Cellular senescence mediates fibrotic pulmonary disease

• DOI: 10.1038/ncomms14532
• Publication Date: 2017-02-23T10:10:56Z
• Authors: Marissa J. Schafer; Thomas A. White; Koji Iijima; Andrew J. Haak; Giovanni Ligresti; Elizabeth J. Atki...; Ann L. Oberg; Jodie Birch; Hanna Salmonowicz; Yi Zhu; Daniel L. Mazula; Robert W. Brooks; Heike Fuhrmann-St...; Tamar Pirtskhalava; Y. S. Prakash; Tamara Tchkonia; Paul D. Robbins; Marie Christine A...; João F. Passos; James L. Kirkland; Daniel J. Tschump...; Hirohito Kita; Nathan K. LeBrasseur
• Keywords: Senescence

Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF tissue and senescent cell deletion rejuvenates health in aged mice. Whether how cells regulate or if their removal may be an efficacious intervention strategy unknown. Here we demonstrate elevated abundance of biomarkers lung, with p16 expression increasing severity. We show that the secretome fibroblasts, which selectively killed senolytic cocktail, dasatinib plus quercetin (DQ), fibrogenic. Leveraging bleomycin-injury model, early-intervention suicide-gene-mediated ablation improves function physical health, although visibly unaltered. DQ treatment replicates benefits transgenic clearance. Thus, our findings establish fibrotic mediated, part, cells, can targeted improve