{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:11:09Z","timestamp":1791033069718,"version":"4.1.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Rejuvenation Research"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>\n                    It has been suggested that increasing age is correlated with an acceleration of the progression of liver fibrosis induced by various agents, such as hepatitis C virus or chronic alcohol consumption. However, the cellular and molecular changes underlying this predisposition are not entirely understood. In the context of an aging population, it becomes challenging to decipher the mechanisms responsible for this higher susceptibility of older individuals to this acquired liver disorder. To address this issue, we induced liver fibrosis by carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) chronic administration to 8-week- and 15-month-old mice. We confirmed that susceptibility to fibrosis development increased with age and showed that aging did not affect fibrosis resolution capacity. We then focused on the impairment of hepatocyte proliferation, oxidative stress, and inflammation as potential mechanisms accelerating the development of fibrosis in the elderly. We detected no inhibition of hepatocyte proliferation after CCl\n                    <jats:sub>4<\/jats:sub>\n                    injury in 15-month-old mice, whereas it was inhibited after a partial hepatectomy. Finally, we observed that, in a context in which liver oxidative stress was not differentially increased in both experimental groups, there was a higher recruitment of inflammatory cells, including mostly macrophages and lymphocytes, oriented toward a T helper 2 (T\n                    <jats:sub>H<\/jats:sub>\n                    2) response in older mice. Our data show that in conditions of equivalent levels of oxidative stress and maintained hepatocyte proliferative capacity, an increased inflammatory reaction mainly composed of CD4\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes and macrophages expressing T\n                    <jats:sub>H<\/jats:sub>\n                    2 cytokines is the main factor involved in the higher susceptibility to fibrosis with increasing age.\n                  <\/jats:p>","DOI":"10.1089\/rej.2010.1146","type":"journal-article","created":{"date-parts":[[2011,5,6]],"date-time":"2011-05-06T14:30:36Z","timestamp":1304692236000},"page":"353-363","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":43,"title":["Increased Susceptibility to Liver Fibrosis with Age Is Correlated with an Altered Inflammatory Response"],"prefix":"10.1177","volume":"14","author":[{"given":"Meriem","family":"Mahrouf-Yorgov","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM)","place":["France"]},{"name":"CNRS (UMR 8104), Paris, France."},{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Collin","family":"de l'Hortet","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM)","place":["France"]},{"name":"CNRS (UMR 8104), Paris, France."},{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Cosson","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie, H\u00f4pital Bic\u00eatre, AP-HP, Kremlin Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhamid","family":"Slama","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie, H\u00f4pital Bic\u00eatre, AP-HP, Kremlin Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Abdoun","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM)","place":["France"]},{"name":"CNRS (UMR 8104), Paris, France."},{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques-Emmanuel","family":"Guidotti","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM)","place":["France"]},{"name":"CNRS (UMR 8104), Paris, France."},{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Fromenty","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes 1","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM)","place":["France"]},{"name":"CNRS (UMR 8104), Paris, France."},{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Gilgenkrantz","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM)","place":["France"]},{"name":"CNRS (UMR 8104), Paris, France."},{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2893.1997.00054.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)07642-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)00097-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.2.248"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290301"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70364-7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.33993"},{"key":"e_1_3_3_9_2","first-page":"713","article-title":"Risk factors and prognosis in primary biliary cirrhosis","volume":"84","author":"Goudie BM","year":"1989","unstructured":"Goudie BM, , Burt AD, , Macfarlane GJ, , Boyle P, , Gillis CR, , MacSween RN, , Watkinson G. 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Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. 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