REGULATIONS OF COLLAGEN-SYNTHESIS BY ASCORBIC-ACID, TRANSFORMING GROWTH-FACTOR-BETA AND INTERFERON-GAMMA IN HUMAN DERMAL FIBROBLASTS CULTURED IN 3-DIMENSIONAL COLLAGEN GEL ARE PHOTOAGING-INDEPENDENT AND AGING-INDEPENDENT

Decreased collagen synthesis and loss of responsiveness to growth fact ors are well known phenomena in in vivo or in vitro aged cells, Ascorb ic acid and some cytokines such as transforming growth factor-beta and interferon-gamma are important regulators of collagen synthesis. To i nvestigate the responsiveness of fibroblasts with regard to the photoa ging and aging process, we examined the effect of ascorbic acid, TGF-b eta, and IFN-gamma on collagen synthesis in dermal fibroblasts from th ree newborn foreskins (1 day old) and in both exposed and unexposed sk in fibroblasts from 4 old individuals (60-76 years old) cultured in mo nolayer and in collagen gel. Nt demonstrated that basal levels of coll agen synthesis decreased with increasing age. Photoaged fibroblasts in collagen gel showed greater basal collagen synthesis than aged fibrob lasts in the same individuals, but similar basal collagen synthesis in monolayer cultures. Even though basal levels of collagen synthesis in collagen gel are downregulated. in a photoaging-and aging-dependent m anner, collagen synthesis by ascorbic acid in collagen gel, and by TGF -beta and IFN-gamma in both monolayer culture and collagen gel were re gulated in a photoaging-and aging-independent manner, In monolayer cul ture, however, the responsiveness to ascorbic acid in newborn fibrobla sts was greater than in photoaged and aged fibroblasts. Our results su ggest that there are differences in collagen synthesis between photoag ed and aged cells, depending on culture conditions. Responsiveness to ascorbic acid, TGF-beta and IFN-gamma related to collagen synthesis in photoaged and aged fibroblasts in collagen gel appears to be the same as in newborn fibroblasts, even though basal levels of collagen synth esis are downregulated in a photoaging-or aging-dependent manner. (C) 1997 Elsevier Science Ireland Ltd.