Phillips C L, Combs S B, Pinnell S R
Duke University Medical Center, Department of Medicine, Durham, NC 27710.
J Invest Dermatol. 1994 Aug;103(2):228-32. doi: 10.1111/1523-1747.ep12393187.
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.
细胞外基质的改变、细胞增殖能力的丧失以及对生长因子反应性的降低。在皮肤中，细胞外基质的主要成分是胶原蛋白；胶原蛋白合成的一个重要调节因子是抗坏血酸，它可能还具有生长因子样特性。为了研究细胞外基质和增殖能力与衰老之间的关系，我们检测了抗坏血酸对来自两个年龄组供体（新生儿（3 - 8日龄）和老年人（78 - 93岁））的真皮成纤维细胞增殖和胶原蛋白表达的影响。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且达到更高密度。然而，在有抗坏血酸存在时，新生和老年细胞均比对照增殖更快且达到更高密度。为了确定细胞外基质产生和抗坏血酸反应性是否存在与年龄相关的差异，我们进行了检测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。胶原蛋白合成的增加表现为稳态的原α1（I）和原α1（III）胶原蛋白mRNA协同增加，提示存在转录前机制。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，并且在老年细胞中增加胶原蛋白合成，其增加程度与新生细胞相似，尽管胶原蛋白合成的基础水平依赖于年龄。
