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This results in decreased scientific validity since age is an independent predictor of poor outcome. In this study, we explored the impact of aging on the host response to sepsis using the fecal-induced peritonitis (FIP) model developed by the National Preclinical Sepsis Platform (NPSP).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>C57BL\/6 mice (3 or 12\u00a0months old) were injected intraperitoneally with rat fecal slurry (0.75\u00a0mg\/g) or a control vehicle. To investigate the early stage of sepsis, mice were culled at 4\u00a0h, 8\u00a0h, or 12\u00a0h to investigate disease severity, immunothrombosis biomarkers, and organ injury. Mice received buprenorphine at 4\u00a0h post-FIP. A separate cohort of FIP mice were studied for 72\u00a0h (with buprenorphine given at 4\u00a0h, 12\u00a0h, and then every 12\u00a0h post-FIP and antibiotics\/fluids starting at 12\u00a0h post-FIP). Organs were harvested, plasma levels of Interleukin (IL)-6, IL-10, monocyte chemoattract protein (MCP-1)\/CCL2, thrombin-antithrombin (TAT) complexes, cell-free DNA (CFDNA), and ADAMTS13 activity were quantified, and bacterial loads were measured.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In the 12\u00a0h time course study, aged FIP mice demonstrated increased inflammation and injury to the lungs compared to young FIP mice. In the 72\u00a0h study, aged FIP mice exhibited a higher mortality rate (89%) compared to young FIP mice (42%) (p\u2009&lt;\u20090.001). Aged FIP non-survivors also exhibited a trend towards elevated IL-6, TAT, CFDNA, CCL2, and decreased IL-10, and impaired bacterial clearance compared to young FIP non-survivors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>To our knowledge, this is the first study to investigate the impact of age on survival using the FIP model of sepsis. Our model includes clinically-relevant supportive therapies and inclusion of both sexes. The higher mortality rate in aged mice may reflect increased inflammation and worsened organ injury in the early stage of sepsis. We also observed trends in impaired bacterial clearance, increase in IL-6, TAT, CFDNA, CCL2, and decreased IL-10 and ADAMTS13 activity\u00a0in aged septic non-survivors compared to young septic non-survivors. Our aging model may help to increase the scientific validity of preclinical research and may be useful for identifying mechanisms of age-related susceptibility to sepsis as well as age-specific treatment strategies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40635-024-00609-8","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T15:02:22Z","timestamp":1709910142000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of age on the host response to sepsis in a murine model of fecal-induced peritonitis"],"prefix":"10.1186","volume":"12","author":[{"given":"Neha","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Heinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruva J.","family":"Dwivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj M.","family":"Lalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher A.","family":"Mendelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braedon","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin A.","family":"Kretz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison E.","family":"Fox-Robichaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia C.","family":"Liaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"609_CR1","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1097\/00003246-200107000-00002","volume":"29","author":"DC Angus","year":"2001","unstructured":"Angus DC, Linde-Zwirble WT, Lidicker J et al (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. 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