Acceleration of de novo cholesterol synthesis in the epidermis influences desquamation of the stratum corneum in aged mice.

Cholesterol, a component of intercellular lipids, is important for stratum corneum (SC) homeostasis, including its barrier function and desquamation. However, cholesterologenesis in the epidermis decreases under basal conditions with aging. We found that the number of horny layers in murine SC increased with the decrease of desquamation in the outermost corneocytes associated with aging. The cholesterol content decreased and the cholesterol sulfate content increased in the horny layer with aging, which resulted in an increase in the ratio of cholesterol sulfate to cholesterol. Moreover, we investigated the effects of accelerated cholesterologenesis on desquamation in aged murine skin following topical application of mevalonic acid. The ratio of cholesterol sulfate to cholesterol in aged murine SC significantly decreased following topical treatment with mevalonic acid, which resulted from an increase in cholesterol content via the acceleration of cholesterologenesis. Treatment with mevalonic acid also significantly reduced the number of cell layers in the SC along with the acceleration of desquamation, as measured by desmoglein I content, corneocyte surface area and proteinase activity. These results indicate that an improvement in the ratio of cholesterol sulfate to cholesterol content by de novo cholesterologenesis may be important for desquamation of the SC in aged epidermis.