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eLife Volume 9 ,2020-03-29
Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence
Human Biology and Medicine
Nicola Alessio 1 Tiziana Squillaro 1 Giovanni Di Bernardo 2 Giovanni Galano 2 Roberto De Rosa 2 Mariarosa AB Melone 3 Gianfranco Peluso 4 Umberto Galderisi 1 , 4 , 5
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Received 2019-12-17, accepted for publication 2020-03-29, Published 2020-03-29

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.


Mouse;Human;secretome;SASP;senescence;paracrine signaling;mesenchymal stromal cells


© 2020, Alessio et al
http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.


Nicola Alessio,Tiziana Squillaro,Giovanni Di Bernardo,Giovanni Galano,Roberto De Rosa,Mariarosa AB Melone,Gianfranco Peluso,Umberto Galderisi. Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence. eLife ,Vol.9(2020)



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