OPTIMAL RATIOS OF TOPICAL STRATUM-CORNEUM LIPIDS IMPROVE BARRIER RECOVERY IN CHRONOLOGICALLY AGED SKIN

Background: Chronologically aged skin exhibits delayed recovery rates after defined barrier insults, with decreased epidermal lipid synthesi s, and particularly a reduction in cholesterol synthesis. Prior studie s in young mice (< 10 weeks) and humans (20 to 30 years of age) have s hown that application of a mixture of cholesterol, ceramides, and esse ntial/nonessential free fatty acids (FFAs) in an equimolar ratio allow s normal barrier recovery, whereas any 3:1:1:1 ratio of these four ing redients accelerates barrier recovery. Objective and methods: Our purp ose was to compare the ability of equimolar and cholesterol-and FFA-do minant molar lipid mixtures (2% in propylene glycol/n-propanol, 7:3) v ersus vehicle alone on barrier recovery rates at 0, 3, 6, 24, 48 hours , and 1 week after tape stripping of aged hairless mouse (> 18 months) and chronologically aged human skin (80 +/- 5 years). Results: Wherea s a single topical application of the equimolar mixture only allows no rmal recovery in young mice, it appeared to improve barrier recovery i n chronologically aged mice (p < 0.06). Moreover, a 3:1:1:1 mixture wi th cholesterol as the dominant lipid further accelerated barrier recov ery at 3 and 6 hours (p < 0.01 and p < 0.03, respectively, vs 1:1:1:1) . Likewise, the cholesterol-dominant, optimal molar ratio mixture sign ificantly accelerated barrier recovery in chronologically aged human s kin at 6 hours (p < 0.005; n = 6). In contrast, in aged mice, an FFA-d ominant mixture significantly delayed barrier recovery at 3, 6, and 24 hours (p < 0.005, 0.05, and 0.001, respectively). Finally, ultrastruc tural studies showed that lipid-induced, accelerated recovery in chron ologically aged mice is associated with the accelerated replenishment of the stratum corneum interstices with lamellar unit structures. Conc lusion: These findings show that barrier recovery is accelerated in ch ronologically aged murine epidermis with optimized ratios of physiolog ic lipids, provided that cholesterol is the dominant lipid and that th e same mixture also accelerates barrier recovery in chronologically ag ed human skin.