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.