{"title":"以网络为基础系统分析运动对老年人骨质疏松的抑制作用","authors":"Hirotaka Iijima, Fabrisia Ambrosio, Yusuke Matsui","doi":"10.1113/JP285349","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n \n <div>Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise <i>versus</i> immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed <i>Pgc-1α</i> as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated <i>in silico</i> and <i>in situ</i> approaches to induce <i>Pgc-1α</i> overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the <i>Pgc-1α</i>–mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age-related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations.\n\n <figure>\n <div><picture>\n <source></source></picture><p></p>\n </div>\n </figure>\n </div>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>Fat accumulation is a quintessential feature of aged skeletal muscle.</li>\n \n <li>While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined.</li>\n \n <li>This study implemented a series of network medicine approaches and uncovered <i>Pgc-1α</i> as a mechanistic driver of the regulation of fibro-adipogenic progenitors (FAPs) by physical activity.</li>\n \n <li>Integrated <i>in silico</i> and <i>in situ</i> approaches to induce <i>Pgc-1α</i> overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis.</li>\n \n <li>Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of <i>Pgc-1α</i>-mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 1","pages":"45-67"},"PeriodicalIF":4.7000,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP285349","citationCount":"0","resultStr":"{\"title\":\"Network-based systematic dissection of exercise-induced inhibition of myosteatosis in older individuals\",\"authors\":\"Hirotaka Iijima, Fabrisia Ambrosio, Yusuke Matsui\",\"doi\":\"10.1113/JP285349\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n \\n <div>Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise <i>versus</i> immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed <i>Pgc-1α</i> as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated <i>in silico</i> and <i>in situ</i> approaches to induce <i>Pgc-1α</i> overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the <i>Pgc-1α</i>–mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age-related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations.\\n\\n <figure>\\n <div><picture>\\n <source></source></picture><p></p>\\n </div>\\n </figure>\\n </div>\\n </section>\\n \\n <section>\\n \\n <h3> Key points</h3>\\n \\n <div>\\n <ul>\\n \\n <li>Fat accumulation is a quintessential feature of aged skeletal muscle.</li>\\n \\n <li>While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined.</li>\\n \\n <li>This study implemented a series of network medicine approaches and uncovered <i>Pgc-1α</i> as a mechanistic driver of the regulation of fibro-adipogenic progenitors (FAPs) by physical activity.</li>\\n \\n <li>Integrated <i>in silico</i> and <i>in situ</i> approaches to induce <i>Pgc-1α</i> overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis.</li>\\n \\n <li>Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of <i>Pgc-1α</i>-mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":50088,\"journal\":{\"name\":\"Journal of Physiology-London\",\"volume\":\"603 1\",\"pages\":\"45-67\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2023-12-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP285349\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Physiology-London\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1113/JP285349\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Physiology-London","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1113/JP285349","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Network-based systematic dissection of exercise-induced inhibition of myosteatosis in older individuals
Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed Pgc-1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated in silico and in situ approaches to induce Pgc-1α overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the Pgc-1α–mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age-related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations.
Key points
Fat accumulation is a quintessential feature of aged skeletal muscle.
While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined.
This study implemented a series of network medicine approaches and uncovered Pgc-1α as a mechanistic driver of the regulation of fibro-adipogenic progenitors (FAPs) by physical activity.
Integrated in silico and in situ approaches to induce Pgc-1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis.
Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of Pgc-1α-mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis.
期刊介绍:
The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew.
The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.