Wang Cheng, Hu Xiaoyun, Song Tianlin, Hu Fan, Du Le, Yan Chenqiong, Shen Tianwei, Li Nihong, Yang Wei, Li Li, Deng Nian, Jiang Xingwu, Wu Yelin, Ye Rui
Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
UNISKIN Research Institute on Skin Aging, Inertia Shanghai Biotechnology Co., Ltd., Shanghai, China.
J Cell Mol Med. 2025 May;29(10):e70507. doi: 10.1111/jcmm.70507.
Skin ageing accelerates systemic ageing and impairs the body's disease resistance. Inflammaging is a significant contributor to skin ageing. However, the mechanism by which inflammatory factors contribute to skin ageing remains unclear. We conducted screenings and identified CXC motif chemokine ligand 10 (CXCL10) as an inducer of skin ageing, which can be effectively inhibited by magnolin extracted from Magnolia biondii flower. Our results show that CXCL10 not only enhances beta-galactosidase (β-gal) activity but also upregulates the expression of p21/p16, along with matrix metalloproteinases (MMP1, MMP9 and MMP10), through activation of the C-X-C motif chemokine receptor 3 (CXCR3) in human primary fibroblasts. These findings suggest that CXCL10 drives skin ageing by inducing cellular senescence and extracellular matrix degradation. Importantly, treatment with magnolin significantly mitigates skin ageing phenotypes induced by CXCL10 via the p38 signalling pathway. Furthermore, our study demonstrates that magnolin significantly mitigates UV-induced skin ageing in ex vivo human skin samples as well as on human facial skin. This study provides insight into the role of chemokine CXCL10 in promoting inflammaging and proposes an innovative approach for preventing and treating skin ageing.
皮肤衰老会加速全身衰老并削弱身体的抗病能力。炎症衰老（inflammaging）是皮肤衰老的一个重要因素。然而，炎症因子导致皮肤衰老的机制仍不清楚。我们进行了筛选，并确定CXC基序趋化因子配体10（CXCL10）是皮肤衰老的诱导因子，而从望春花中提取的厚朴酚可以有效抑制它。我们的结果表明，CXCL10不仅增强β-半乳糖苷酶（β-gal）活性，还通过激活人原代成纤维细胞中的C-X-C基序趋化因子受体3（CXCR3），上调p21/p16以及基质金属蛋白酶（MMP1、MMP9和MMP10）的表达。这些发现表明，CXCL10通过诱导细胞衰老和细胞外基质降解来驱动皮肤衰老。重要的是，厚朴酚处理可通过p38信号通路显著减轻CXCL10诱导的皮肤衰老表型。此外，我们的研究表明，厚朴酚在体外人皮肤样本以及人面部皮肤上均能显著减轻紫外线诱导的皮肤衰老。这项研究深入了解了趋化因子CXCL10在促进炎症衰老中的作用，并提出了一种预防和治疗皮肤衰老的创新方法。
