Fig. 2: Lung cellular senescence increases with aging.
From: Molecular programs of fibrotic change in aging human lung
a p16 expression by age in the LAC (log scale). Pearson R is shown. The gray band represents the 95% confidence interval. b Gene set enrichment analysis of 11 consensus senescence markers from DePianto et al15. Genes were ranked by Pearson R between normalized gene expression and age. Normalized enrichment score, P value, and adjusted P value are shown. Single sample gene set enrichment analysis using the 11-gene signature is shown for individuals in the LAC (N = 17 biologically independent samples in each group) and GTEx lung (N = 69 biologically independent samples in each group). P values are for the two-sided Student’s t-test. For the boxplots, the middle line shows the median, the lower and upper hinges are the first and third quartiles, and the lower and upper whiskers extend to the value at most 1.5 IQR below the first quartile or 1.5 IQR above the third quartile, respectively. Data beyond the end of the whiskers are outlying points. c Ingenuity pathway analysis (IPA) computed with the genes from LAC that were correlated with age at p ≤ 0.05 level of significance. P values are for right-tailed Fisher’s exact test without adjustment for multiple comparisons. d qPCR-quantified telomere length plotted by age for the LAC (N = 84 biologically independent samples). Pearson R is shown. The gray band represents the 95% confidence interval. The circled subsamples differ in telomere length (1 = long, 2 = short) and were used for γH2AX immunohistochemistry, with representative images below (Scale bars: 25 µm) and quantification to the right (N = 3 samples in each group, N = 15 images examined per sample). Each point represents the number of γH2AX+ cells within a separate image. P value is for a two-sided Welch’s t-test comparing all values for the long telomere group versus the short. Data were presented as mean values ± SEM. Differential gene expression of the subsamples by bulk RNA-seq was used for IPA. The predicted activity of upstream senescence regulators in the short telomere subgroup, with Z-scores and P values, is shown in the table.
