Cellular senescence is a permanent cell growth arrest that occurs in response to various intrinsic and extrinsic stimuli and is associated with cellular and molecular changes. Long non-coding RNAs (lncRNAs) are key regulators of cellular senescence by affecting the expression of many important genes involved in senescence-associated pathways and processes. Here, we evaluated a panel of lncRNAs associated with senescence for their differential expression between young and senescent human dermal fibroblasts (NHDFs) and studied the effect of a known senomorphic compound, resveratrol, on the expression of lncRNAs in senescent NHDFs. As markers of senescence, we evaluated cell growth, senescence-associated (SA)-β-Gal staining, and the expression of p21, Lamin B1 and γH2AX. We found that H19 and PURPL were the most altered lncRNAs in replicative, in doxorubicin (DOXO) and ionising radiation (IR)-induced senescence models. We then investigated the function of H19 and PURPL in cell senescence by siRNA-mediated silencing in young and senescent fibroblasts, respectively. Our results showed that H19 knockdown reduced cell viability and induced cell senescence and autophagy of NHDFs through the regulation of the PI3K/AKT/mTOR pathway; conversely, PURPL silencing reversed senescence by reducing (SA)-β-Gal staining, recovering cell proliferation with an increase of S-phase cells, and reducing the p53-dependent DNA damage response. Overall, our data highlighted the role of H19 and PURPL in the senescent phenotype and suggested that these lncRNAs may have important implications in senescence-related diseases.

细胞衰老是一种永久性的细胞生长停滞，它是对各种内在和外源性刺激的反应，并与细胞和分子变化有关。长链非编码 RNA （lncRNA） 是细胞衰老的关键调节因子，它影响参与衰老相关途径和过程的许多重要基因的表达。在这里，我们评估了一组与衰老相关的 lncRNAs 在年轻和衰老人真皮成纤维细胞 （NHDF） 之间的差异表达，并研究了已知异形化合物白藜芦醇对衰老 NHDF 中 lncRNA 表达的影响。作为衰老的标志物，我们评估了细胞生长、衰老相关 （SA）-β-Gal 染色以及 p21 、 Lamin B1 和 γH2AX 的表达。我们发现 H19 和 PURPL 是复制、阿霉素 （DOXO） 和电离辐射 （IR） 诱导的衰老模型中改变最大的 lncRNA。然后，我们分别通过 siRNA 介导的年轻和衰老成纤维细胞沉默来研究 H19 和 PURPL 在细胞衰老中的功能。我们的结果表明，H19 敲低通过调节 PI3K/AKT/mTOR 通路降低细胞活力并诱导 NHDF 的细胞衰老和自噬;相反，PURPL 沉默通过减少 （SA）-β-Gal 染色来逆转衰老，随着 S 期细胞的增加而恢复细胞增殖，并减少 p53 依赖性 DNA 损伤反应。总体而言，我们的数据强调了 H19 和 PURPL 在衰老表型中的作用，并表明这些 lncRNAs 可能在衰老相关疾病中具有重要意义。