针对皮肤老化细胞的新疗法

Anna Paszel-Jaworska, Justyna Gornowicz-Porowska, Aleksandra Dańczak-Pazdrowska, Adriana Polańska, Violetta Krajka-Kuźniak, Maciej Stawny, Aleksandra Gostyńska, Michał Masternak, Błażej Rubiś
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引用次数: 0

摘要

衰老伴随着许多过程,这些过程导致细胞代谢改变、细胞周期停滞以及衰老相关分泌表型(SASP)的产生和分泌增加。因此,信号通路级联被激活,导致炎症,从而引发包括癌症在内的多种疾病。近年来,研究人员提出了一种基于抗衰老药物靶向衰老细胞的治疗方法。这类生物活性化合物包括非瑟酮、槲皮素、达沙替尼等。这些化合物通过改善实验动物(啮齿动物)的生活质量,并通过减少不同器官中的衰老细胞池而显着延长寿命,从而对实验动物(啮齿动物)产生影响。基于这些发现,我们决定使用基于人源性角化细胞(HEKa)和成纤维细胞(HDFa)的体外模型来评估这些化合物靶向人类皮肤衰老细胞的潜力。细胞毒性实验表明,化合物的活性不仅与细胞类型有关,而且与时间和剂量有关。进行了进一步的研究,以揭示这些观察的机制方面,包括评估衰老标志物,即p16。然而,在进入临床试验之前,它需要澄清,以提供不仅有效,而且首先是安全的应用于人体皮肤的抗衰老药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
New therapies targeting aging cells in the skin
Senescence is accompanied by numerous processes that lead to alterations in cell metabolism, cell cycle arrest, and, increased production and secretion of senescence-associated secretory phenotype (SASP). Consequently, signaling pathways cascades are activated, leading to inflammation that can trigger multiple disorders, including cancer. Recently, a novel therapeutic approach was proposed based on targeting senescent cells using senolytics. This group of biologically active compounds includes fisetin, quercetin, dasatinib, and others. These compounds were shown to affect laboratory animals (rodents) by improving the quality of life and significantly increasing the length of life by reducing senescent cells pool in different organs. Based on these findings, we decided to evaluate the potential of these compounds in targeting senescent cells in human skin using in vitro model based on human-derived keratinocytes (HEKa) and fibroblasts (HDFa). Cytotoxicity assay revealed that the activity of the compounds was time- and dose-dependent as well as cell-type dependent. Further studies were performed to reveal the mechanistic aspect of these observations including assessment of the senescence marker, namely p16. However, it requires clarification before entering clinical trials to provide not only efficient but, first of all, safe application of senolytics to human skin.
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