{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:11:30Z","timestamp":1791447090849,"version":"4.3.3"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Deterioration of functional capacity mostly determinates frailty in older patients with cardiovascular disease (CVD). Elucidating the pathophysiological mechanisms of physical frailty is an important goal for improving functional health\u2010related outcomes. Our objective was the determination of the transcriptomic signature of physical frailty phenotypes in older patients undergoing cardiac surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients aged \u2265\u200970\u2009years, referred for elective cardiac surgery (e.g., coronary artery bypass graft) or transcatheter aortic valve implantation (TAVI) were recruited. At hospital admission, frailty was assessed based on moderately\/severely impaired mobility (Timed Up and Go; \u2265\u200910 and \u2265\u200920\u2009s), low gait speed (5\u2010m Walk Test; \u2265\u20096\u2009s) or reduced handgrip strength (male \u2264\u200927, female \u2264\u200916\u2009kg). Muscle specimens (<jats:italic>M. quadriceps femoris<\/jats:italic>) were collected during surgery\/intervention and used for total RNA isolation and sequencing. Differential gene expression analysis was performed using DESeq2 and regression analyses investigated association between frailty and gene expression levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010three patients (77.6\u2009\u00b1\u20094.3\u2009years; 74% male) referred to cardiac surgery (<jats:italic>n<\/jats:italic>\u2009=\u200934, 54%) or TAVI (<jats:italic>n<\/jats:italic>\u2009=\u200929, 46%) were included. Overall, 43 patients (70.2%) were characterized as frail by moderately\/severely impaired mobility, 19 (30.6%) by low gait speed and 19 (30.2%) by low handgrip strength. In total, 37 patients (59%) experienced \u2265\u20091 complication (e.g., need of transfusion, atrial fibrillation and delirium); one patient died. Based on transcriptome data, 10 overlapping genes between all physical frailty phenotypes were identified, with <jats:italic>S100A1<\/jats:italic> showing the strongest differences in expression level (e.g., handgrip <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup><jats:sub>adj<\/jats:sub>\u2009=\u20090.579; <jats:italic>p<\/jats:italic>\u2009=\u20090.001). Additional functional studies in C2C12 myoblasts demonstrated the impact of S100A1 on muscle function, and a second independent human cohort confirmed that higher S100A1 blood levels were correlated with increased handgrip strength.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data highlight the potential role of <jats:italic>S100A1<\/jats:italic> in the pathophysiological mechanisms of skeletal muscle impairments in older CVD patients and warrants further consideration as a target gene for physical frailty. These findings also advance our understanding of the genetic and biological factors contributing to frailty, potentially guiding future therapeutic strategies to mitigate its impact on health outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13846","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T08:23:07Z","timestamp":1749111787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptomic Signature of Frailty in Older Patients With Cardiovascular Disease Undergoing Cardiac Surgery or TAVI"],"prefix":"10.1002","volume":"16","author":[{"given":"Omar","family":"Baritello","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Faculty of Health Sciences Brandenburg University of Potsdam  Potsdam Germany"},{"name":"Research Group Molecular and Clinical Life Science of Metabolic Diseases, Faculty of Health Sciences Brandenburg University of Potsdam  Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon\u00a0H.","family":"S\u00fcndermann","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery Deutsches Herzzentrum der Charit\u00e9  Berlin Germany"},{"name":"Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Espinosa\u2010Garnica","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery Deutsches Herzzentrum der Charit\u00e9  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Kempfert","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery Deutsches Herzzentrum der Charit\u00e9  Berlin Germany"},{"name":"Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"J\u00e4hnert","sequence":"additional","affiliation":[{"name":"German Center for Diabetes Research (DZD e.V.), M\u00fcnchen\u2010Neuherberg  Munich Germany"},{"name":"Department of Experimental Diabetology German Institute of Human Nutrition Potsdam\u2010Rehbruecke  Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick\u00a0L.","family":"Beetz","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin  Berlin Germany"},{"name":"Department of Radiology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin BIH Biomedical Innovation Academy, Germany Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Geisel","sequence":"additional","affiliation":[{"name":"Department of Radiology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Gaugel","sequence":"additional","affiliation":[{"name":"Research Group Molecular and Clinical Life Science of Metabolic Diseases, Faculty of Health Sciences Brandenburg University of Potsdam  Potsdam Germany"},{"name":"German Center for Diabetes Research (DZD e.V.), M\u00fcnchen\u2010Neuherberg  Munich Germany"},{"name":"Research Group Nutrigenomics of Obesity German Institute of Human Nutrition Potsdam\u2010Rehbruecke  Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Rominger","sequence":"additional","affiliation":[{"name":"Research Group Molecular and Clinical Life Science of Metabolic Diseases, Faculty of Health Sciences Brandenburg University of Potsdam  Potsdam Germany"},{"name":"German Center for Diabetes Research (DZD e.V.), M\u00fcnchen\u2010Neuherberg  Munich Germany"},{"name":"Research Group Nutrigenomics of Obesity German Institute of Human Nutrition Potsdam\u2010Rehbruecke  Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"M\u00fcller\u2010Werdan","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Medical Gerontology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"Evangelisches Geriatriezentrum Berlin gGmbH  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catrin","family":"Herpich","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Medical Gerontology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"Department of Nutrition and Gerontology German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke  Nuthetal Germany"},{"name":"Institute of Nutritional Science University of Potsdam  Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Norman","sequence":"additional","affiliation":[{"name":"Department of Geriatrics and Medical Gerontology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"},{"name":"Department of Nutrition and Gerontology German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke  Nuthetal Germany"},{"name":"Institute of Nutritional Science University of Potsdam  Nuthetal Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Chadt","sequence":"additional","affiliation":[{"name":"German Center for Diabetes Research (DZD e.V.), M\u00fcnchen\u2010Neuherberg  Munich Germany"},{"name":"Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DDZ), Medical Faculty Heinrich Heine University  Duesseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi","family":"Al\u2010Hasani","sequence":"additional","affiliation":[{"name":"German Center for Diabetes Research (DZD e.V.), M\u00fcnchen\u2010Neuherberg  Munich Germany"},{"name":"Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DDZ), Medical Faculty Heinrich Heine University  Duesseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"V\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Faculty of Health Sciences Brandenburg University of Potsdam  Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Salzwedel","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Faculty of Health Sciences Brandenburg University of Potsdam  Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Vogel","sequence":"additional","affiliation":[{"name":"Research Group Molecular and Clinical Life Science of Metabolic Diseases, Faculty of Health Sciences Brandenburg University of Potsdam  Potsdam Germany"},{"name":"German Center for Diabetes Research (DZD e.V.), M\u00fcnchen\u2010Neuherberg  Munich Germany"},{"name":"Department of Experimental Diabetology German Institute of Human Nutrition Potsdam\u2010Rehbruecke  Nuthetal Germany"},{"name":"Research Group Nutrigenomics of Obesity German Institute of Human Nutrition Potsdam\u2010Rehbruecke  Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO Clinical Consortium on Healthy Ageing \u201cReport of Consortium Meeting 1\u20132 December 2016 in Geneva Switzerland \u201d World Heal. Organ. (2017)."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2021"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101233"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-019-1273-z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.06.039"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.04.068"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13019-021-01541-8"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivu006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2021.813398"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-016-0709-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezy244"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867326666190717152739"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2016.04.005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31785-4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-021-1673-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00771-z"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13459"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165635"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly085"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2018.07.004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw171"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy217"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2022.tb00224.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1519\/JPT.0000000000000162"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-017-1183-1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.064071"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-68797-3"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/crt2.44"},{"issue":"1","key":"e_1_2_8_30_1","first-page":"43","article-title":"Comparing Frailty Markers in Predicting Poor Outcomes After Transcatheter Aortic Valve Replacement","volume":"14","author":"Krishnan A.","year":"2019","journal-title":"Innovations in Technology in Cardiothoracic and Vascular Surgery"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01908"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1400-7"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.11.016"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063205"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2012.8"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu241"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002097"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00370.2010"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010181"},{"issue":"3","key":"e_1_2_8_40_1","first-page":"114","article-title":"Pharmacological Interventions in Frailty and Sarcopenia: Report by the International Conference on Frailty and Sarcopenia Research Task Force","volume":"4","author":"Cesari M.","year":"2015","journal-title":"Journal of Frailty & Aging"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2013.03.022"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2013.11.007"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2012.1397"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13846","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T10:24:03Z","timestamp":1750847043000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jcsm.13846"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13846","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2024-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13846"}}