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黑参通过p53-p21/p16通路改善衰老小鼠的细胞衰老。

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

作者信息

Lee Su-Jeong, Lee Da-Yeon, O'Connell Jennifer F, Egan Josephine M, Kim Yoo

机构信息

Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA.

Laboratory of Clinical Investigation, National Institute on Aging (NIA), Baltimore, MD 21224, USA.

出版信息

Biology (Basel). 2022 Jul 25;11(8):1108. doi: 10.3390/biology11081108.

Abstract

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 ( 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.

摘要

细胞衰老作为衰老的标志之一,是指细胞周期的永久性停滞,并且在衰老过程中会加速。黑参(BG)由新鲜人参(C.A. Meyer)经过九次反复蒸制和干燥制成,因其对活性氧(ROS)、炎症和肿瘤发生具有生理益处而受到草药医学的关注,这些都是诱导衰老的常见因素。然而,黑参补充剂调节细胞衰老过程中的哪些关键节点尚未阐明。在本研究中,我们使用体外和衰老小鼠模型研究了黑参对细胞衰老的影响。用黑参处理的原代小鼠胚胎成纤维细胞(MEFs),其衰老由电离辐射(IR)触发,衰老相关β-半乳糖苷酶(SA-β-gal)阳性染色细胞表达较少。在我们对18个月大的衰老小鼠的研究中,补充黑参(300 mg/kg)4周改变了与衰老过程相关的肝脏基因。此外,我们发现补充黑参下调了与年龄相关的炎症基因,尤其是在补体系统中。基于这一观察结果,我们证明补充黑参导致肝脏、骨骼肌和白色脂肪组织等多个代谢器官中经典衰老途径p53依赖的p21和p16的激活减少。因此,我们认为黑参是一种潜在的衰老细胞溶解候选物,可延缓细胞衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ab6/9331701/9e2f58ec1112/biology-11-01108-g001.jpg

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