{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:44:33Z","timestamp":1785437073533,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002568","name":"University of Ulsan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002568","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02c2f8975","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Cellular senescence refers to a state where the phenotype of cells changes, and the cell cycle comes to a halt. Cellular aging occurs due to various causes and is implicated in the development of various age-related diseases. While the component filbertone in hazelnuts is known for its anti-obesity, anti-neurodegenerative, and anti-inflammatory effects, its potential anti-aging effects have not been elucidated. This study investigated whether filbertone modulates cellular senescence via the tumor suppressor protein p53 and its downstream target p21 in AML12 hepatocytes. Methods: AML12 hepatocytes were treated with doxorubicin or hydrogen peroxide, with or without filbertone (25\u2013100 \u03bcM), in both an acute stress-induction model and an established senescent-cell model. p53 and p21 expression, senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) staining, and the expression of senescence-associated secretory phenotype (SASP)-related cytokines (Il-1\u03b2, Il-6, Tnf-\u03b1) were assessed. Results: The results demonstrated that filbertone dose-dependently reduced the increased p53 and p21, a downstream gene of p53, induced by doxorubicin and hydrogen peroxide. Furthermore, the number of hepatic senescent cells with senescence-associated \u03b2-galactosidase staining was significantly decreased in the presence of filbertone. Filbertone treatment also significantly suppressed the expression of senescence-associated secretory phenotype (SASP)-related pro-inflammatory cytokines, including Il-1\u03b2, Il-6, and Tnf-\u03b1, in both stress-induced and established senescent hepatocytes. Conclusions: These findings indicate that filbertone modulates senescence-associated p53\u2013p21 signaling and the accompanying inflammatory secretory phenotype in an in vitro model of AML12 hepatocytes, suggesting that filbertone may be a geroprotective compound that attenuates cellular senescence.<\/jats:p>","DOI":"10.3390\/nu18142278","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:05:31Z","timestamp":1783929931000},"page":"2278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatic Cellular Senescence Is Attenuated by Filbertone via Modulation of the p53-p21 Pathway in AML12 Hepatocytes"],"prefix":"10.3390","volume":"18","author":[{"given":"Sujung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, University of Ulsan, 93 Daehak-ro, Nam-gu, Ulsan 44610, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9871-5180","authenticated-orcid":false,"given":"Byungyong","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, University of Ulsan, 93 Daehak-ro, Nam-gu, Ulsan 44610, Republic of Korea"},{"name":"Basic-Clinical Convergence Research Institute, University of Ulsan, Ulsan 44610, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/MOG.0000000000000176","article-title":"Aging and liver disease","volume":"31","author":"Kim","year":"2015","journal-title":"Curr. 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