**5.3 Melanocytes regulation**

ADSCs also interplay with the activation loop of melanocytes by modulating enzyme-producing melanin activity. ADSCs by increasing their TGF-β secretion induced melanocytes to downregulate the expression of melanogenic enzymes and prevent site-specific pigmentation in reconstructed skin grafts. These interactions might be of interest in clinical applications by modulating melanin synthesis and impacting whitening of the skin through TGF-β [100]. DF increased TGF-β secretion, thus maintaining melanocytes in an immature state, and acted on melanocytes to modulate melanin-producing enzymes and thus skin pigmentation [101], suggesting that dermal composition in cells might determine the production of mature melanocytes and hence melanin transfer to keratinocytes. However, a recent study has shown that rGDF11 significantly reduced melanin production in melanocytes and 3D skin equivalents [24]. On the other hand, during aging, ROS accumulation by cell proliferation was reported as the initiator of the occurrence of vitiligo and its progression [102].

These reports might increase our thought on a potential ratio of GDF11 and TGF-β in different skin type and color. This ratio could result on a balance between skin pigmentation and skin yought and lead to a sustainable skin biology and function through regulation of the mechanisms related to skin cell proliferation and rejuvenation. If this is the case, one should conclude that white skins should present higher amounts of GDF11 and youthful aspects and present less symptoms of cell apoptosis and senescence during cell life. These observations must draw more attention in the future to better understand the paradigms triggering the mechanisms related to skin aging and pigmentation.
