Hepatic Cellular Senescence Is Attenuated by Filbertone via Modulation of the p53-p21 Pathway in AML12 Hepatocytes

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 (25-100 μM), in both an acute stress-induction model and an established senescent-cell model. p53 and p21 expression, senescence-associated β-galactosidase (SA-β-gal) staining, and the expression of senescence-associated secretory phenotype (SASP)-related cytokines (Il-1β, Il-6, Tnf-α) 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 β-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-1β, Il-6, and Tnf-α, in both stress-induced and established senescent hepatocytes. Conclusions: These findings indicate that filbertone modulates senescence-associated p53-p21 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.