IGFBP5 is released by senescent cells and is internalized by healthy cells, promoting their senescence through interaction with retinoic receptors

• DOI: 10.1186/s12964-024-01469-1
• Publication Date: 2024-02-13T09:02:31Z
• Authors: Nicola Alessio; Domenico Aprile; Gianfranco Peluso; Valeria Mazzone; Deanira Patrone; Giovanni Di Bernardo; Umberto Galderisi
• Keywords: Senescence

Abstract Cells that are exposed to harmful genetic damage, either from internal or external sources, may undergo senescence if they unable repair their DNA. Senescence, characterized by a state of irreversible growth arrest, can spread neighboring cells through process known as the senescence-associated secretory phenotype (SASP). This phenomenon contributes both aging and development cancer. The SASP comprises variety factors regulate numerous functions, including induction secondary senescence, modulation immune system activity, remodeling extracellular matrix, alteration tissue structure, promotion cancer progression. Identifying key within is crucial for understanding underlying mechanisms developing effective strategies counteract cellular senescence. Our research has specifically focused on investigating role IGFBP5, component observed in various experimental models conditions. Through our studies, we have demonstrated IGFBP5 actively promoting induce cells. We gained valuable insights into which exerts its pro-senescence effects. These include release following genotoxic stress, involvement signaling pathways mediated reactive oxygen species prostaglandins, internalization via specialized structures called caveolae, interaction with specific protein RARα. By uncovering these mechanisms, advanced intricate process. significance pro-aging factor stems an vivo study conducted patients undergoing Computer Tomography analysis. In patients, elevation circulating levels response radiation-induced organismal stress. Globally, findings highlight potential promising therapeutic target age-related diseases