Huang Liguo, Chin Lit-Chein, Kimura Koichi, Nakahata Yasukazu
Department of Research & Development, Melsmon Pharmaceutical Co., Ltd., Tokyo 171-0014, Japan.
Department of Neurobiology and Behavior, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
Antioxidants (Basel). 2022 Aug 10;11(8):1545. doi: 10.3390/antiox11081545.
Senescent cells accumulate in the organs of aged animals and exacerbate organ dysfunction, resulting in age-related diseases. Oxidative stress accelerates cellular senescence. Placental extract, used in the alleviation of menopausal symptoms and promotion of wound healing and liver regeneration, reportedly protects against oxidative stress. In this study, we investigated the effects of human placental extract (HPE) on cellular senescence in normal human dermal fibroblasts (NHDFs) under oxidative stress conditions. We demonstrated that HPE delays the onset of cellular senescence. Next-generation sequencing analysis revealed that under oxidative stress conditions, HPE treatment enhanced the expression of the antioxidant genes , , , and . Further, HPE treatment under oxidative stress conditions increased the protein level of nuclear factor-erythroid factor 2-related factor 2 (NRF2)-a vital molecule in the antioxidant pathway-via post-transcriptional and/or post-translational regulations. These findings indicate that HPE treatment in NHDFs, under chronic oxidative stress, delays cellular senescence by mitigating oxidative stress via upregulation of the NRF2-mediated antioxidant pathway, and HPE treatment could potentially ameliorate skin-aging-associated damage, in vivo.
衰老细胞在老年动物的器官中积累，加剧器官功能障碍，导致与年龄相关的疾病。氧化应激会加速细胞衰老。胎盘提取物用于缓解更年期症状、促进伤口愈合和肝脏再生，据报道可抵御氧化应激。在本研究中，我们调查了人胎盘提取物（HPE）在氧化应激条件下对正常人皮肤成纤维细胞（NHDFs）细胞衰老的影响。我们证明HPE可延迟细胞衰老的发生。下一代测序分析显示，在氧化应激条件下，HPE处理可增强抗氧化基因、、、和的表达。此外，在氧化应激条件下进行HPE处理，通过转录后和/或翻译后调控增加了核因子-红细胞系衍生2-相关因子2（NRF2）的蛋白水平，NRF2是抗氧化途径中的关键分子。这些发现表明，在慢性氧化应激下，对NHDFs进行HPE处理可通过上调NRF2介导的抗氧化途径减轻氧化应激，从而延迟细胞衰老，并且HPE处理在体内可能改善与皮肤衰老相关的损伤。
