The number of adults living with cystic fibrosis (CF) has already increased significantly because of drastic improvements in life expectancy attributable to advances in treatment, including the development of highly effective modulator therapy. Chronic airway inflammation in CF contributes to morbidity and mortality, and aging processes like inflammaging and cell senescence influence CF pathology. Our results show that single-cell RNA sequencing data, human primary bronchial epithelial cells from non-CF and CF donors, a CF bronchial epithelial cell line, and Cftr -knockout ( Cftr ^–/– ) rats all demonstrated increased cell senescence markers in the CF bronchial epithelium. This was associated with upregulation of fibroblast growth factor receptors (FGFRs) and mitogen-activated protein kinase (MAPK) p38. Inhibition of FGFRs, specifically FGFR4 and to some extent FGFR1, attenuated cell senescence and improved mucociliary clearance, which was associated with MAPK p38 signaling. Mucociliary dysfunction could also be improved using a combination of senolytics in a CF ex vivo model. In summary, FGFR/MAPK p38 signaling contributes to cell senescence in CF airways, which is associated with impaired mucociliary clearance. Therefore, attenuation of cell senescence in the CF airways might be a future therapeutic strategy improving mucociliary dysfunction and lung disease in an aging population with CF.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease of complex etiology. Cases of PAH that do not receive therapy after diagnosis have a low survival rate. Multiple reports have shown that idiopathic PAH, or IPAH, is associated with metabolic dysregulation including altered bioavailability of nitric oxide (NO) and dysregulated glucose metabolism. Multiple processes such as increased proliferation of pulmonary vascular cells, angiogenesis, apoptotic resistance, and vasoconstriction may be regulated by the metabolic changes demonstrated in PAH. Recent reports have underscored similarities between metabolic abnormalities in cancer and IPAH. In particular, increased glucose uptake and altered glucose utilization have been documented and have been linked to the aforementioned processes. We were the first to report a link between altered glucose metabolism and changes in glycosylation. Subsequent reports have highlighted similar findings, including a potential role for altered metabolism and aberrant glycosylation in IPAH pathogenesis. This review will detail research findings that demonstrate metabolic dysregulation in PAH with an emphasis on glycobiology. Furthermore, this report will illustrate the similarities in the pathobiology of PAH and cancer and highlight the novel findings that researchers have explored in the field.