Royal Jelly Maintains Epidermal Stem Cell Properties by Repressing Senescence

Royal jelly (RJ), a natural product secreted by honeybees, is widely used in topical skincare products to help maintain cutaneous homeostasis. Despite its popularity, the mechanism through which RJ exerts its effects on the skin has not been fully elucidated. This study aimed to explore the impact of RJ on the proliferative ability and senescence of human primary epidermal keratinocytes (HPEKs). Our data suggested that epidermal equivalents became thicker with more p63-expressing proliferative cells upon RJ addition to the culture medium. In a two-dimensional culture system, we evaluated the effect of RJ on the proliferation of HPEKs and observed only a slight increase in cell proliferation. This suggests that RJ does not significantly enhance the proliferation of HPEKs in the short term. However, long-term culture experiments demonstrated enhanced population doubling in the RJ-treated group, indicating that RJ inhibits senescence. RJ was found to suppress cellular senescence by modulating the expression levels of ΔNp63, p16, and p21. These results were further supported by the identification of major fatty acids, such as 10-hydroxy-2-decenoic acid, in RJ. Our findings indicate that RJ can maintain epidermal stem cell properties by repressing cellular senescence, providing insights into its mechanism of action in skincare applications.