Modeling human gray hair by irradiation as a valuable tool to study aspects of tissue aging

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.