Royal jelly suppresses senescence-associated secretory phenotype in senescent human epidermal keratinocytes

BACKGROUND: Royal Jelly (RJ) is widely used in cosmetics for its beneficial skin effects, but its impact on cellular senescence remains unclear. Senomorphic agents that suppress the senescence-associated secretory phenotype (SASP) offer safe therapeutic strategies for skin aging. This study investigates the senomorphic effects of RJ on epidermal senescence. METHODS AND RESULTS: We utilized an in vitro replicative senescence model of normal human epidermal keratinocytes, validating our findings with cells from chronologically aged adult donors, including a 75-year-old. Results demonstrated that RJ significantly suppresses multiple SASP factors, including interleukin (IL)-6 and C-X-C motif ligand (CXCL) family members, in both models without inducing cytotoxicity. Mechanistically, RNA-sequencing revealed that senescence upregulated pro-inflammatory factors via TNF-α and NF-κB signaling pathways. RJ acts as a multitarget senomorphic agent, inhibiting these senescence-activated pathways and reducing oxidative stress. CONCLUSIONS: RJ is a potent natural senomorphic agent capable of modulating complex SASP networks. It provides valuable insights into potential strategies for mitigating skin inflammation and preserving youthfulness.