**Abstract**

Adipose-derived stem cells (ADSCs) have proven their efficiency in wound healing and skin regeneration *in vitro* and *in vivo*. They were reported to differentiate into skin cell types and migrate to wounded sites to restore cell deficiencies and functions. Secretome of ADSCs is involved in the migration and proliferation of dermal fibroblasts (DFs) and keratinocytes where growth differentiation factor 11 (GDF11) and transforming growth factor-β (TGF-β) are expected to play the principal role. Both factors are implicated in immune responses, skin cell differentiation, proliferation and pigmentation, migration and secretion of the extracellular matrix proteins. Increasing evidence has pointed the fact that ADSCs are expected to cross-react with GDF11 to ensure DF and keratinocytes proliferation to reverse the aging process. Moreover, these factors share similar intracellular mechanisms pathways that are SMAD-dependent, and target different cellular mechanisms related to regeneration or rejuvenation. This intriguing balance between GDF11 dependent aging and TGF-β-dependent regeneration still remains unclear and might be regulated in a spatio-temporal manner. Considering the clinical relevance of the mechanisms slowing or delaying the onset of age, we aimed to clarify the involvement of cell signaling pathways related to GDF11 and TGF-β in balancing cell rejuvenation and cell regeneration. Increasing the organ lifespan and functionality might be challenging issues.

**Keywords:** adipose-derived stem cells, skin, aging, regeneration, rejuvenation, wound healing, GDF11, TGF-β, SMAD pathways
