Geroprotective effect of the mitochondrial-targeted antioxidant SkQBerb in a model of chronological aging of human MB135 myoblasts

M. A. Chelombitko, G. V. Morgunova, N. Y. Strochkova, K. G. Lyamzaev
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Abstract

Background. The field of gerontology is actively seeking senolytics and senomorphs that can influence the quantity and activity of senescent cells in the body. Previous studies have demonstrated the geroprotective properties of mitochondrial- directed compounds based on plastoquinone and berberine in various in vitro and in vivo models. Thus, it is plausible that SkQBerb, a mitochondrialtargeted compound combining berberine and plastoquinone, may exhibit higher geroprotective potential compared to previously studied compounds.Objective. The aim of this study is to investigate the geroprotective activity of SkQBerb in a chronological aging model using MB135 myoblasts.Materials and Methods. The effect of SkQBerb on various aging characteristics of human MB135 myoblasts was assessed. Histochemical staining for β-galactosidase was performed using a commercially available kit. The levels of proinflammatory cytokines IL-6 and IL-8 were determined using pre-made immunoassay kits. Additionally, Western blotting was employed to evaluate the levels of p21, pRb (Ser807/811), and LC3B proteins.Results. Analysis of the results revealed that SkQBerb, at concentrations ranging from 20–100 nM, effectively suppressed the accumulation of senescent cells in MB135 cells subjected to chronological aging. Furthermore, it significantly reduced the levels of IL-6 and IL-8, key factors associated with the secretory phenotype.Conclusion. The findings of this study suggest a potential geroprotective and senomorphic effect of SkQBerb. These results open up possibilities for utilizing this mitochondrial-targeted compound as a geroprotector in future applications.
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线粒体靶向抗氧化剂SkQBerb在人MB135成肌细胞时间衰老模型中的衰老保护作用
背景。老年学领域正在积极寻找能够影响体内衰老细胞数量和活性的衰老因子和衰老形态。先前的研究已经在各种体外和体内模型中证明了基于质体醌和小檗碱的线粒体定向化合物的衰老保护作用。因此,与先前研究的化合物相比,SkQBerb是一种结合小檗碱和质体醌的线粒体靶向化合物,可能具有更高的老年保护潜力。本研究的目的是研究SkQBerb在使用MB135成肌细胞的时间衰老模型中的衰老保护活性。材料与方法。评估SkQBerb对人MB135成肌细胞各种衰老特征的影响。使用市售试剂盒进行β-半乳糖苷酶的组织化学染色。使用预先制作的免疫分析试剂盒检测促炎细胞因子IL-6和IL-8的水平。此外,Western blotting检测p21、pRb (Ser807/811)和LC3B蛋白水平。结果表明,SkQBerb在20 ~ 100 nM浓度范围内,可有效抑制MB135细胞衰老细胞的积累。此外,它还显著降低了与分泌表型相关的关键因子IL-6和IL-8的水平。本研究结果提示SkQBerb具有潜在的老年保护和同源性作用。这些结果为在未来的应用中利用线粒体靶向化合物作为老年保护剂开辟了可能性。
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