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- W4225381331 abstract "Cellular senescence, one of the hallmarks of aging, refers to a permanent cell cycle arrest and is accelerated during the aging process. A senolytic, a small molecule that eliminates senescent cells, can be a potential strategy to extend healthy lifespan and ameliorate age-associated diseases. Black ginseng (BG) prepared via nine-times repetitive steaming and drying process from fresh ginseng (Panax ginsengC.A. Meyer) has been reported to its physiological benefits against reactive oxygen species (ROS), inflammation, and oncogenesis which are common cues to induce aging. Therefore, the present study was aimed to investigate the effect of BG on cellular senescence.Senescence-associated β-galactosidase (SA-β-gal) staining was performed on primary mouse embryonic fibroblasts (MEFs) treated 5 μg/mL BG extract for 7 days, and then senescence was induced by γ-ray irradiation (20 Gy). For animal studies, C57BL/6 male mice were divided into three groups: 9-week-old mice orally administered distilled water (Young), 21-month-old mice received administration of distilled water (Old), and aged mice supplemented 300 mg/kg BG extracts (Old + BG). After 4 weeks of daily injection, PCR array and immunoblotting were conducted to evaluate mRNA expression and protein levels of targets associated with cellular senescence and cell cycle regulation in metabolic organs, liver, skeletal muscle (SKM), and white adipose tissue (WAT).In in vitro study, BG treatment reduced the density of SA-β-gal-positive MEFs after γ-ray irradiation (Fig. 1). In aged mice study, BG supplementation remarkedly downregulated age-related hepatic genes, especially in complement component 1q B (C1qb) and C (C1qc), compared to the aged control group. We further examined the canonical Wnt signaling, augmented in a mouse model of accelerated aging, since the complement C1q family activates Wnt signaling by binding to Frizzled receptors. By assessing the related markers, BG supplementation significantly decreased the hepatic β-catenin expression level; it also slightly reduced the levels of glycogen synthase kinase 3β (GSK3β) and its phosphorylated form (p-GSK3β). Recent studies have revealed that Wnt signaling involves in mammalian aging by regulating cell fate and proliferation choice. Thus, we evaluated the expressions of p53 and p21, which involves in cell cycle regulation, and both levels decreased in liver samples from Old + BG group compared to the Old group (Fig. 2). In support of this notion, BG treatment decreased the hepatic mRNA expression levels of senescence-associated secretory phenotypes (SASPs) such as matrix metallopeptidase 12 (Mmp12) and chemokine ligand 2 (Cxcl2). Consistent with the results in the liver, other metabolic organs, SKM and WAT, showed significantly lower p53 expression in Old + BG group over the Old group.The current study indicates that BG could be a potential candidate of senolytics to reversely regulate cellular senescence, resulting from downregulated complement system affecting Wnt signaling pathways and p53/p21 pathway in metabolic organs." @default.
- W4225381331 created "2022-05-05" @default.
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- W4225381331 date "2022-05-01" @default.
- W4225381331 modified "2023-09-27" @default.
- W4225381331 title "Black ginseng ameliorates cellular senescence via p53/p21 pathway" @default.
- W4225381331 doi "https://doi.org/10.1096/fasebj.2022.36.s1.r5925" @default.
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