{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:10:24Z","timestamp":1760299824809,"version":"3.41.2"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T00:00:00Z","timestamp":1513814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007\u20102011"],"award-info":[{"award-number":["FP7\/2007\u20102011"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Calorie restriction (<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver\u2010specific responses caused by a diet switch to a medium\u2010fat (<jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>) diet in 24\u2010month\u2010old lifelong, <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine\u2010week\u2010old C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice were exposed either to a control, <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>, or <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> diet. At the age of 24\u00a0months, a subset of mice of the <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> group was transferred to <jats:italic>ad libitum<\/jats:italic><jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> feeding (<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>). The mice were sacrificed at the age of 28\u00a0months, and then, biochemical and molecular analyses were performed. Our results showed that, despite the long\u2010term exposure to the <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> regimen, mice in the <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> group displayed hyperphagia, rapid weight gain, and hepatic steatosis. However, no hepatic fibrosis\/injury or alteration in <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010improved survival was observed in the diet switch group. The liver transcriptomic profile of <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> mice largely shifted to a profile similar to the <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\u2010fed animals but leaving ~22% of the 1,578 differentially regulated genes between the <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> diet groups comparable with the expression of the lifelong <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> group. Therefore, although the diet switch was performed at an old age, the <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\u2010exposed mice showed plasticity in coping with the challenge of a <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> diet without developing severe liver pathologies.<\/jats:p>","DOI":"10.1111\/acel.12696","type":"journal-article","created":{"date-parts":[[2018,3,13]],"date-time":"2018-03-13T08:15:16Z","timestamp":1520928916000},"source":"Crossref","is-referenced-by-count":8,"title":["Plasticity of lifelong calorie\u2010restricted C57<scp>BL<\/scp>\/6J mice in adapting to a medium\u2010fat diet intervention at old age"],"prefix":"10.1111","volume":"17","author":[{"given":"Fenni","family":"Rusli","sequence":"first","affiliation":[{"name":"Division of Human Nutrition, Nutrition, Metabolism &amp; Genomics Group Wageningen University Wageningen The 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University Wageningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aswin L.","family":"Menke","sequence":"additional","affiliation":[{"name":"TNO\u2010Triskelion Zeist The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Institute for Cell and Molecular Biosciences Newcastle University Newcastle Upon Tyne UK"},{"name":"Laboratory of Genetics Wageningen University Wageningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Salvioli","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Franceschi","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine University of 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