**8. The spatio-temporal role of the TFG-β pathway in relationship with GDF11 in skin aging**

When stimulating ADSCs through binding to their specific receptor membrane, activin type IIB (ActIIBR), GDF11 activates the SMAD2/3 pathways. Similar mechanism might be achieved on ADSCs by TGF-β, suggesting that interference with TGF-β and GDF11 mechanisms might be the key regulator of healing and aging. The same activated SMAD mechanisms pathway did not achieve similar biological activity and targeted probably different intracellular and intranuclear effectors. These considerations might suggest that even different specific receptors are involved in the extracellular interactions of these factors, a competitive attractivity might be observed between their intracellular effectors, which are the SMAD 2/3 proteins. When the factors compete for these proteins, one can speculate that the favored pathway would be associated either to the amount of the activated receptor (TGF-β or GDF11) or to the sensibility of these receptors to their respective ligands.

Another point of view that could be important to mention is the variation in secretion level of these factors during aging. At this fact, serum level of GDF11 has been reported to decrease during age while TGF-β variation was not really investigated. The antiaging pathway GDF11-dependent could be replaced progressively during aging by the TGF-β regenerating one. This might favor tissue regeneration and repair rather than rejuvenation, leading to the appearance of the symptoms of age.

Thus complicating the dilemma between rejuvenation and regeneration. Secretome composition of ADSCs might be impacted by the aging process or the different epigenetic factors.
