Age dependence of signal transduction and cell signaling as a major factorof 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 partl y determined in rats aged 9 and 31 months (a) the concentrations and the ac tivities of signal molecules, such as G-proteins, cyclic adenosine monophos phate (cAMP) and kinases (cellular) and collagens, proteoglycans (PG) and f ibronectin (extracellular) in vivo in the skin of the back, as well as in i solated fibroblasts and keratinocytes; (b) the cell proliferation and (c) w e 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 mat rix and we compared the above mentioned parameters with those obtained by s timulation of skin cells with growth factors. There are indications that th ere 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 co ncentration and no change of the amount of fibronectin in the old rat's ski n 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 men tioned influences modulate the aging process of the skin and its cells by i ntervention into the signaling pathways, by mediating new signals to the ce lls and hence by readjusting damaged feedforward systems in the cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.