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自然老化皮肤中胶原蛋白生成减少:成纤维细胞功能随年龄变化及机械刺激缺陷的作用

Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation.

作者信息

Varani James, Dame Michael K, Rittie Laure, Fligiel Suzanne E G, Kang Sewon, Fisher Gary J, Voorhees John J

机构信息

Department of Pathology, The University of Michigan, 1301 Catherine Rd./Box 0602, Ann Arbor, MI 48109 USA.

出版信息

Am J Pathol. 2006 Jun;168(6):1861-8. doi: 10.2353/ajpath.2006.051302.

Abstract

Reduced synthesis of collagen types I and III is characteristic of chronologically aged skin. The present report provides evidence that both cellular fibroblast aging and defective mechanical stimulation in the aged tissue contribute to reduced collagen synthesis. The reduction in collagen synthesis due to fibroblast aging was demonstrated by a lower in vitro production of type I procollagen by dermal fibroblasts isolated from skin of young (18 to 29 years) versus old (80+ years) individuals (82 +/- 16 versus 56 +/- 8 ng/ml; P < 0.05). A reduction in mechanical stimulation in chronologically aged skin was inferred from morphological, ultrastructural, and fluorescence microscopic studies. These studies, comparing dermal sections from young and old individuals, demonstrated a greater percentage of the cell surface attached to collagen fibers (78 +/- 6 versus 58 +/- 8%; P < 0.01) and more extensive cell spreading (1.0 +/- 0.3 vs. 0.5 +/- 0.3; P < 0.05) in young skin compared with old skin. These features are consistent with a lower level of mechanical stimulation on the cells in old versus young skin. Based on the findings presented here, we conclude that reduced collagen synthesis in chronologically aged skin reflects at least two different underlying mechanisms: cellular fibroblast aging and a lower level of mechanical stimulation.

摘要

I型和III型胶原蛋白合成减少是自然老化皮肤的特征。本报告提供了证据表明,成纤维细胞老化和老化组织中机械刺激缺陷均导致胶原蛋白合成减少。通过比较从年轻(18至29岁)与老年(80岁以上)个体皮肤分离的真皮成纤维细胞I型前胶原的体外产量,证实了由于成纤维细胞老化导致的胶原蛋白合成减少(分别为82±16和56±8 ng/ml;P<0.05)。通过形态学、超微结构和荧光显微镜研究推断,自然老化皮肤中的机械刺激减少。这些比较年轻和老年个体真皮切片的研究表明,与老年皮肤相比,年轻皮肤中附着于胶原纤维的细胞表面百分比更高(分别为78±6和58±8%;P<0.01),细胞铺展更广泛(分别为1.0±0.3和0.5±0.3;P<0.05)。这些特征与老年皮肤与年轻皮肤中细胞受到的机械刺激水平较低一致。基于此处呈现的研究结果,我们得出结论,自然老化皮肤中胶原蛋白合成减少反映了至少两种不同的潜在机制:成纤维细胞老化和机械刺激水平降低。

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