[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330936-105":59,"doc-detail-330936-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","cancerous-conditions-accelerate-the-aging-of-skeletal-muscle-via-mitochondrial-dna-damage","Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage","","Skeletal muscle aging and sarcopenia show similar changes in aging-marker levels, yet cancer sarcopenia has rarely been studied through an aging lens. This study assesses aging in cancer sarcopenia and identifies underlying mechanisms in cell and animal models. Mouse aging, in vitro cachexia, and mouse cachexia models reveal comparable alterations in oxidative stress, fibrosis, impaired muscle differentiation, and telomere shortening. Mitochondrial DNA analysis detects a 5 kb deletion and electron-transport-chain complex truncations with reduced OXPHOS. In a mouse cachexia model, HMGB1- and TNFα-neutralizing antibodies lower oxidative stress and prevent mitochondrial DNA deletion, indicating inflammatory cytokines drive mitochondrial oxidative stress that causes mitochondrial DNA damage, reducing OXPHOS and promoting aging.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cancerous-conditions-accelerate-the-aging-of-skeletal-muscle-via-mitochondrial-dna-damage/330936/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cancerous-conditions-accelerate-the-aging-of-skeletal-muscle-via-mitochondrial-dna-damage/330936.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What models were used to study aging in cancer sarcopenia?","Question",{"text":113,"@type":114},"The study used mouse aging, an in vitro cachexia model, and a mouse cachexia model to evaluate changes associated with aging in skeletal muscle.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which skeletal-muscle aging markers were reported to change across models?",{"text":118,"@type":114},"Skeletal muscles showed similar changes in oxidative stress, fibrosis, reduced muscle differentiation potential, and telomere shortening.",{"name":120,"@type":111,"acceptedAnswer":121},"How does mitochondrial DNA damage relate to the proposed mechanism in cancer sarcopenia?",{"text":122,"@type":114},"Inflammatory cytokines trigger mitochondrial oxidative stress, which causes mitochondrial DNA damage; this then decreases OXPHOS and promotes aging, with evidence from HMGB1 and TNFα neutralization reducing oxidative stress and blocking mitochondrial DNA deletion.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},330936,1790095341,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","Article  \nCancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage  \nYi Luo 1,2, Rina Fujiwara-Tani 1,*, Isao Kawahara 1, Kei Goto 1, Shota Nukaga 1, Ryoichi Nishida 1,  \nChie Nakashima 1, Takamitsu Sasaki 1, Yoshihiro Miyagawa 1, Ruiko Ogata 1, Kiyomu Fujii 1, Hitoshi Ohmori 1 and Hiroki Kuniyasu 1, *  \nCitation: Luo, Y.; Fujiwara-Tani, R.; Kawahara, I.; Goto, K.; Nukaga, S.; Nishida, R.; Nakashima, C.; Sasaki, T.; Miyagawa, Y.; Ogata, R.; et al. Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage. Int. J. Mol. Sci. 2024, 25, 7060. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25137060](doi.org/10.3390/ijms25137060)  \n[Academic Editor: Dar](Academic Editor: Dar)ío AcuñaCastroviejo  \nReceived: 29 May 2024  \nRevised: 24 June 2024  \nAccepted: 25 June 2024  \nPublished: 27 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan; [lynantong@hotmail.com](lynantong@hotmail.com) (Y.L.); [isao_kawahara@a011.broada.jp](isao_kawahara@a011.broada.jp) (I.K.); [ilgfgtk@gmail.com](ilgfgtk@gmail.com) (K.G.); [shota.nukaga@gmail.com](shota.nukaga@gmail.com) (S.N.); [g.m__r1@outlook.jp](g.m__r1@outlook.jp) (R.N.); [c-nakashima@naramed-u.ac.jp](c-nakashima@naramed-u.ac.jp) (C.N.); [takamitu@fc4.so-net.ne.jp](takamitu@fc4.so-net.ne.jp) (T.S.); [y.miya1103@gmail.com](y.miya1103@gmail.com) (Y.M.); [pkuma.og824@gmail.com](pkuma.og824@gmail.com) (R.O.); [toto1999-dreamtheater2006-sms@nifty.com](toto1999-dreamtheater2006-sms@nifty.com) (K.F.); [brahmus73@hotmail.com](brahmus73@hotmail.com) (H.O.)  \n2 Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China  \n* Correspondence: [rina_fuji@naramed-u.ac.jp](rina_fuji@naramed-u.ac.jp) (R.F.-T.); [cooninh@zb4.so-net.ne.jp](cooninh@zb4.so-net.ne.jp) (H.K.); Tel.: +81-744-22-3051 (R.F.-T. & H.K.); Fax: +81-744-25-7308 (R.F.-T. & H.K.)  \nAbstract: Skeletal muscle aging and sarcopenia result in similar changes in the levels of aging markers. However, few studies have examined cancer sarcopenia from the perspective of aging. Therefore, this study investigated aging in cancer sarcopenia and explored its causes in vitro and in vivo. In mouse aging, in vitro cachexia, and mouse cachexia models, skeletal muscles showed similar changes in aging markers including oxidative stress, fibrosis, reduced muscle differentiation potential, and telomere shortening. Furthermore, examination of mitochondrial DNA from skeletal muscle revealed a 5 kb deletion in the major arc; truncation of complexes I, IV, and V in the electron transport chain; and reduced oxidative phosphorylation (OXPHOS) . The mouse cachexia model demonstrated high levels of high-mobility group box-1 (HMGB1) and tumor necrosis factor-α (TNFα) in cancer ascites. Continuous administration of neutralizing antibodies against HMGB1 and TNFα in this model reduced oxidative stress and abrogated mitochondrial DNA deletion. These results suggest that in cancer sarcopenia, mitochondrial oxidative stress caused by inflammatory cytokines leads to mitochondrial DNA damage, which in turn leads to decreased OXPHOS and the promotion of aging.  \nKeywords: cancer sarcopenia; aging; mitochondria; mitochondrial DNA  \n1. Introduction  \nCancer cachexia is a multifactorial syndrome characterized by persistent skeletal muscle wasting and weight loss [1] . It can also be considered a metabolic syndrome, as it causes disorders and imbalances in glucose, amino acids, fatty acids, bile acids, ke","cbCaimW92iKioFCr","https://ap.wps.com/l/cbCaimW92iKioFCr","pdf",1354360,15,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What models were used to study aging in cancer sarcopenia?\",\"answer\":\"The study used mouse aging, an in vitro cachexia model, and a mouse cachexia model to evaluate changes associated with aging in skeletal muscle.\"},{\"question\":\"Which skeletal-muscle aging markers were reported to change across models?\",\"answer\":\"Skeletal muscles showed similar changes in oxidative stress, fibrosis, reduced muscle differentiation potential, and telomere shortening.\"},{\"question\":\"How does mitochondrial DNA damage relate to the proposed mechanism in cancer sarcopenia?\",\"answer\":\"Inflammatory cytokines trigger mitochondrial oxidative stress, which causes mitochondrial DNA damage; this then decreases OXPHOS and promotes aging, with evidence from HMGB1 and TNFα neutralization reducing oxidative stress and blocking mitochondrial DNA deletion.\"}]","Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage | PDF",1789990812,38]