THE AGED EPIDERMAL PERMEABILITY BARRIER - STRUCTURAL, FUNCTIONAL, ANDLIPID BIOCHEMICAL-ABNORMALITIES IN HUMANS AND A SENESCENT MURINE MODEL

Aged epidermis displays altered drug permeability, increased susceptib ility to irritant contact dermatitis, and often severe xerosis, sugges ting compromise of the aged epidermal barrier. To delineate the functi onal, structural, and lipid biochemical basis of epidermal aging, we c ompared barrier function in young (20-30 yr) vs aged (> 80 yr) human s ubjects, and in a murine model. Baseline transepidermal water loss in both aged humans and senescent mice was subnormal. However, the aged b arrier was perturbed more readily with either acetone or tape strippin g (18+/-2 strippings vs 31+/-5 strippings in aged vs young human subje cts, respectively). Moreover, after either acetone treatment or tape s tripping, the barrier recovered more slowly in aged than in young huma n subjects (50 and 80% recovery at 24 and 72 h, respectively, in young subjects vs 15% recovery at 24 h in aged subjects), followed by a fur ther delay over the next 6 d. Similar differences in barrier recovery were seen in senescent vs young mice, Although the total lipid content was decreased in the stratum corneum of aged mice (similar to 30%), t he distribution of ceramides (including ceramide 1), cholesterol, and free fatty acids was unchanged, Moreover, a normal complement of ester ified, very long-chain fatty acids was present. Finally, stratum corne um lamellar bilayers displayed normal substructure and dimensions, but were focally decreased in number, with decreased secretion of lamella r body contents. Thus, assessment of barrier function in aged epidermi s under basal conditions is misleading, since both barrier integrity a nd barrier repair are markedly abnormal. These functional changes can be attributed to a global deficiency in all key stratum corneum lipids , resulting in decreased lamellar bilayers in the stratum corneum inte rstices. This constellation of findings may explain the increased susc eptibility of intrinsically aged skin to exogenous and environmental i nsults.