At all time points c-mус mRNA was easily detectable in all cultures, with a higher level of expression in newborn and young adult keratinocytes than in keratinocytes from donors aged 40 years or older. EGFr mRNA, also well expressed prior to stimulation, was prominently induced in newborn keratinocytes following addition of growth factors (e. g..EGF), but only slightly induced in adult kerathnocytes. GADD mRNA was strongly expressed prior to stimulation in all cultures and was strongly down-regulated, more profoundly in newborn than in adult cells, within 2 h of stimulation. GADD was again maximally expressed in adult keratinocytes within 14 h after the addition of growth factors, but in newborn keratinocytes induction of GADD expression was only seen 24 h after growth factor stimulation, and the maximal mRNA level was attained only after 48 h.

The above data suggest that, at the molecular level, adult cells respond less to outside mitogenic stimuli thạn do newborn cells, as expressed by reduced mRNA levels of c-fos, c-mуc and EGFr. The reduced induction of c fos in old donor cells is of particular interest in view of the fact that proliferatively senescent WI-38 cells completely failed to express this protooncogene after serum stimulation, despite relatively intact mRNA responses for most other cell cycledependent genes. At the same time, adult keratinocytes perceived lack of growth factors before new born keratinocytes, as determined by earlier maximal induction of GADD mRNA. Taken together, these data suggest that the marked decline in growth potential of old cells is, in part, the result of their failure to generate the steady-state mRNA levels of selected genes encoding proteins essential for progression into mitosis. Photoageing differs quatitatively from intrinsic ageing at least by its different regulation of the mRNA level for c-fos which is, in turn, critical for mediating a wide variety of outside signals to responsive genes.

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