Senescent fibroblast-derived growth differentiation factor 15 (GDF15) induces skin pigmentation.

Abstract Senescent fibroblasts play a role in aging pigmentation. In this study, we found that GDF15 expression levels are increased in UV-irradiated senescent fibroblasts and photoaged hyperpigmented skin. To investigate the effects of GDF15 on melanogenesis, normal human melanocytes were co-cultured with fibroblasts infected with the GDF15 lentivirus or sh-GDF15. It was found that GDF15 stimulates melanogenesis in melanocytes through MITF/tyrosinase upregulation via β-catenin signaling. The stimulatory action of GDF15 during pigmentation was further confirmed in ex vivo cultured skin and in a reconstituted human skin sample. These results suggest that senescent-fibroblast-derived GDF15 stimulates skin pigmentation and may play a role in aging-associated pigmentation.