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Although the inverse correlation between glycative stress and muscle mass and strength has been demonstrated, the underlying molecular mechanisms are not fully understood. This study aimed to elucidate how glycative stress affects the skeletal muscle, particularly the adaptive muscle response to hypertrophic stimuli and its molecular mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL\/6NCr mice were randomly divided into the following two groups: the bovine serum albumin (BSA)\u2010treated and AGE\u2010treated groups. Mice in the AGE\u2010treated group were intraperitoneally administered AGEs (0.5\u00a0mg\/g) once daily, whereas those in the BSA\u2010treated group received an equal amount of BSA (0.5\u00a0mg\/g) as the vehicle control. After 7\u00a0days of continuous administration, the right leg plantaris muscle of mice in each group underwent functional overload treatment by synergist ablation for 7\u00a0days to induce muscle hypertrophy. In in vitro studies, cultured C2C12 myocytes were treated with AGEs (1\u00a0mg\/mL) to examine cell adhesion and cell membrane permeability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Continuous AGE administration increased the levels of fluorescent AGEs, N\u03b5\u2010(carboxymethyl) lysine, and methylglyoxal\u2010derived hydroimidazolone\u20101 in both plasma and skeletal muscle. Plantaris muscle weight, muscle fibre cross\u2010sectional area, protein synthesis rate, and the number of myonuclei increased with functional overload in both groups; however, the increase was significantly reduced by AGE treatment. Some muscles of AGE\u2010treated mice were destroyed by functional overload. Proteomic analysis was performed to explore the mechanisms of muscle hypertrophy suppression and myofibre destruction by AGEs. When principal component analysis was performed on 4659 data obtained by proteomic analysis, AGE treatment was observed to affect protein expression only in functionally overloaded muscles. Enrichment analysis of the 436 proteins extracted using the K\u2010means method further identified a group of proteins involved in cell adhesion. Consistent with this finding, dystrophin\u2013glycoprotein complex proteins and cell adhesion\u2010related proteins were confirmed to increase with functional overload; however, this was attenuated by AGE treatment. Additionally, the treatment of C2C12 muscle cells with AGEs inhibited their ability to adhere and increased cell membrane permeability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study indicates that glycative stress may be a novel pathogenic factor in skeletal muscle dysfunctions by causing loss of membrane integrity and preventing muscle mass gain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13444","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T02:30:50Z","timestamp":1712284250000},"page":"883-896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glycative stress inhibits hypertrophy and impairs cell membrane integrity in overloaded mouse skeletal muscle"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9363-1589","authenticated-orcid":false,"given":"Tatsuro","family":"Egawa","sequence":"first","affiliation":[{"name":"Laboratory of Health and Exercise Sciences, Graduate School of Human and Environmental Studies Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Division of Food Science and Biotechnology, Graduate School of Agriculture Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Kido","sequence":"additional","affiliation":[{"name":"Health and Medical Research Institute National Institute of Advanced Industrial Science and Technology (AIST)  Kagawa Japan"},{"name":"Institute for Physical Activity Fukuoka University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Iyama","sequence":"additional","affiliation":[{"name":"Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Kurogi","sequence":"additional","affiliation":[{"name":"Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumasa","family":"Goto","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Graduate School of Health Sciences Toyohashi SOZO University  Toyohashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"152","article-title":"Glycative stress and anti\u2010aging: 1. 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