Age dependence of signal transduction and cell signaling as a major factor of intervention into the aging process.

Nowadays, it has become necessary to investigate the mechanisms underlying aging changes and their modulation. Of particular interest are the cellular and molecular level cell-cell and cell-matrix interactions. Thus, we partly determined in rats aged 9 and 31 months (a) the concentrations and the activities of signal molecules, such as G-proteins, cyclic adenosine monophosphate (cAMP) and kinases (cellular) and collagens, proteoglycans (PG) and fibronectin (extracellular) in vivo in the skin of the back, as well as in isolated fibroblasts and keratinocytes; (b) the cell proliferation and (c) we tried to retard the aging process in the skin by topical application (or by addition to cell cultures) of fetal mesenchymal cells, PGs, and soya matrix and we compared the above mentioned parameters with those obtained by stimulation of skin cells with growth factors. There are indications that there is (a) no change in the quantity of Gs-proteins but a reduction of the binding capacity. We found lower concentrations of cAMP, a reduced activity of protein kinase C in vivo, a higher collagen crosslinking, a lower PG concentration and no change of the amount of fibronectin in the old rat's skin and (b) there is a more or less extensive restoration of these parameters by all the above mentioned stimuli. So, we conclude that all the above mentioned influences modulate the aging process of the skin and its cells by intervention into the signaling pathways, by mediating new signals to the cells and hence by readjusting damaged feedforward systems in the cells.