It is well established that inflammation in the body promotes organism aging, and recent studies have attributed a similar effect to senescent cells. Considering that certain pro‐inflammatory cytokines can induce cellular senescence, systematically evaluating the effects of pro‐inflammatory cytokines in cellular senescence is an important and urgent scientific problem, especially given the ongoing surge in aging human populations. Treating IMR90 cells and HUVECs with pro‐inflammatory cytokines identified six factors able to efficiently induce cellular senescence. Of these senescence‐inducing cytokines, the activity of five (namely IL‐1β, IL‐13, MCP‐2, MIP‐3α, and SDF‐1α) was significantly inhibited by treatment with cetuximab (an antibody targeting epidermal growth factor receptor [EGFR]), gefitinib (a small molecule inhibitor of EGFR), and EGFR knockdown. In addition, treatment with one of the senescence‐inducing cytokines, SDF‐1α, significantly increased the phosphorylation levels of EGFR, as well as Erk1/2. These results suggested that pro‐inflammatory cytokines induce cellular senescence by activating EGFR signaling. Next, we found that EGF treatment could also induce cellular senescence of IMR90 cells and HUVECs. Mechanically, EGF induced cellular senescence via excessive activation of Ras and the Ras‐BRaf‐Erk1/2 signaling axis. Moreover, EGFR activation induced IMR90 cells to secrete certain senescence‐associated secretory phenotype factors (IL‐8 and MMP‐3). In summary, we report that certain pro‐inflammatory cytokines induce cellular senescence through activation of the EGFR‐Ras signaling pathway. Our study thus offers new insight into a long‐ignored mechanism by which EGFR could regulate cellular senescence and suggests that growth signals themselves may catalyze aging under certain conditions.

中文翻译：

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表皮生长因子受体信号传导的激活介导某些促炎性细胞因子诱导的细胞衰老。

众所周知，人体内的炎症会促进机体衰老，最近的研究认为衰老细胞具有类似的作用。考虑到某些促炎细胞因子可以诱导细胞衰老，因此系统评估促炎细胞因子在细胞衰老中的作用是一个重要而紧迫的科学问题，尤其是考虑到人口老龄化的持续加剧。用促炎性细胞因子治疗IMR90细胞和HUVEC，可以识别出六种能够有效诱导细胞衰老的因子。在这些衰老诱导细胞因子中，西妥昔单抗（一种靶向表皮生长因子受体的抗体）可显着抑制五种活性（即IL-1β，IL-13，MCP-2，MIP-3α和SDF-1α）的活性。 EGFR]），吉非替尼（EGFR的小分子抑制剂），和EGFR基因敲低。此外，用一种诱导衰老的细胞因子SDF-1α处理可显着增加EGFR和Erk1 / 2的磷酸化水平。这些结果表明促炎性细胞因子通过激活EGFR信号传导诱导细胞衰老。接下来，我们发现EGF处理还可以诱导IMR90细胞和HUVEC的细胞衰老。在机械上，EGF通过过度激活Ras和Ras-BRaf-Erk1 / 2信号转导轴诱导细胞衰老。此外，EGFR激活诱导IMR90细胞分泌某些与衰老相关的分泌表型因子（IL-8和MMP-3）。总而言之，我们报道某些促炎性细胞因子通过激活EGFR-Ras信号通路来诱导细胞衰老。