A keloid is a benign fibroproliferative cutaneous disorder characterized by excessive extracellular matrix deposition, which is driven by persistent fibroblast proliferation and aberrant wound healing. Its complex pathogenesis involves genetic susceptibility, chronic inflammation, mechanical tension and dysregulated cellular signaling, resulting in poor clinical efficacy and high recurrence rates. Cellular senescence has recently become a central focus in exploring keloid pathophysiology, offering a novel perspective for elucidating its initiation, progression and recurrence. This review systematically summarizes the biological roles of cellular senescence in keloid pathology: it elaborates on the basic concepts and core molecular features of cellular senescence, details the spatial heterogeneity of senescent cell accumulation, the activation and pathological effects of senescence-associated secretory phenotype (SASP), and clarifies the molecular link between senescence-resumed proliferation (SRP) and keloid recurrence and treatment resistance. It also summarizes advances in senescence-related markers, the regulatory roles of the p53/p21 and Wnt/β-catenin pathways, and potential senescence-targeted therapies (senolytic, senomorphic, signaling intervention, cell reprogramming). Finally, we discuss the challenges and future perspectives for translating senescence research into clinical keloid treatments, aiming to provide a novel theoretical framework and therapeutic targets for keloid management.
Luo et al. (Thu,) studied this question.