Senescent cells progressively accumulate within tissues and induce further senescence in neighboring cells through the senescence-associated secretory phenotype (SASP), thereby contributing to tissue dysfunction and aging. While senolytics selectively eliminate senescent cells, senomorphics modulate SASP without inducing cell death. Although red ginseng has been studied for anti-photoaging properties, its role in directly modulating SASP-driven keratinocyte senescence and paracrine aging signaling remains insufficiently defined. This study aimed to investigate whether Korean red ginseng-derived components (RGCs) exert senolytic or senomorphic activity in ultraviolet B (UVB)-induced senescent primary human keratinocytes. Cellular senescence was induced by repeated UVB irradiation in primary human keratinocytes. A transwell co-culture system was employed to evaluate SASP-mediated paracrine effects on neighboring keratinocytes. Three RGC fractions were examined. Senescence markers (p16 and p21), SASP factors (IL-6, IL-8, IL-1β, and TNF-α), and differentiation/proliferation markers were analyzed. Representative major ginsenosides (Rb1, Rg1, Rg3, Rc) and stress signaling pathways (MAPK/JNK and AKT) were also evaluated. RGCs did not exhibit significant senolytic activity or apoptosis induction. Instead, they demonstrated pronounced senomorphic effects by attenuating UVB-induced upregulation of p16, p21, IL-6, IL-8, and IL-1β. RGCs enhanced keratinocyte proliferation and partially restored early-to-intermediate differentiation markers. In the co-culture model, RGCs mitigated SASP-mediated paracrine effects, reducing senescence and inflammatory signaling in adjacent keratinocytes. These effects were associated with modulation of stress-responsive MAPK/JNK pathways and were partially recapitulated by ginsenosides. Our findings demonstrate that RGCs function predominantly as senomorphic modulators in UVB-induced keratinocyte senescence, attenuating SASP propagation and stress signaling without inducing cell death.
Lim et al. (Sun,) studied this question.