Accumulation of senescent cells promotes the development of age-related pathologies and deterioration. In human skin, senescent cells potentially impair structure and function by secreting a mixture of signaling molecules and proteases that influence neighboring cells and degrade extracellular matrix components, such as elastin and collagen. One of the key underlying mechanisms of senescence and extrinsic skin aging is the increase of intracellular reactive oxygen species and resulting oxidative stress. Tert-butyl hydroperoxide (tBHP) is a known inducer of oxidative stress and cellular damage, acting at least in part by depleting the antioxidant glutathione. Here, we provide a detailed characterization of tBHP-induced senescence in human dermal fibroblasts in monolayer culture. In addition, results obtained with more physiological experimental models revealed that tBHP treated 3D reconstructed skin and ex vivo skin developed signs of chronic tissue damage, displaying reduced epidermal thickness and collagen fiber thinning. We, therefore, propose that tBHP treatment can be used as a model to study the effects of extrinsic skin aging, focusing mainly on the influence of environmental pollution.

衰老细胞的积累促进了与年龄相关的病理和恶化的发展。在人类皮肤中，衰老细胞可能通过分泌信号分子和蛋白酶的混合物来影响结构和功能，这些信号分子和蛋白酶会影响邻近细胞并降解细胞外基质成分，例如弹性蛋白和胶原蛋白。衰老和外在皮肤老化的关键潜在机制之一是细胞内活性氧的增加和由此产生的氧化应激。叔丁基氢过氧化物 (tBHP) 是一种已知的氧化应激和细胞损伤诱导剂，至少部分通过消耗抗氧化剂谷胱甘肽起作用。在这里，我们提供了单层培养中人真皮成纤维细胞中 tBHP 诱导的衰老的详细表征。此外，离体皮肤出现慢性组织损伤的迹象，表现出表皮厚度减少和胶原纤维变细。因此，我们建议 tBHP 治疗可以作为研究外在皮肤老化影响的模型，主要关注环境污染的影响。