Effect of orally administered collagen hydrolysate on gene expression profiles in mouse

26 Dietary collagen hydrolysate has been hypothesized to improve skin barrier function. To 27 investigate the effect of long-term collagen hydrolysate administration on the skin, we 28 evaluated stratum corneum water content and skin elasticity in intrinsically aged mice. 29 Female hairless mice were fed a control diet or a collagen hydrolysate-containing diet for 30 12 weeks. Stratum corneum water content and skin elasticity were gradually decreased in 31 chronologically aged control mice. Intake of collagen hydrolysate significantly suppressed 32 such changes. Moreover, we analyzed gene expression in the skin of mice that had been 33 administered collagen hydrolysate using DNA microarrays. Twelve weeks after the start of 34 collagen intake, no significant differences appeared in the gene expression profile compared 35 to the control group. However, 1 week after administration, 135 genes were up-regulated 36 and 448 genes were down-regulated in the collagen group. This suggests that gene changes 37 preceded changes of barrier function and elasticity. We focused on several genes correlated 38 with functional changes in the skin. Gene Ontology terms related to epidermal cell 39 development were significantly enriched in up-regulated genes. These skin function-related 40 genes had properties that facilitate epidermal production and differentiation while 41 suppressing dermal degradation. In conclusion, our results suggest that altered gene 42 expression at the early stages after collagen administration affects skin barrier function and 43 mechanical properties. Long-term oral intake of collagen hydrolysate improves skin 44 dysfunction by regulating genes related to production and maintenance of skin tissue. 45