As one of the earliest and most visible phenomenon of aging, gray hair makes it a unique model system for investigating the mechanism of aging. Ionizing radiation successfully induces gray hair in mice, and also provides a venue to establish an organ-cultured human gray hair model. To establish a suitable organ-cultured human gray HF model by IR, which imitates gray hair in the elderly, and to explore the mechanisms behind the model. By detecting growth parameters, melanotic and senescence markers of the model, we found that the model of 5 Gy accords best with features of elderly gray hair. Then, we investigated the formation mechanisms of the model by RNA-sequencing. We demonstrated that the model of organ-cultured gray HFs after 5 Gy irradiation is closest to the older gray HFs. Moreover, the 5 Gy inhibited the expression of TRP-1, Tyr, Pmel17, and MITF in hair bulbs/ORS of HFs. The 5 Gy also significantly induced ectopically pigmented melanocytes and increased the expression of DNA damage and senescence in HFs. Finally, RNA-seq analysis of the model suggested that IR resulted in cell DNA damage, and the accumulation of oxidative stress in the keratinocytes. Oxidative stress and DNA damage caused cell dysfunction and decreased melanin synthesis in the gray HFs. We found that HFs irradiated at 5 Gy successfully constructed an appropriate aging HF model. This may provide a useful model for cost-effective and predictable treatment strategies to human hair graying and the process of aging.

作为最早和最明显的衰老现象之一，白发使其成为研究衰老机制的独特模型系统。电离辐射成功诱导小鼠白发，也为建立器官培养的人类白发模型提供了场所。通过 IR 建立合适的器官培养的人类灰色 HF 模型，模拟老年人的白发，并探索模型背后的机制。通过检测模型的生长参数、黑色素和衰老标志物，我们发现5 Gy的模型最符合老年白发的特征。然后，我们通过 RNA 测序研究了模型的形成机制。我们证明了 5 Gy 照射后器官培养的灰色 HFs 模型最接近较旧的灰色 HFs。此外，5 Gy 抑制了 TRP-1、Tyr、Pmel17、和毛球中的 MITF/HF 的 ORS。5 Gy 还显着诱导了异位色素沉着的黑素细胞，并增加了 HFs 中 DNA 损伤和衰老的表达。最后，模型的 RNA-seq 分析表明，IR 导致细胞 DNA 损伤，以及角质形成细胞中氧化应激的积累。氧化应激和 DNA 损伤导致灰色 HFs 中的细胞功能障碍和黑色素合成减少。我们发现在 5 Gy 下辐照的 HFs 成功地构建了一个合适的老化 HF 模型。这可能为人类头发变白和衰老过程提供具有成本效益和可预测的治疗策略的有用模型。模型的 RNA-seq 分析表明，IR 导致细胞 DNA 损伤，以及角质形成细胞中氧化应激的积累。氧化应激和 DNA 损伤导致灰色 HFs 中的细胞功能障碍和黑色素合成减少。我们发现在 5 Gy 下辐照的 HFs 成功地构建了一个合适的老化 HF 模型。这可能为人类头发变白和衰老过程提供具有成本效益和可预测的治疗策略的有用模型。模型的 RNA-seq 分析表明，IR 导致细胞 DNA 损伤，以及角质形成细胞中氧化应激的积累。氧化应激和 DNA 损伤导致灰色 HFs 中的细胞功能障碍和黑色素合成减少。我们发现在 5 Gy 下辐照的 HFs 成功地构建了一个合适的老化 HF 模型。这可能为人类头发变白和衰老过程提供具有成本效益和可预测的治疗策略的有用模型。