Fibroblasts, critical for skin structure and function via extracellular matrix (ECM) production, undergo senescence linked to ECM changes and inflammation via senescence-associated secretory phenotypes (SASPs). Transforming growth factor (TGF-β), a pleiotropic cytokine, modulates fibroblast function through multiple signaling pathways, inducing cell cycle arrest, oxidative stress, DNA damage, and SASP production. These processes disrupt ECM homeostasis, exacerbate inflammation, and impair tissue repair, contributing to pathological skin changes. TGF-β induced fibroblast senescence involves multiple mechanisms and pathways. It causes cell cycle arrest by upregulating CDK inhibitors and activating the p53 pathway. TGF-β also promotes oxidative stress-induced senescence by increasing reactive oxygen species (ROS) production, activating pathways like SMAD, and causing DNA damage. In photoaging, UV exposure induces fibroblast senescence via TGF-β related mechanisms, reducing collagen production and increasing MMP levels. TGF-β also suppresses immune cell functions, creating an immunosuppressive microenvironment that accelerates cellular senescence. In refractory skin diseases like vitiligo, melanoma, and so on, TGF-β plays a complex role. Its abnormal activation drives fibroblast senescence, impacting immune responses and skin structure. However, Maintaining the normal expression of TGF-β preserves ECM homeostasis, promotes collagen synthesis, and reduces inflammatory factor expression. Emerging therapeutic strategies targeting TGF-β signaling show promise. Pharmaceutical agents and phototherapy mitigate senescence by modulating TGF-β pathways and thus suppress ROS, enhancing collagen synthesis. Combined approaches synergistically improve skin repair and elasticity. In summary, TGF-β significantly regulates fibroblast senescence in refractory skin diseases through various mechanisms and pathways. Its precise modulation could enhance skin repair and anti-aging therapies. However, further research is needed to explore the interactions between anti-aging ingredients and their clinical effects.
