Abstract
Epidermal thinning refers to the thinning of the entire epidermis with age. It is thought that a decline in the epidermal stem cells leads to epidermal thinning with age, but the mechanism has not been elucidated yet. To elucidate the mechanism of epidermal thinning with age, we focused on epidermal stem cells and their environment. Epidermal stem cells are maintained near the basement membrane, and the oxygen concentration of their environment is lower than the normal oxygen concentration. It is known that a transcription factor called hypoxia inducible factor-1α (HIF-1α) is active in cells in a low oxygen environment. Comparison of the transcriptional activity of HIF-1α by culture of normal human epidermal keratinocytes (NHEKs) in normoxia and hypoxia confirmed that cells cultivated in hypoxia had high HIF-1α transcription activity. Moreover, it was also confirmed that the expression level of melanoma- associated chondroitin sulfate proteoglycan (MCSP), a stem cell marker, was high in hypoxia. Next, we performed a similar test with neonatal-derived and aged-derived epidermal cells, and we confirmed that the HIF-1α transcriptional activity and MCSP synthesis rate were reduced. Based on this, we inferred that HIF-1α transcriptional activity decreases with age and that epidermal stem cells tend to differentiate, the supply of epidermal cells decreases, and the epidermis thins with age. Furthermore, we found that red clover flower extract promotes HIF-1α transcriptional activity and the MCSP synthesis rate. We also analyzed the mechanism by which red clover flower extract promotes HIF-1α transcriptional activity, and we confirmed that the mechanism of HIF-1α was different from that of cobalt chloride, which has a transcriptional activation effect. Moreover, a cream containing red clover flower extract improved the epidermis thickness of the skin within 2 months and increased the stratum corneum water content.
