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However, the underlying cellular and molecular pathways remain largely unexplored. To determine whether sepsis leads to long-term persistent muscular consequences and to identify the underlying mechanisms, we used a murine model of reanimated sepsis induced by intraperitoneal injection of a heterologous stool slurry. Muscles were analyzed 3 months later. The oxidative muscle exhibited reduced fatigue resistance and decreased mitochondrial respiration, without a corresponding reduction in mitochondrial OXPHOS proteins. Glycolytic and mixed muscle fibres were atrophied. Markers of oxidative and mitochondrial stress, as well as genes involved in mitochondrial fission, remained present 3 months after sepsis. Low-grade, but significant, muscular inflammation was also measured. Specifically, both the NLRP3 inflammasome and the receptor of Advanced Glycation End-products (RAGE) axis were upregulated. Interestingly, long-term sepsis-induced muscular consequences were not observed in RAGE knockout mice. Overall, we describe for the first time in mice that sepsis causes long-lasting muscle dysfunction after recovery, including mitochondrial alterations and low-grade inflammation, and that RAGE may represent a promising target to mitigate long-term muscle alterations induced by sepsis.<\/jats:p>","DOI":"10.1038\/s41598-025-28645-8","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T14:35:01Z","timestamp":1764340501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RAGE contributes to persistent sepsis-induced muscle and mitochondrial alterations"],"prefix":"10.1038","volume":"15","author":[{"given":"Rapha\u00ebl","family":"Romien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Pierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ducastel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Dubech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Lemaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Grolaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Frimat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Brassart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Bourel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Howsam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Yelnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boulanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Favory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Preau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Lancel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"28645_CR1","doi-asserted-by":"crossref","unstructured":"Gritte, R. 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