{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:47:03Z","timestamp":1792064823539,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Geriatrics Gerontology Int"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Sarcopenia is widely recognized that affects multiple organs, including the cardiovascular system. Clinical studies have consistently shown associations between sarcopenia and vascular aging phenotypes such as vascular calcification, atherosclerosis, and abdominal aortic aneurysms (AAA). However, the molecular mechanisms by which muscle deterioration contributes to vascular degeneration remain poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n To elucidate muscle\u2013vascular crosstalk, we established a murine model combining inflammation\u2010associated muscle atrophy induced by hindlimb immobilization with CaPO\u2084\u2010induced AAA. Vascular degeneration was evaluated by Elastica van Gieson staining for elastic fiber integrity and von Kossa staining for calcification. The role of the muscle\u2010derived myokine irisin was examined through recombinant irisin administration and pharmacological inhibition using the \u03b1V\u03b25 integrin antagonist cilengitide.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Muscle atrophy markedly accelerated vascular calcification and AAA formation in the combined model compared with AAA alone. This was accompanied by enhanced osteogenic phenotype, downregulation of the growth arrest\u2010specific gene 6 (Gas6)\/pAkt survival pathways, and pronounced inflammatory responses in the aortic wall. We found that muscle atrophy significantly reduced muscular and circulating irisin levels. Irisin administration attenuated vascular calcification and AAA progression, whereas irisin signaling inhibition exacerbated these vascular pathologies.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study provides experimental evidence that muscle atrophy directly accelerates vascular calcification and AAA formation. We also identify irisin as a key molecular mediator linking muscle atrophy to vascular degeneration, highlighting muscle\u2010derived signaling as a critical target for preventing vascular pathologies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ggi.70865","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:52:42Z","timestamp":1792061562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immobilzation\u2010Induced Muscle Atrophy Exacerbates Vascular Calcification and Abdominal Aortic Aneurysms Through Irisin Downregulation"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0943-1168","authenticated-orcid":false,"given":"Zehan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2900-6871","authenticated-orcid":false,"given":"Bo\u2010Kyung","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan"},{"name":"Coproduction of Inclusion, Diversity and Equity (IncluDE) Center The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3479-4456","authenticated-orcid":false,"given":"Miya","family":"Oura","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Nanao\u2010Hamai","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6174-7270","authenticated-orcid":false,"given":"Koichi","family":"Toyoshima","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9516-0448","authenticated-orcid":false,"given":"Aya","family":"Komuro","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5935-276X","authenticated-orcid":false,"given":"Sumito","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-7224","authenticated-orcid":false,"given":"Masahiro","family":"Akishita","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute for Geriatrics and Gerontology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/jcsm.13221","article-title":"Sarcopenia and Cardiovascular Diseases: A Systematic Review and Meta\u2010Analysis","volume":"14","author":"Zuo X.","year":"2023","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.cjca.2021.04.002","article-title":"Low Skeletal Muscle Mass Is Associated With the Presence, Incidence, and Progression of Coronary Artery Calcification","volume":"37","author":"Jun J. E.","year":"2021","journal-title":"Canadian Journal of Cardiology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.atherosclerosis.2017.01.005","article-title":"Sarcopenia, but Not Excess Weight or Increased Caloric Intake, Is Associated With Coronary Subclinical Atherosclerosis in the Very Elderly","volume":"258","author":"Campos A. M.","year":"2017","journal-title":"Atherosclerosis"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ejvs.2020.09.020","article-title":"Is There a Correlation Between Sarcopenia and Aortic Aneurysm Morphometry?","volume":"61","author":"Torella F.","year":"2020","journal-title":"European Journal of Vascular and Endovascular Surgery"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2021.743710","article-title":"Relationship Between Sarcopenia and Cardiovascular Diseases in the Elderly: An Overview","volume":"8","author":"He N.","year":"2021","journal-title":"Frontiers in Cardiovascular Medicine"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1\u2010\u03b1\u2010Dependent Myokine That Drives Brown\u2010Fat\u2010Like Development of White Fat and Thermogenesis","volume":"481","author":"Bostr\u00f6m P.","year":"2012","journal-title":"Nature"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1096\/fj.201800178R","article-title":"Inflammation\u2010Induced Lymphatic Architecture and Bone Turnover Changes Are Ameliorated by Irisin Treatment in Chronic Inflammatory Bowel Disease","volume":"32","author":"Narayanan S. 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Implication for Exercise in Obesity","volume":"68","author":"Mazur\u2010Bialy A. I.","year":"2017","journal-title":"Journal of Physiology and Pharmacology"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2022.111676","article-title":"Irisin Reduces Inflammatory Signaling Pathways in Inflammation\u2010Mediated Metabolic Syndrome","volume":"552","author":"Slate\u2010Romano J. J.","year":"2022","journal-title":"Molecular and Cellular Endocrinology"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexmp.2023.104869","article-title":"Inhibition of Integrin Alpha v\/Beta 5 Mitigates the Protective Effect Induced by Irisin in Hemorrhage","volume":"134","author":"Wang L.","year":"2023","journal-title":"Experimental and Molecular Pathology"},{"key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1002\/jcsm.12483","article-title":"Sarcopenia: A Time for Action. An SCWD Position Paper","volume":"10","author":"Bauer J.","year":"2019","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"},{"key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1161\/CIRCULATIONAHA.123.064071","article-title":"Sarcopenia and Cardiovascular Diseases","volume":"147","author":"Damluji A. 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