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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-\u03b1 (TNF\u03b1) in cancer ascites. Continuous administration of neutralizing antibodies against HMGB1 and TNF\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms25137060","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T11:19:02Z","timestamp":1719487142000},"page":"7060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage"],"prefix":"10.3390","volume":"25","author":[{"given":"Yi","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"},{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Fujiwara-Tani","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Nukaga","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamitsu","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiko","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyomu","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Ohmori","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-8825","authenticated-orcid":false,"given":"Hiroki","family":"Kuniyasu","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/jcsm.13453","article-title":"Quality of life endpoints in cancer cachexia clinical trials: Systematic review 3 of the cachexia endpoints series","volume":"15","author":"Hjermstad","year":"2024","journal-title":"J. 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