Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence.
Nicola AlessioTiziana SquillaroGiovanni Di BernardoGiovanni GalanoRoberto De RosaMariarosa Ab MeloneGianfranco PelusoUmberto GalderisiPublished in: eLife (2020)
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.
Keyphrases
- induced apoptosis
- endothelial cells
- stress induced
- low dose
- cell cycle arrest
- dna damage
- endoplasmic reticulum stress
- randomized controlled trial
- type diabetes
- physical activity
- escherichia coli
- deep learning
- high fat diet induced
- skeletal muscle
- magnetic resonance imaging
- insulin resistance
- atrial fibrillation
- signaling pathway
- cell death
- oxidative stress
- machine learning
- binding protein
- magnetic resonance
- protein protein
- study protocol