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Several studies reported an association between sarcopenia-induced cardiac cachexia and poor prognosis in heart disease. However, due to lack of an established animal models, the underlying mechanism of disturbed cardiac repair accompanied with sarcopenia remains poorly understood. Here, we developed a novel sarcopenia-induced cardiac repair disturbance mouse model induced by tail suspension (TS) after cardiac ischemia and reperfusion (I\/R). Importantly, we identified a specific exosomal-microRNA marker, miR-16-5p, in the circulating exosomes of I\/R-TS mice. Of note, sarcopenia after I\/R disturbed cardiac repair and raised the level of circulating-exosomal-miR-16-5p secreting from both the atrophic limbs and heart of TS mice. Likewise, miR-16-5p mimic plasmid disturbed cardiac repair in I\/R mice directly. Additionally, in neonatal rat ventricular myocytes (NRVMs) cultured in vitro under hypoxic conditions in the presence of a miR-16-5p mimic, we observed increased apoptosis through p53 and Caspase3 upregulation, and also clarified that autophagosomes were decreased in NRVMs via SESN1 transcript interference-mediated mTOR activation. In conclusion, we show the pro-apoptotic effect of sarcopenia-derived miR-16-5p, which may be behind the exacerbation of myocardial infarction. Therefore, miR-16-5p can be a novel therapeutic target in the context of cardiac repair disturbances in sarcopenia\u2013cachexia.<\/jats:p>","DOI":"10.1038\/s41598-021-98761-8","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T10:20:00Z","timestamp":1632738000000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sarcopenia-derived exosomal micro-RNA 16-5p disturbs cardio-repair via a pro-apoptotic mechanism in myocardial infarction in mice"],"prefix":"10.1038","volume":"11","author":[{"given":"Taiki","family":"Hayasaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Takehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Aonuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Kano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiwamu","family":"Horiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Kawabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Hasebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"key":"98761_CR1","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1016\/j.amjcard.2015.09.022","volume":"116","author":"A Fach","year":"2015","unstructured":"Fach, A. et al. Comparison of outcomes of patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention analyzed by age groups (<75, 75 to 85, and >85 Years); (Results from the Bremen STEMI Registry). Am. J. Cardiol. 116, 1802\u20131809. https:\/\/doi.org\/10.1016\/j.amjcard.2015.09.022 (2015).","journal-title":"Am. J. Cardiol."},{"key":"98761_CR2","doi-asserted-by":"publisher","first-page":"13F","DOI":"10.1016\/j.amjcard.2006.03.005","volume":"97","author":"RA Weir","year":"2006","unstructured":"Weir, R. A., McMurray, J. J. & Velazquez, E. J. Epidemiology of heart failure and left ventricular systolic dysfunction after acute myocardial infarction: Prevalence, clinical characteristics, and prognostic importance. Am. J. Cardiol. 97, 13F-25F. https:\/\/doi.org\/10.1016\/j.amjcard.2006.03.005 (2006).","journal-title":"Am. J. 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Research on cachexia, sarcopenia and skeletal muscle in cardiology. J. Cachexia Sarcopenia Muscle 3, 219\u2013223. https:\/\/doi.org\/10.1007\/s13539-012-0090-6 (2012).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"98761_CR6","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1002\/jcsm.12118","volume":"7","author":"G Loncar","year":"2016","unstructured":"Loncar, G., Springer, J., Anker, M., Doehner, W. & Lainscak, M. Cardiac cachexia: Hic et nunc. J. Cachexia Sarcopenia Muscle 7, 246\u2013260. https:\/\/doi.org\/10.1002\/jcsm.12118 (2016).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"98761_CR7","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/ajcn\/50.5.1231","volume":"50","author":"IH Rosenberg","year":"1989","unstructured":"Rosenberg, I. H. Summary comments. Am. J. Clin. Nutr. 50, 1231\u20131233 (1989).","journal-title":"Am. J. Clin. 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