Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32223893.
- Also identified by DOI 10.7554/eLife.54523 and PMC identifier 7136022.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Senescent cells secrete several molecules, collectively named <i>senescence-associated secretory phenotype</i> (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.
Medical subject headings
- Aging
- Cellular Senescence
- DNA Damage
- Insulin-Like Growth Factor Binding Protein 4