Cell senescence – an irreversible proliferation arrest – is one of the possible cellular responses to stress. There is a vast variety of stimuli, extrinsic and intrinsic, known to induce senescence, and several molecular pathways involved in the process; yet much still remains to be explained. Senescent cells can communicate with neighboring cells through secreted factors such as cytokines and chemokines. Several years ago it was shown that cells can also communicate in a more direct manner by an exchange of proteins via cellular bridges (CBs). Recent studies show that in senescent cells the intensity of such transfer increases. The research also revealed that Cdc42 and actin polymerization are indispensable for this process to occur. Here, we evaluate the hypothesis that, apart from actin and Cdc42, also IQGAP1 could be involved in direct intercellular communication. Our results showed that direct transfer occurred preferentially between senescent cells and that IQGAP1 was not essential for this process. Interestingly, cells harboring mutated IQGAP1 had altered morphology and were characterized by decreased proliferation, increased time of division and appearance of some senescence markers (increased activity of senescence-associated β-galactosidase and induction of senescence-associated secretory phenotype). Our findings suggest that IQGAP1 dysfunction can induce senescence.

细胞衰老——一种不可逆的增殖停滞——是一种可能的细胞对压力的反应。有各种各样的刺激，外在的和内在的，已知会诱导衰老，以及参与这个过程的几个分子途径；但仍有许多问题需要解释。衰老细胞可以通过细胞因子和趋化因子等分泌因子与邻近细胞进行交流。几年前，已有研究表明，细胞还可以通过细胞桥 (CB) 进行蛋白质交换，从而以更直接的方式进行交流。最近的研究表明，在衰老细胞中，这种转移的强度增加。研究还表明，Cdc42 和肌动蛋白聚合对于这一过程的发生是必不可少的。在这里，我们评估假设，除了肌动蛋白和 Cdc42，IQGAP1 也可能参与直接的细胞间通讯。我们的结果表明，直接转移优先发生在衰老细胞之间，并且 IQGAP1 对这个过程不是必需的。有趣的是，携带 IQGAP1 突变的细胞的形态发生了改变，其特征是增殖减少、分裂时间增加和一些衰老标志物的出现（衰老相关 β-半乳糖苷酶活性增加和衰老相关分泌表型的诱导）。我们的研究结果表明 IQGAP1 功能障碍可诱导衰老。携带突变 IQGAP1 的细胞具有改变的形态，其特征是增殖减少、分裂时间增加和一些衰老标志物的出现（衰老相关 β-半乳糖苷酶活性增加和衰老相关分泌表型的诱导）。我们的研究结果表明 IQGAP1 功能障碍可诱导衰老。携带突变 IQGAP1 的细胞具有改变的形态，其特征是增殖减少、分裂时间增加和一些衰老标志物的出现（衰老相关 β-半乳糖苷酶活性增加和衰老相关分泌表型的诱导）。我们的研究结果表明 IQGAP1 功能障碍可诱导衰老。