Fig. 11

Age-dependent regulation of marker genes of pulmonary resident cells. We retrieved marker genes from various databases and list individual genes in supplementary Table S12. The data are enrichment scores based on signal intensities of individual genes and infer a change in cellular activity with age. For each cell type, we compute the enrichment score on a large set of genes (range 44–434 genes for the mouse and 147–922 genes for human pulmonary cells; supplementary Table S12). A Anatomical location of pulmonary cells in lung. B Depicted are violin plots of age regulated enrichment scores for 9 different pulmonary cells of the mouse. Panel C1: Depicted are violin plots of age regulated enrichment scores for 9 different pulmonary cells of the human test set. Panel C2: Depicted are violin plots of age regulated enrichment scores for 9 different pulmonary cells of the human validation set. Statistical significance testing: “Kruskal–Wallis” test. ns: not significant, *p < 0.05, **p < 0.01, ***p < 0.001. D Scheme of alveoli and the interplay of AT2 surfactant producing cells with alveolar macrophages. Alveolar type 2 cells produce surfactant. We show gene regulations in the aged lung of mice, which code for the main biosynthetic pathway of phosphatidylcholine, i.e., α-isoform of choline kinase (CK), choline-phosphate cytidylyltransferase (PCYT1A/CCTα) and choline phosphotransferase (CHPT1/CPT1). These genes code for main biosynthetic pathway of phosphatidylcholine, and the results imply an age-related change in the production and composition of surfactant phospholipids. Additionally, phosphatide phosphohydrolase (PAP) catalyzes the conversion of phosphatidic acid (PA) to diacylglycerol (DAG), and we observed its age-related down-regulation. Furthermore, diacylglycerol kinase (DGK) catalyzes the phosphorylation of diacylglycerol to PA and DGK expression is repressed. Through replacement of choline from phosphatidylcholine (PC) or the replacement of an ethanolamine group from phosphoethanolamine (PE) the enzymes phosphatidylserine synthase PSS1 and PSS2 catalyze the synthesis of phosphatidylserine (PS). Furthermore, phosphatidylethanolamine N-methyltransferase (PEMT) produces PC via methylation of PE, and in the lung of aged mice Pss1/2 and Pemt are upregulated. Finally, ATP binding cassette subfamily A member 3 (Abca3) is essential for the transport of lamellar body to the plasma membrane, and annexin A7 (Anxa7) supports the fusion with the plasma membrane and its secretion into alveolar fluid while phospholipase A2 isoform 5 (Pla2g5) hydrolyses surfactant phospholipids and stimulates the production of inflammatory lipids. In the aged lung, we found Abca3 repressed and Anxa7 and Pla2g5 upregulated