**3.3 Physiological lipids**

Lipids play a crucial role in the water-impermeable barrier function of the skin. Damaged barrier function can be restored by topical application of a water-impermeable substance such as petrolatum (Man 1995). In this case, the petrolatum stays in the stratum corneum and forms a water-impermeable membrane. However, Man et al. demonstrated that a topically applied mixture of stratum corneum lipids, i.e., ceramide, cholesterol and free fatty acids, was incorporated in the nucleated layer of epidermis and accelerated repair of the barrier function after damage (Man 1996). They were the first to report a method to accelerate the barrier recovery by regulating endogenous factors in the epidermis. Interestingly, when they applied ceramide, cholesterol, or free fatty acid alone, or a mixture of two of these, the barrier recovery was delayed. Only when they applied a mixture of all three lipids at a specific relative ratio was the barrier recovery accelerated (Man 1996). These results suggest that a balance of the three lipids is crucial for skin barrier homeostasis.


Table 1. Summary of the effects of physical, chemical and biological factors on skin permeability barrier recovery.

In the case of aging, different treatment might be necessary because of the different metabolism of aged skin. Ghadially et al. demonstrated that skin barrier function in elderly subjects was destroyed more easily than that in young individuals (Ghadially 1995). Moreover, the barrier recovery rate after barrier disruption was significantly slower for the elderly subjects than for younger ones. The same tendency was observed in both humans and hairless mice. They also suggested that synthesis of cholesterol is reduced more than that of other lipids, i.e., ceramide and fatty acids, in aged mice. The delay of barrier recovery with aging was improved by topical application of cholesterol (Ghadially 1996) or mevalonic acid (Haratake 2000), presumably because the delay of the aged skin was caused by a decrease of cholesterol synthesis.
