Fig. 4: Age-associated genes in the human lung interact with SARS-CoV-2 proteins.

a Venn diagram of the intersection between age-associated genes in human lung and the SARS-CoV-2: human protein interactome⁷³. Of the 14 age-associated genes that were found to also interact with SARS-CoV-2, 7 of them increased in expression with age, while 7 decreased with age. b Age-associated genes in human lung and their interaction with SARS-CoV-2 proteins, where each block contains a SARS-CoV-2 protein (underlined) and its interacting age-associated factors. Blocks are colored by the dominant directionality of the age association (orange, decreasing with age; blue, increasing with age). Gene targets with already approved drugs, investigational new drugs, or preclinical molecules are additionally denoted with an asterisk. c Tukey boxplots (interquartile range (IQR) boxes with 1.5× IQR whiskers) detailing the expression of select age-associated genes that interact with SARS-CoV-2 proteins, highlighted in (b) (n = 561 samples). Data are shown as log-transformed expression values, adjusted for sex, smoking status, and Hardy scale. The SARS-CoV-2-interacting protein is annotated in parentheses. Statistical significance of the expression variation across all age groups was assessed by a two-sided Kruskal–Wallis test on the adjusted expression values. d Heatmap showing the percentage of cells expressing each of the Age-Up genes (increasing with age) that interact with SARS-CoV-2 proteins, as highlighted in (b). Data are from the Human Lung Cell Atlas⁴⁴. e Heatmap showing the percentage of cells expressing each of the Age-Down genes (decreasing with age) that interact with SARS-CoV-2 proteins, as highlighted in (b). Data are from the Human Lung Cell Atlas⁴⁴.