(a) Transcriptional changes corresponding to senescence effectors (black), SASP growth factors (dark grey) and SASP matrix remodelling (light grey) genes that were identified in independent RNAseq (control n=19, IPF n=20) and microarray human lung IPF versus control data sets are shown. IPF samples analysed by microarray were severity classified by FVC as low (≥80%; n=17), moderate (50–80%; n=60) or severe (<50%; n=16) and compared with control (n=64) (q<0.05 for both RNAseq and microarray). Human lung tissue sections were IHC stained for p16 in b control and (c,d) IPF lung samples with (c) fibroblastic foci and (d) honeycomb lung depicted. p16-positive fibroblasts (stars) and epithelial cells (arrows) are indicated ( × 200 images). (e) Control (left panel) and IPF (right panel) lung sections were analysed for frequencies of DNA damage foci (γH2A.X, green) and telomere immuno-fluorescence in situ hybridization (red) within alveolar compartments. Arrows indicate γH2A.X foci co-localizing with telomeres (TAF) (scale bar, 5 μm), shown at higher magnification on the right (images are from maximum intensity projection). (f) Mean number of γH2A.X foci (left) and percentage of cells containing at least one TAF (right) were determined through quantification of Z-stack images with at least 100 cells per sample ( × 100 images) (mean±s.e.m.; control n=10 (grey), IPF n=27 (red); t-test *P≤0.05).