WNT Signaling in Lung Aging and Disease

Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), represent a significant and increasing health burden. Current therapies are largely symptomatic, and novel therapeutic approaches are needed. Aging has emerged as a contributing factor for the development of both IPF and COPD because their prevalence increases with age, and several pathological features of these diseases resemble classical hallmarks of aging. Aging is thought to be driven in part by aberrant activity of developmental signaling pathways that thus might drive pathological changes, a process termed antagonistic pleiotropy or developmental drift. The developmental WNT pathway is fundamental for lung development, and altered WNT activity has been reported to contribute to the pathogenesis of CLD, in particular to COPD and IPF. Although to date only limited data on WNT signaling during lung aging exist, WNT signal regulation during aging and its effects on age-related pathologies in other organs have recently been investigated. In this review, we discuss evidence of dysregulated WNT signaling in CLD in the context of WNT signal alteration in organ aging and its potential impact on age-related cellular mechanisms, such as senescence or stem cell exhaustion.