Cellular Senescence Drives Fibrotic Pulmonary Disease
Year: 2017
Type: conference-abstract
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease characterized by interstitial remodeling, leading to severely compromised lung structure and function. Cellular senescence, a stress-induced state of replicative arrest, is causally implicated in numerous age-related diseases. Markers of senescence are detectable within parenchyma of chronologically aged and IPF lung tissue. Whether and how senescent cells mechanistically regulate IPF or if their removal may be an efficacious intervention strategy is unknown. Through examination of IPF tissue and transcriptome datasets, we discovered elevated abundance of senescence effectors and senescence associated secretory phenotype (SASP) factors, with select markers increasing concordantly with disease severity. Leveraging intratracheal administration of bleomycin to replicate aspects of IPF, we demonstrate that suicide gene-mediated ablation of p16Ink4a-expressing senescent cells in Ink-Attac mice improves pulmonary function, body composition, and physical performance. Senolytic DQ treatment replicates several benefits of transgenic clearance. Thus, our findings demonstrate for the first time that fibrotic pulmonary disease is mediated in part by senescent cells, which can be pharmacologically targeted to improve physical health and function.
Source: Innovation in Aging
Institutions: Mayo Clinic, Newcastle University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,977
OpenAlex ID: W2730855415