{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:44:08Z","timestamp":1790271848318,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1IK6BX005238"],"award-info":[{"award-number":["1IK6BX005238"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6 BX005234"],"award-info":[{"award-number":["IK6 BX005234"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["NIA\u2010AG050676"],"award-info":[{"award-number":["NIA\u2010AG050676"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["NIA\u2010AG051442"],"award-info":[{"award-number":["NIA\u2010AG051442"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Oxidative stress and damage are associated with a number of ageing phenotypes, including age\u2010related loss of muscle mass and reduced contractile function (sarcopenia). Our group and others have reported loss of neuromuscular junction (NMJ) integrity and increased denervation as initiating factors in sarcopenia, leading to mitochondrial dysfunction, generation of reactive oxygen species and peroxides, and loss of muscle mass and weakness. Previous studies from our laboratory show that denervation\u2010induced skeletal muscle mitochondrial peroxide generation is highly correlated to muscle atrophy. Here, we directly test the impact of scavenging muscle mitochondrial hydrogen peroxide on the structure and function of the NMJ and muscle mass and function in a mouse model of denervation\u2010induced muscle atrophy CuZnSOD (\n Sod1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice,\n Sod1<\/jats:italic>\n KO).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Whole\u2010body\n Sod1<\/jats:italic>\n KO mice were crossed to mice with increased expression of human catalase (MCAT) targeted specifically to mitochondria in skeletal muscle (mMCAT mice) to determine the impact of reduced hydrogen peroxide levels on key targets of sarcopenia, including mitochondrial function, NMJ structure and function, and indices of muscle mass and function.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Female adult (~12\u2010month\u2010old)\n Sod1<\/jats:italic>\n KO mice show a number of sarcopenia\u2010related phenotypes in skeletal muscle including reduced mitochondrial oxygen consumption and elevated reactive oxygen species generation, fragmentation, and loss of innervated NMJs (\n P<\/jats:italic>\n \u00a0<\u00a00.05), a 30% reduction in muscle mass (\n P<\/jats:italic>\n \u00a0<\u00a00.05), a 36% loss of force generation (\n P<\/jats:italic>\n \u00a0<\u00a00.05), and a loss of exercise capacity (305 vs. 709\u00a0m in wild\u2010type mice,\n P<\/jats:italic>\n \u00a0<\u00a00.05). Muscle from\n Sod1<\/jats:italic>\n KO mice also shows a 35% reduction in sarco(endo)plasmic reticulum ATPase activity (\n P<\/jats:italic>\n \u00a0<\u00a00.05), changes in the amount of calcium\u2010regulating proteins, and altered fibre\u2010type composition. In contrast, increased catalase expression in the mMCAT\u00a0\u00d7\u00a0\n Sod1<\/jats:italic>\n KO mice completely prevents the mitochondrial and NMJ\u2010related phenotypes and maintains muscle mass and force generation. The reduction in exercise capacity is also partially inhibited (~35%,\n P<\/jats:italic>\n \u00a0<\u00a00.05), and the loss of fibre cross\u2010sectional area is inhibited by ~50% (\n P<\/jats:italic>\n \u00a0<\u00a00.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Together, these striking findings suggest that scavenging of mitochondrial peroxide generation by mMCAT expression efficiently prevents mitochondrial dysfunction and NMJ disruption associated with denervation\u2010induced atrophy and weakness, supporting mitochondrial H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n as an important effector of NMJ alterations that lead to phenotypes associated with sarcopenia.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.12768","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T21:09:15Z","timestamp":1632517755000},"page":"1582-1596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Muscle mitochondrial catalase expression prevents neuromuscular junction disruption, atrophy, and weakness in a mouse model of accelerated sarcopenia"],"prefix":"10.1002","volume":"12","author":[{"given":"Hongyang","family":"Xu","sequence":"first","affiliation":[{"name":"Aging & Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rojina","family":"Ranjit","sequence":"additional","affiliation":[{"name":"Aging & Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlan","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology University of Oklahoma Health Sciences Center Oklahoma City OK USA"},{"name":"Oklahoma City VA Medical Center Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0883-0642","authenticated-orcid":false,"given":"Holly","family":"Van Remmen","sequence":"additional","affiliation":[{"name":"Aging & Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City OK USA"},{"name":"Oklahoma City VA Medical Center Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-146308"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e328302f3fe"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/429357a"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.01.036"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70792-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S46826"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106653"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412754111"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.232306"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.19.e27"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00093.2011"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12375"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2257-4_22"},{"key":"e_1_2_9_15_1","volume-title":"Mitochondrial Pathways and Respiratory Control. 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