In vitro studies have demonstrated that the chronological age of the donor is reflected in the behaviour of cultured skin derived cells. These differences are most striking between new-born and adult donors. but can also be detected between young adult and old adult donors, despite large inter-donor variability. This fact is important, given the justifiable concern that differences between the newborn and adults may reflect development rather than ageing.
Initial studies demonstrated that dermal fibroblasts from donors of different ages progressively lost their responsiveness to exogenous mitogens. The marked decline in growth potential of aged fibroblasts may reflect one or more of the following: a loss of high-affinity receptors to specific growth factors, as was shown for the epidermal growth factor receptor. failure of the receptor to autophosphorylate after ligand binding, although the extent to which this occurs in intact cells is unknown; or decreased capacity of post-receptor signal transduction pathways, as has been recently suggested for keratinocytes. Keratinocytes have also been found to show an age associated decrease in both mitogenic responsiveness and colony-forming potential.
Cellular release of factors capable of stimulating cells of the same type or neighbouring cells also declines with donor age. Adult donor keratinocyte cultures produced significantly (P＜0.01) less epidermal cell-derived thymocyte activating factor (similar or identical to interleukin-1β)per cell thạn newborn donor keratinocytes after confluent culture for 72 h in serum free, hormone-supplemented medium. This finding may have both immunological and proliferative implications for skin ageing. Overall, the effect of increasing donor age on response to both exogenous and endogenous mitogens is striking.
The controls for epidermal cell proliferation in vivo are largely unknown. In normal skin, however, approximately 95% of cells in the germinative basal layer do not cycle regularly, suggesting that growth inhibitors are present. An interferon-like molecule in the basal layer of the epidermis has been identified that may play a physiological role in inhibiting cellular proliferation. Preliminary data suggest that epidermal keratinocytes from adult donors are much more sensitive to the growth inhibitory effects of interferon than are keratinocytes from newborn donors. This indicates that the age-associated loss of mitogenic potential may have two separate components: decreased responsiveness to mitogens and increased responsiveness to growth inhibitors.
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