{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:01:29Z","timestamp":1787500889369,"version":"build-2736575974"},"reference-count":72,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["T32 CA211036"],"award-info":[{"award-number":["T32 CA211036"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Aging is associated with increased susceptibility to metabolic stress and chronic liver disease, yet the interactions between age and metabolic stressors and the potential for ameliorating interventions remain incompletely understood. Here, we examined the hepatic response of young (7\u2010month\u2010old) and old (25\u2010month\u2010old) C57BL\/6 male mice to a 9\u2010week high\u2010fat diet (HFD) and assessed whether rapamycin, a well\u2010established pro\u2010longevity intervention, could mitigate age\u2010exacerbated effects. While both age groups developed metabolic\u2010associated steatohepatitis (MASH), older mice displayed more severe hepatic steatosis, inflammation, and transcriptional dysregulation. Transcriptomic profiling of whole livers and purified hepatocytes revealed that aging amplifies HFD\u2010induced inflammatory and metabolic gene expression changes, including activation of immune pathways and suppression of metabolic pathways. Notably, treatment of aging mice with rapamycin reversed the majority of HFD\u2010driven transcriptional alterations, including upregulation of pro\u2010inflammatory regulators such as Stat1, and dysregulation of metabolic gene networks. Rapamycin also reduced hepatosteatosis, total body weight, and a tumorigenic transcriptomic signature associated with hepatocellular carcinoma risk. These findings demonstrate that aging intensifies hepatic sensitivity to dietary metabolic stress and identify rapamycin as a promising therapeutic to counteract age\u2010related liver dysfunction and metabolic dysfunction\u2010associated steatotic liver disease (MASLD) progression.<\/jats:p>","DOI":"10.1111\/acel.70395","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T15:18:57Z","timestamp":1770477537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rapamycin Reverses the Hepatic Response to Diet\u2010Induced Metabolic Stress That Is Amplified by Aging"],"prefix":"10.1111","volume":"25","author":[{"given":"Aaron","family":"Havas","sequence":"first","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute  La Jolla California 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