EFFECTS OF ASCORBIC-ACID ON PROLIFERATION AND COLLAGEN-SYNTHESIS IN RELATION TO THE DONOR AGE OF HUMAN DERMAL FIBROBLASTS
EFFECTS OF ASCORBIC-ACID ON PROLIFERATION AND COLLAGEN-SYNTHESIS IN RELATION TO THE DONOR AGE OF HUMAN DERMAL FIBROBLASTS
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DOI：
10.1111/1523-1747.ep12393187
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发表时间：
1994-08-01
影响因子：
6.5
通讯作者：
PINNELL, SR
中科院分区：
文献类型：
--
作者：
PHILLIPS, CL;COMBS, SB;PINNELL, SR
有几个事件与细胞衰老有关：细胞外基质的改变、细胞增殖能力的丧失以及对生长因子的反应性下降。在皮肤中，细胞外基质的主要成分是胶原蛋白；抗坏血酸是胶原合成的重要调节因子，它也可能具有生长因子样的特性。为了研究细胞外基质和增殖能力与衰老的关系，我们研究了抗坏血酸对新生（3-8天）和老年（78-93岁）两种年龄供体真皮成纤维细胞细胞增殖和胶原表达的影响。在缺乏抗坏血酸（对照）的情况下，增殖能力与年龄呈负相关；新生细胞系比老年细胞系增殖更快，达到更大的密度。然而，在抗坏血酸存在的情况下，新生儿和老年细胞的增殖速度都比对照组快，密度也更高。为了确定细胞外基质生成和抗坏血酸反应是否存在与年龄相关的差异，我们检查并发现胶原蛋白生物合成（胶原酶可消化蛋白）与年龄呈负相关，但抗坏血酸的刺激似乎与年龄无关。胶原合成的增加通过稳态前α 1(I)和前α 1（III）胶原mrna的坐标增加来反映，提示存在翻译前机制。抗坏血酸似乎能够克服老年真皮成纤维细胞增殖能力的降低，并以与新生细胞相似的程度增加老年细胞的胶原合成，尽管胶原合成的基础水平与年龄有关。
Several events are associated with cellular aging: alterations in the extracellular matrix, loss of the cell's proliferative capacity, and decreased responsiveness to growth factors. In skin, a major component of the extracellular matrix is collagen; an important regulator of collagen synthesis is ascorbic acid, which may also have growth factor-like properties. To investigate the relationship of the extracellular matrix and proliferative capacity to aging, we examined the effects of ascorbic acid on cell proliferation and collagen expression in dermal fibroblasts from donors of two age classes, newborn (3-8 d old) and elderly (78-93 years old). In the absence of ascorbic acid (control) proliferative capacities were inversely related to age; newborn cell lines proliferated faster and reached greater densities than elderly cell lines. However, in the presence of ascorbic acid both newborn and elderly cells proliferated at a faster rate and reached higher densities than controls. To determine whether there are age-related differences in extracellular matrix production and ascorbic acid responsiveness we examined and found that collagen biosynthesis (collagenase-digestible protein) was inversely related to age, but the stimulation by ascorbic acid appeared age independent. The increase in collagen synthesis was reflected by coordinate increases in steady-state pro alpha 1(I) and pro alpha 1(III) collagen mRNAs, suggesting a pretranslational mechanism. Ascorbic acid appears capable of overcoming the reduced proliferative capacity of elderly dermal fibroblasts, as well as increasing collagen synthesis in elderly cells by similar degrees as in newborn cells even though basal levels of collagen synthesis are age dependent.