Fibrosis

Fibrosis is the pathological excess deposition of extracellular matrix — predominantly fibrillar collagens type I and III — by activated myofibroblasts in response to chronic injury, inflammation, or senescent-cell SASP signalling, replacing normal parenchymal cells with a stiff, poorly vascularised scar. TGF-beta1 is the dominant pro-fibrotic cytokine, signalling through SMAD2/3 to transcriptionally activate collagen synthesis, suppress MMPs, and drive fibroblast-to-myofibroblast differentiation; IL-11, PDGF, and connective tissue growth factor (CTGF/CCN2) cooperate in a context-dependent manner. Age markedly increases fibrotic susceptibility because impaired senescent cell clearance sustains TGF-beta and SASP output, macrophage polarisation shifts toward pro-fibrotic M2 phenotypes, and regenerative responses become dysregulated, making liver cirrhosis, idiopathic pulmonary fibrosis, and cardiac fibrosis major determinants of age-related organ failure.