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(American Journal of Pathology. 2006;168:1861-1868.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.051302

Decreased Collagen Production in Chronologically Aged Skin

Roles of Age-Dependent Alteration in Fibroblast Function and Defective Mechanical Stimulation

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

From the Departments of Pathology^* and Dermatology, The University of Michigan, Ann Arbor, Michigan

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.

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