Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein.

中文翻译：

---

遗传毒性胁迫后循环IGFBP-4的增加及其对衰老的影响

衰老细胞分泌几种分子，统称为衰老相关的分泌表型（SASP）。在几个体外衰老后的细胞SASP中化学和物理压力，我们确定了IGFBP-4蛋白，可以将其视为一般压力介质。该因子似乎在衰老旁分泌信号传导中起关键作用。我们提供的证据表明，在用100 mGy X射线照射的小鼠以及接受计算机断层扫描的人类受试者中，遗传毒性损伤（例如低剂量照射）均可能促进血液中IGFBP-4的释放。循环中IGFBP-4水平升高可能是造成衰老的原因。我们发现，每周两次腹膜内注射IGFBP-4的小鼠在两个月内，其肺，心脏和肾脏的衰老细胞显着增加。然后，我们分析了遗传毒性应激源如何促进IGFBP-4的释放以及与该蛋白诱导衰老相关的分子途径。