Cellular senescence limits acute lung injury induced by mechanical ventilation

Jorge Blazquez-Prieto; Covadonga Huidobro; Ines Lopez-Alonso; Laura Amado-Rodriguez; Paula Martin-Vicente; Cecilia Lopez-Martinez; Irene Crespo; Cristina Pantoja; Pablo J Fernandez-Marcos; Manuel Serrano; Jacob I Sznajder; Guillermo M Albaiceta

We provide new evidence that acute lung injury and its treatment with mechanical ventilation cause senescence of the alveolar epithelium, Addition of mechanical stretch to a previous injured lung alters the nuclear envelope and causes DNA damage, triggering a senescent-like response with presence of SHF and activation of the p53/p21 pathway. Absence of p21 worsens lung injury by increasing cell apoptosis; however, blockade of Lamin-A scaffolding using HIV protease inhibitors . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.005983 doi: bioRxiv preprint 16 ameliorates the stretch-induced chromatin changes and increases a senescent response, decreasing the severity of lung injury. Figure 7 summarizes the proposed mechanisms. Collectively, these findings suggest that senescence is a short-term homeostatic mechanism to ameliorate massive damage induced by the addition of acid aspiration with mechanical stretch.