Black Ginseng Ameliorates Cellular Senescence via p53-p21/p16 Pathway in Aged Mice.

Abstract

Simple SummaryThe goal of this study was to examine if BG impacts the aging process, specifically cellular senescence, using in vitro and aged mouse models. Primary mouse embryonic fibroblasts (MEFs) and aged mice (18 months old) showed that BG supplementation retarded cellular senescence. Of note, BG-supplemented aged mice had remarkedly altered hepatic genes involved in the aging process as it caused less activation of the canonical senescence pathway. These observations demonstrated that BG positively impacts the age-related phenotype by controlling the expression of cellular senescence in the liver and other metabolic organs such as skeletal muscle and white adipose tissue.Cellular senescence, one of the hallmarks of aging, refers to permanent cell cycle arrest and is accelerated during the aging process. Black ginseng (BG), prepared by a repeated steaming and drying process nine times from fresh ginseng (Panax ginseng C.A. Meyer), is garnering attention for herbal medicine due to its physiological benefits against reactive oxygen species (ROS), inflammation, and oncogenesis, which are common cues to induce aging. However, which key nodules in the cellular senescence process are regulated by BG supplementation has not been elucidated yet. In this study, we investigated the effects of BG on cellular senescence using in vitro and aged mouse models. BG-treated primary mouse embryonic fibroblasts (MEFs) in which senescence was triggered by ionizing radiation (IR) expressed less senescence-associated β-galactosidase (SA-β-gal)-positive stained cells. In our aged mice (18 months old) study, BG supplementation (300 mg/kg) for 4 weeks altered hepatic genes involved in the aging process. Furthermore, we found BG supplementation downregulated age-related inflammatory genes, especially in the complement system. Based on this observation, we demonstrated that BG supplementation led to less activation of the canonical senescence pathway, p53-dependent p21 and p16, in multiple metabolic organs such as liver, skeletal muscle and white adipose tissue. Thus, we suggest that BG is a potential senolytic candidate that retards cellular senescence.