衰老
旁分泌信号
调解人
表型
细胞生物学
分泌物
生物
内科学
内分泌学
癌症研究
医学
遗传学
基因
受体
作者
Nicola Alessio,Tiziana Squillaro,Giovanni Di Bernardo,Giovanni Galano,Roberto De Rosa,Mariarosa Anna Beatrice Melone,Gianfranco Peluso,Umberto Galderisi
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2020-03-30
卷期号:9
被引量:22
摘要
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.
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