Longevity & AgingCellular Senescence Drives Crohn's Intestinal Fibrosis Through a Double-Edged Mechanism
This 2026 review in Frontiers in Immunology systematically examines how cellular senescence shapes intestinal fibrosis in Crohn's disease (CD). The authors describe four key triggers of senescence in the CD microenvironment—oxidative stress, telomere dysfunction, endoplasmic reticulum stress, and genotoxic damage—and analyze how each major intestinal cell type (fibroblasts, myofibroblasts, endothelial, epithelial, and immune cells) contributes to fibrotic progression when senescent. Central to this process is the senescence-associated secretory phenotype (SASP), which drives paracrine inflammation, ECM imbalance, and stem cell dysfunction. Crucially, acute senescence can limit fibrosis and aid wound healing, while chronic senescence sustains destructive inflammation. The review concludes by evaluating senolytic and senomorphic therapies as promising antifibrotic strategies for CD patients.
