Several studies have suggested that adiponectin is an anti-aging molecule based on its potential involvement of adipose tissue in skin aging. In this study, we investigated the anti-photoaging efficacy of an adiponectin expression-stimulating peptide derivative, pentasodium tetracarboxymethyl hexanoyl dipeptide-12 (PTHD-12), in in vitro and ex vivo human skin explant models. A double-blind, randomized, comparator placebo-controlled study was performed to confirm clinical efficacy. After irradiation with 50 mJ/cm2 of UVB, a UV-induced decrease in adiponectin expression and an increase in inflammatory cytokines in cultured human dermal fibroblasts were prevented by the PTHD-12 treatment test peptide. Mitigation of cellular senescence and senescence-associated secretory phenotype (SASP) expressions induced by UVB (50 mJ/cm2) exposure were also mitigated by the post-treatment of PTHD-12, which was also observed in an ex vivo human skin explant model. The restoration of filaggrin, loricrin, and claudin-1 protein expression in a cultured human skin explant was observed. A clinical study further confirmed that the restoration of UVB-induced skin damage, represented by increased skin redness and trans-epidermal water loss, was accelerated by the use of test peptide PTHD-12-containing products. These results suggest that targeting adiponectin may be a plausible strategy for the development of anti-aging ingredients.
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