ABSTRACT: Dietary collagen hydrolysate has been conjectured to improve skin barrier function. To investigate the effect of long-term collagen hydrolysate administration on the skin, we evaluated stratum corneum water content and skin elasticity in intrinsic aged mice. Female 9-week-old hairless mice were fed a control diet, or a collagen hydrolysate-containing diet, for 12 weeks. The stratum corneum water content and skin elasticity were sequentially decreased by chronological aging in control mice. Intake of collagen hydrolysate significantly suppressed such changes. Moreover, we comprehensively analyzed gene expression in the skin of mouse, which had been administered collagen hydrolysate, using DNA microarray. Twelve weeks after start of collagen intake, no significant differences appeared in gene expression profile compared to that of control group. However, 12 weeks after administration, 135 genes were up-regulated and 448 genes were down-regulated in collagen group compared to control group. It is indicate that gene changes preceded changes of barrier function and elasticity. We focused on several genes correlated with functional changes in the skin. Gene Ontology terms, especially related to epidermal cell development, were signi?cantly enriched in up-regulated genes. These skin function-related genes had properties that facilitate epidermal production and differentiation and suppress dermal degradation. Thus, dietary collagen hydrolysate induced positive gene changes. In conclusion, our results suggest that alteration of gene expression at early stages after collagen administration affect skin barrier function and mechanical properties. Long-term oral intake of collagen hydrolysate improves skin dysfunction by regulating genes related to production and maintenance of the skin tissue. Nine-week-old female Hos:HR-1 hairless mice (Japan SLC Inc., Shizuoka, Japan) were used in this study. All mice were housed in plastic cages (4 mice/cage) in a temperature and humidity controlled room (24 ± 1°C and 50 ± 10% humidity) under a 12 hour light-dark cycle. Mice were given an AIN-93G (Oriental Yeast Co., Ltd., Tokyo, Japan) diet and water. The present study was approved by the Animal Committee of Meiji Seika Kaisha Ltd., Food & Health R&D Laboratories, with the animals receiving care under the Guiding Principles for the Care and Use of Laboratory Animals of this committee. All surgery was performed under isoflurane anesthesia, and all efforts were made to minimize suffering. Sixteen female mice were randomly divided into two groups (n = 8 /group) according to their body weight, stratum corneum water content, and skin elasticity. During the experimental period for 12 weeks, the control group was fed a control diet (AIN-93G) and the collagen group was fed a collagen diet consisting of a mixture of 2.0 g of collagen hydrolysate and 100 g of the control diet. Fish scale collagen hydrolysate was purchased from Nitta Gelatin Inc. (Osaka, Japan). This amount of collagen hydrolysate is approximately equivalent to oral ingestion of 2.0 g collagen hydrolysate/kg body weight/day.
