The telomeric DNA damage response as a therapeutic target in Idiopathic Pulmonary Fibrosis

ABSTRACT: Telomere dysfunction and the telomeric DNA damage response (tDDR) correlate with aging and age-related diseases, including idiopathic pulmonary fibrosis (IPF). However, a causal role for tDDR in IPF pathogenesis has not been determined. IPF patients frequently bear germline mutations in telomerase genes, critically-short telomeres, and markers of tDDR and cellular senescence. We previously demonstrated that telomeric antisense-oligonucleotides (tASOs) targeting telomeric non-coding RNAs are selective tDDR inhibitors. Here, we employed late-generation telomerase knockout mice as a genetic model of IPF. Systemic tASOs treatment reduces DDR - including in stem/progenitor cells - inflammation, and lung fibrosis in young, adult, and in old mice. Markers of DDR correlate with lung pathology and

SUBMITTER: Francesca Rossiello 

PROVIDER: S-SCDT-10_1038-S44321-026-00500-X | biostudies-other |

REPOSITORIES: biostudies-other