Aryl hydrocarbon receptor: From pathogenesis to therapeutic targets in aging-related tissue fibrosis

Aging promotes chronic inflammation, which contributes to fibrosis and decreases organ function. Fibrosis, the excessive synthesis and deposition of extracellular matrix components, is the main cause of most chronic diseases including aging-related organ failure. Organ fibrosis in the heart, liver, and kidneys is the final manifestation of many chronic diseases. The aryl hydrocarbon receptor (AHR) is a cytoplasmic receptor and highly conserved transcription factor that is activated by a variety of small-molecule ligands to affect a wide array of tissue homeostasis functions. In recent years, mounting evidence has revealed that AHR plays an important role in multi-organ fibrosis initiation, progression, and therapy. In this review, we summarise the relationship between AHR and the pathogenesis of aging-related tissue fibrosis, and further discuss how AHR modulates tissue fibrosis by regulating transforming growth factor-β signalling, immune response, and mitochondrial function, which may offer novel targets for the prevention and treatment of this condition.