Anti-skin aging effects of Gosori liquor lees extract by regulating interactions between senescent fibroblasts and adipose-derived stem cells.

Abstract

When cellular ageing is accelerated by various extrinsic/endogenous stimuli, regenerative function deteriorates, and enriched secretomes, such as the senescence-associated secretory phenotype (SASP), contribute to chronic inflammation and cause matrix degeneration. SASPs from senescent fibroblasts exacerbate cellular senescence via autocrine signalling and also accelerate skin ageing through the induction of neighbouring cell senescence via paracrine signalling. The interaction between dermis fibroblasts and their neighbours, adipose-derived stem cells (ADSCs) in the hypodermis, which lies deep in the dermis, is a potential target for skin ageing. In this study, we observed that an extract of the lees of Gosori liquor (GLE), a traditional Korean liquor made by fermenting millet and rice, suppressed the senescence of fibroblasts, including SASP production, in a replicative senescent model. We further examined whether the anti-ageing effects of GLE on fibroblasts affected the cellular senescence of their surrounding cells, ADSCs. The results showed that senescence factors in ADSCs were suppressed by culture medium from senescent fibroblasts (SF-CM) treated with GLE compared to the SF-CM-only treated group. Furthermore, the regenerative ability of ADSCs was promoted in the GLE-treated SF-CM group. ADSC migration was stimulated by upregulating the levels of α-smooth muscle actin, collagen type I alpha 2, and vascular endothelial growth factor expression through the PI3K/AKT pathway. Those results indicate that GLE can exert regenerative ability by regulating fibroblasts, and adipocyte interactions, improving cellular senescence. We conducted a clinical trial of subjects over 45 years of age to confirm the anti-ageing effects of GLE in vivo and observed changes in ageing parameters, such as skin wrinkles and volume on the face (IRB No. DM-IRB-2023-809-01-T1). The results showed that GLE-containing cream was more effective in improving skin wrinkles, elasticity, density, thickness, and volume around sunken eyes after 4 weeks of use than placebo. In conclusion, GLE plays an important role in inhibiting the ageing transition to ADSCs by inhibiting the senescence of fibroblasts and can be a promising anti-ageing strategy.