The effect of aging in primary human dermal fibroblasts

Skin aging is a complex process, and alterations in human skin due to aging have distinct characteristic as compared to other organs. The aging of dermal cells and the biological mechanisms involved in this process are key areas to understand skin aging. A large number of biological mechanisms, such as decreasing of protein synthesis of extracellular matrix or increasing of degradation, are known to be altered through skin aging. However, environmental influence can accelerate this characteristic phenotype. In this study, we analyzed primary human dermal fibroblasts in three different in-vitro aging models—UVB irradiation and accelerated proliferation of human dermal fibroblasts from young donors as well as from elderly donors—for the gene expression of COL1A1, COL1A2, COL3A1, COL4A1, COL7A1, MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, MMP13, MMP14, TIMP1, TIMP2, TIMP3, TIMP4, IL1B, IL1A, IL6, IL8, IL10, PTGS2, TP53, CASP3, LMNA, SIRT1. We compared the gene expression levels with young control. Furthermore, the behavior of skin fibroblasts was also evaluated using cell growth rate. The findings reveal that the gene expression levels in skin fibroblasts was altered in the process of aging in all three in-vitro aging models, and the cell growth rate was reduced, suggesting that these methods can be employed to understand skin aging mechanisms as well as drug discovery screening method.

皮肤衰老是一个复杂的生物学过程，相较于其他人体器官，衰老引发的人类皮肤改变具有独特的特征。真皮细胞的衰老及其相关的生物学调控机制，是解析皮肤衰老本质的核心研究方向。已知在皮肤衰老过程中，大量生物学机制发生异常改变，例如细胞外基质（extracellular matrix）的蛋白质合成能力下降、降解过程异常增强。然而，外界环境影响可加速这一特征性表型（phenotype）的出现。
本研究针对三种不同的体外衰老模型中的原代人真皮成纤维细胞（primary human dermal fibroblasts）展开分析，分别为紫外线B（UVB）照射模型、年轻供体来源的人真皮成纤维细胞加速增殖模型，以及老年供体来源的人真皮成纤维细胞模型；检测的基因表达靶点包括COL1A1、COL1A2、COL3A1、COL4A1、COL7A1、MMP1、MMP2、MMP3、MMP7、MMP8、MMP9、MMP10、MMP12、MMP13、MMP14、TIMP1、TIMP2、TIMP3、TIMP4、IL1B、IL1A、IL6、IL8、IL10、PTGS2、TP53、CASP3、LMNA、SIRT1。本研究以年轻供体来源的成纤维细胞作为对照，对比各组的基因表达水平。此外，本研究还通过检测细胞生长速率，评估皮肤成纤维细胞的增殖行为。
研究结果显示，在三种体外衰老模型中，皮肤成纤维细胞的基因表达水平均随衰老过程发生改变，且细胞生长速率显著降低；这表明上述模型既可用于解析皮肤衰老的生物学机制，也可作为药物发现的体外筛选模型。