Zheng Yujie, Lei Jindi, Zhang An, Cao Cheng, Xu Aie, Zhou Miaoni, Lin Fuquan
Hangzhou Third People's Hospital affiliated to the Zhejiang Chinese Medical University, 38 Xihu Rd, Hangzhou, 310009, Zhejiang, China.
Department of Dermatology, Hangzhou Third People's Hospital, Affiliated Hangzhou Dermatology Hospital, 38 Xihu Rd, Hangzhou 310009, Zhejiang, China.
Exp Gerontol. 2025 Nov;211:112900. doi: 10.1016/j.exger.2025.112900. Epub 2025 Sep 25.
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.
成纤维细胞通过产生细胞外基质（ECM）对皮肤结构和功能至关重要，它会通过衰老相关分泌表型（SASP）经历与ECM变化和炎症相关的衰老。转化生长因子（TGF-β）是一种多效性细胞因子，通过多种信号通路调节成纤维细胞功能，诱导细胞周期停滞、氧化应激、DNA损伤和SASP产生。这些过程破坏ECM稳态，加剧炎症并损害组织修复，导致皮肤病理变化。TGF-β诱导的成纤维细胞衰老涉及多种机制和途径。它通过上调细胞周期蛋白依赖性激酶（CDK）抑制剂并激活p53途径来导致细胞周期停滞。TGF-β还通过增加活性氧（ROS）的产生、激活SMAD等途径并引起DNA损伤，促进氧化应激诱导的衰老。在光老化中，紫外线照射通过TGF-β相关机制诱导成纤维细胞衰老，减少胶原蛋白产生并增加基质金属蛋白酶（MMP）水平。TGF-β还抑制免疫细胞功能，营造一个加速细胞衰老的免疫抑制微环境。在白癜风、黑色素瘤等难治性皮肤病中，TGF-β发挥着复杂的作用。其异常激活驱动成纤维细胞衰老，影响免疫反应和皮肤结构。然而，维持TGF-β的正常表达可保持ECM稳态，促进胶原蛋白合成并降低炎症因子表达。针对TGF-β信号传导的新兴治疗策略显示出前景。药物制剂和光疗通过调节TGF-β途径减轻衰老，从而抑制ROS，增强胶原蛋白合成。联合方法可协同改善皮肤修复和弹性。总之，TGF-β通过各种机制和途径显著调节难治性皮肤病中的成纤维细胞衰老。其精确调节可增强皮肤修复和抗衰老治疗。然而，需要进一步研究来探索抗衰老成分之间的相互作用及其临床效果。
