title: Optimal ratios of topical stratum corneum lipids improve barrier recovery in chronologically aged skin.
abstract: BACKGROUND
  Chronologically aged skin exhibits delayed recovery rates after defined barrier insults, with decreased epidermal lipid synthesis, and particularly a reduction in cholesterol synthesis. Prior studies in young mice (< 10 weeks) and humans (20 to 30 years of age) have shown that application of a mixture of cholesterol, ceramides, and essential/nonessential free fatty acids (FFAs) in an equimolar ratio allows normal barrier recovery, whereas any 3:1:1:1 ratio of these four ingredients accelerates barrier recovery.
  
  
  OBJECTIVE
  Our purpose was to compare the ability of equimolar and cholesterol- and FFA-dominant molar lipid mixtures (2% in propylene glycol/n-propanol, 7:3) versus 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
  Whereas a single topical application of the equimolar mixture only allows normal recovery in young mice, it appeared to improve barrier recovery in chronologically aged mice (p < 0.06). Moreover, a 3:1:1:1 mixture with cholesterol as the dominant lipid further accelerated barrier recovery 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 significantly accelerated barrier recovery in chronologically aged human skin at 6 hours (p < 0.005; n = 6). In contrast, in aged mice, an FFA-dominant mixture significantly delayed barrier recovery at 3, 6, and 24 hours (p < 0.005, 0.05, and 0.001, respectively), Finally, ultrastructural studies showed that lipid-induced, accelerated recovery in chronologically aged mice is associated with the accelerated replenishment of the stratum corneum interstices with lamellar unit structures.
  
  
  CONCLUSIONS
  These findings show that barrier recovery is accelerated in chronologically aged murine epidermis with optimized ratios of physiologic lipids, provided that cholesterol is the dominant lipid and that the same mixture also accelerates barrier recovery in chronologically aged human skin.
authors.affiliation: Department of Dermatology, University of California School of Medicine, San Francisco, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Zettersten
authors.forename: R
authors.initials: R
authors.lastname: Ghadially
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
authors.forename: D
authors.initials: D
authors.lastname: Crumrine
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002518:Ceramides / Q000008:administration & dosage; D002784:Cholesterol / Q000008:administration & dosage; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D015595:Skin Aging / Q000502:physiology*; D012879:Skin Physiological Phenomena; D014870:Water Loss, Insensible
chemical_list: D002518:Ceramides; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D002784:Cholesterol