{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:58:51Z","timestamp":1790513931317,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,11,22]],"date-time":"2013-11-22T00:00:00Z","timestamp":1385078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sarcopenia, the age\u2010related, progressive loss of skeletal muscle mass, strength, and function, is a considerable socioeconomic burden by increasing risks of falls, fractures, and frailty. Moreover, sarcopenic patients are often obese and therapeutic options are very limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we assessed the efficacy of espindolol on muscle mass in 19\u2010month\u2010old male Wistar Han rats (weight, 555\u2009\u00b1\u200918\u00a0g), including safety issues. Rats were randomized to treatment with 3\u00a0mg\/kg\/day espindolol (<jats:italic>n<\/jats:italic>\u2009=\u20098) or placebo (<jats:italic>n<\/jats:italic>\u2009=\u200914) for 31\u00a0days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Placebo\u2010treated rats progressively lost body weight (\u221215.5\u2009\u00b1\u20097.2\u00a0g), lean mass (\u22121.5\u2009\u00b1\u20094.2\u00a0g), and fat mass (\u221215.6\u2009\u00b1\u20092.7\u00a0g), while espindolol treatment increased body weight (+8.0\u2009\u00b1\u20096.1\u00a0g, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), particularly lean mass (+43.4\u2009\u00b1\u20093.5\u00a0g, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and reduced fat mass further (\u221238.6\u2009\u00b1\u20093.4\u00a0g, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Anabolic\/catabolic signaling was assessed in gastrocnemius muscle. Espindolol decreased proteasome and caspase\u20103 proteolytic activities by approximately 50\u00a0% (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Western blotting showed a reduced expression of key catabolic regulators, including NF\u03baB, MuRF1, and LC\u20103 (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). The 50\u2010 and 26\u2010kDa forms of myostatin were downregulated fivefold and 20\u2010fold, respectively (both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Moreover, 4E\u2010BP\u20101 was reduced fivefold (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), while phospho\u2010PI3K was upregulated fivefold (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), although Akt expression and phosphorylation were lower compared to placebo (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). No regulation of p38 and expression of ERK1\/2 were observed, while phosphorylation of p38 was reduced (\u221254\u00a0%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and ERK1\/2 was increased (115 and 83\u00a0%, respectively, both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Espindolol did not affect cardiac function (echocardiography) or clinical plasma parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Espindolol reversed the effects of aging\/sarcopenia, particularly loss of muscle mass and increased fat mass. Thus, espindolol is an attractive candidate drug for the treatment of sarcopenia patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Electronic supplementary material<\/jats:title><jats:p>The online version of this article (doi:10.1007\/s13539\u2010013\u20100125\u20107) contains supplementary material.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s13539-013-0125-7","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T18:14:27Z","timestamp":1385057667000},"page":"149-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats"],"prefix":"10.1002","volume":"5","author":[{"given":"Mareike S.","family":"P\u00f6tsch","sequence":"first","affiliation":[{"name":"Applied Cachexia Research, Department of Cardiology Charit\u00e9 Medical School  Berlin"},{"name":"Center for Cardiovascular Research Charit\u00e9 Medical School  Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Tschirner","sequence":"additional","affiliation":[{"name":"Applied Cachexia Research, Department of Cardiology Charit\u00e9 Medical School  Berlin"},{"name":"Center for Cardiovascular Research Charit\u00e9 Medical School  Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Palus","sequence":"additional","affiliation":[{"name":"Applied Cachexia Research, Department of Cardiology Charit\u00e9 Medical School  Berlin"},{"name":"Center for Cardiovascular Research Charit\u00e9 Medical School  Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"von Haehling","sequence":"additional","affiliation":[{"name":"Applied Cachexia Research, Department of Cardiology Charit\u00e9 Medical School  Berlin"},{"name":"Center for Cardiovascular Research Charit\u00e9 Medical School  Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Doehner","sequence":"additional","affiliation":[{"name":"Applied Cachexia Research, Department of Cardiology Charit\u00e9 Medical School  Berlin"},{"name":"Center for Stroke Research Berlin, CSB Charit\u00e9 Medical School  Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Beadle","sequence":"additional","affiliation":[{"name":"PsiOxus Therapeutics  Oxford"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J. 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