016).","journal-title":"Nature"},{"key":"151_CR2","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1038\/s41591-018-0092-9","volume":"24","author":"M Xu","year":"2018","unstructured":"Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246\u20131256 (2018).","journal-title":"Nat. Med."},{"key":"151_CR3","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1111\/joim.13141","volume":"288","author":"JL Kirkland","year":"2020","unstructured":"Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518\u2013536 (2020).","journal-title":"J. Intern. Med."},{"key":"151_CR4","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.cell.2005.02.003","volume":"120","author":"J Campisi","year":"2005","unstructured":"Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513\u2013522 (2005).","journal-title":"Cell"},{"key":"151_CR5","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/nrd.2017.116","volume":"16","author":"BG Childs","year":"2017","unstructured":"Childs, B. G. et al. Senescent cells: an emerging target for diseases of ageing. Nat. Rev. Drug Discov. 16, 718\u2013735 (2017).","journal-title":"Nat. Rev. Drug Discov."},{"key":"151_CR6","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1161\/01.CIR.0000013836.85741.17","volume":"105","author":"T Minamino","year":"2002","unstructured":"Minamino, T. et al. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation 105, 1541\u20131544 (2002).","journal-title":"Circulation"},{"key":"151_CR7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1161\/01.RES.0000256837.40544.4a","volume":"100","author":"T Minamino","year":"2007","unstructured":"Minamino, T. & Komuro, I. Vascular cell senescence: contribution to atherosclerosis. Circ. Res. 100, 15\u201326 (2007).","journal-title":"Circ. Res."},{"key":"151_CR8","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1038\/nm.2014","volume":"15","author":"T Minamino","year":"2009","unstructured":"Minamino, T. et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat. Med. 15, 1082\u20131087 (2009).","journal-title":"Nat. Med."},{"key":"151_CR9","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.cmet.2014.10.008","volume":"20","author":"I Shimizu","year":"2014","unstructured":"Shimizu, I., Yoshida, Y., Suda, M. & Minamino, T. DNA damage response and metabolic disease. Cell Metab. 20, 967\u2013977 (2014).","journal-title":"Cell Metab."},{"key":"151_CR10","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","volume":"41","author":"T Barrett","year":"2013","unstructured":"Barrett, T. et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res. 41, D991\u2013D995 (2013).","journal-title":"Nucleic Acids Res."},{"key":"151_CR11","doi-asserted-by":"publisher","first-page":"D480","DOI":"10.1093\/nar\/gkm882","volume":"36","author":"M Kanehisa","year":"2008","unstructured":"Kanehisa, M. et al. KEGG for linking genomes to life and the environment. Nucleic Acids Res. 36, D480\u2013D484 (2008).","journal-title":"Nucleic Acids Res."},{"key":"151_CR12","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","volume":"305","author":"A Krogh","year":"2001","unstructured":"Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E. L. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J. Mol. Biol. 305, 567\u2013580 (2001).","journal-title":"J. Mol. Biol."},{"key":"151_CR13","doi-asserted-by":"publisher","first-page":"672","DOI":"10.18632\/aging.100355","volume":"3","author":"SS Jiang","year":"2011","unstructured":"Jiang, S. S. et al. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases. Aging (Albany NY) 3, 672\u2013684 (2011).","journal-title":"Aging (Albany NY)"},{"key":"151_CR14","doi-asserted-by":"publisher","first-page":"e87732","DOI":"10.1172\/jci.insight.87732","volume":"1","author":"M Hashimoto","year":"2016","unstructured":"Hashimoto, M. et al. Elimination of p19(ARF)-expressing cells enhances pulmonary function in mice. JCI Insight 1, e87732 (2016).","journal-title":"JCI Insight"},{"key":"151_CR15","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1111\/acel.12458","volume":"15","author":"CM Roos","year":"2016","unstructured":"Roos, C. M. et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15, 973\u2013977 (2016).","journal-title":"Aging Cell"},{"key":"151_CR16","doi-asserted-by":"publisher","first-page":"e12950","DOI":"10.1111\/acel.12950","volume":"18","author":"AK Palmer","year":"2019","unstructured":"Palmer, A. K. et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell 18, e12950 (2019).","journal-title":"Aging Cell"},{"key":"151_CR17","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.cmet.2019.05.006","volume":"30","author":"C Aguayo-Mazzucato","year":"2019","unstructured":"Aguayo-Mazzucato, C. et al. Acceleration of beta cell aging determines diabetes and senolysis improves disease outcomes. Cell Metab. 30, 129\u2013142.e124 (2019).","journal-title":"Cell Metab."},{"key":"151_CR18","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/ijc.2910600111","volume":"60","author":"MA Weterman","year":"1995","unstructured":"Weterman, M. A. et al. nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. Int. J. Cancer 60, 73\u201381 (1995).","journal-title":"Int. J. Cancer"},{"key":"151_CR19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/jcb.1259","volume":"84","author":"FF Safadi","year":"2001","unstructured":"Safadi, F. F. et al. Cloning and characterization of osteoactivin, a novel cDNA expressed in osteoblasts. J. Cell. Biochem. 84, 12\u201326 (2001).","journal-title":"J. Cell. Biochem."},{"key":"151_CR20","doi-asserted-by":"publisher","first-page":"8125","DOI":"10.1074\/jbc.M008539200","volume":"276","author":"S Shikano","year":"2001","unstructured":"Shikano, S., Bonkobara, M., Zukas, P. K. & Ariizumi, K. Molecular cloning of a dendritic cell-associated transmembrane protein, DC-HIL, that promotes RGD-dependent adhesion of endothelial cells through recognition of heparan sulfate proteoglycans. J. Biol. Chem. 276, 8125\u20138134 (2001).","journal-title":"J. Biol. Chem."},{"key":"151_CR21","doi-asserted-by":"publisher","first-page":"5778","DOI":"10.4049\/jimmunol.179.9.5778","volume":"179","author":"JS Chung","year":"2007","unstructured":"Chung, J. S., Dougherty, I., Cruz, P. D. Jr. & Ariizumi, K. Syndecan-4 mediates the coinhibitory function of DC-HIL on T cell activation. J Immunol 179, 5778\u20135784 (2007).","journal-title":"J Immunol"},{"key":"151_CR22","doi-asserted-by":"publisher","first-page":"4320","DOI":"10.1182\/blood-2006-11-053769","volume":"109","author":"JS Chung","year":"2007","unstructured":"Chung, J. S., Sato, K., Dougherty, I. I., Cruz, P. D. Jr. & Ariizumi, K. DC-HIL is a negative regulator of T lymphocyte activation. Blood 109, 4320\u20134327 (2007).","journal-title":"Blood"},{"key":"151_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/ng794","volume":"30","author":"MG Anderson","year":"2002","unstructured":"Anderson, M. G. et al. Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA\/2J mice. Nat. Genet. 30, 81\u201385 (2002).","journal-title":"Nat. Genet."},{"key":"151_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/srep16920","volume":"5","author":"A Katayama","year":"2015","unstructured":"Katayama, A. et al. Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis. Sci. Rep. 5, 16920 (2015).","journal-title":"Sci. Rep."},{"key":"151_CR25","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nm1214","volume":"11","author":"Y Oike","year":"2005","unstructured":"Oike, Y. et al. Angiopoietin-related growth factor antagonizes obesity and insulin resistance. Nat. Med. 11, 400\u2013408 (2005).","journal-title":"Nat. Med."},{"key":"151_CR26","doi-asserted-by":"publisher","first-page":"E1810","DOI":"10.1152\/ajpendo.00295.2007","volume":"293","author":"T Tchkonia","year":"2007","unstructured":"Tchkonia, T. et al. Increased TNFalpha and CCAAT\/enhancer-binding protein homologous protein with aging predispose preadipocytes to resist adipogenesis. Am. J. Physiol. Endocrinol. Metab. 293, E1810\u2013E1819 (2007).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"151_CR27","doi-asserted-by":"publisher","first-page":"e0001753","DOI":"10.1371\/journal.pone.0001753","volume":"3","author":"N Ieronimakis","year":"2008","unstructured":"Ieronimakis, N., Balasundaram, G. & Reyes, M. Direct isolation, culture and transplant of mouse skeletal muscle derived endothelial cells with angiogenic potential. PLoS ONE 3, e0001753 (2008).","journal-title":"PLoS ONE"}],"container-title":["Nature Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43587-021-00151-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-021-00151-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-021-00151-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T16:54:18Z","timestamp":1670086458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43587-021-00151-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":27,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["151"],"URL":"https:\/\/doi.org\/10.1038\/s43587-021-00151-2","relation":{},"ISSN":["2662-8465"],"issn-type":[{"value":"2662-8465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]},"assertion":[{"value":"26 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}