Stratum corneum acidification is impaired in moderately aged human and murine skin.
Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that could be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. This defect is linked to reduced epidermal lipid synthesis in humans and in mice of advanced age (i.e., >75 years in human or >18-24 months in mice). We now report that barrier defects in moderately aged humans (50-80 years) or analogously aged mice (12-15 months) are linked instead to defective stratum corneum (SC) acidity. In moderately aged mouse epidermis, we find that abnormal acidification, in turn, is linked to decreased Na+/H+ antiporter (NHE1) expression. Decreased NHE1 levels lead to increased SC pH, which results in defective lipid processing and delayed maturation of lamellar membranes, due to suboptimal activation of the pH-sensitive essential, lipid-processing enzyme, beta-glucocerebrosidase. Conversely, impaired SC integrity in moderately aged mice is due to increased pH-dependent activation of serine proteases, leading to premature degradation of corneodesmosomes. These abnormalities were normalized by exogenously acidifying the SC, suggesting a basis for the well-known acidification therapies that are widely used to treat the pathologic xerosis/eczema seen in moderately aged humans.
Choi
Eung-Ho
EH
Department of Dermatology, University of California San Francisco and Dermatology Service, Veteran's Administration Medical Center, San Francisco, California 94121, USA.
Man
Mao-Qiang
MQ
Xu
Pu
P
Xin
Shujun
S
Liu
Zhili
Z
Crumrine
Debra A
DA
Jiang
Yan J
YJ
Fluhr
Joachim W
JW
Feingold
Kenneth R
KR
Elias
Peter M
PM
Mauro
Theodora M
TM
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000818:Animals; D027682:Cation Transport Proteins / Q000502:physiology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008954:Models, Biological; D012737:Sex Factors; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D027682:Cation Transport Proteins; D008565:Membrane Proteins; C490998:SLC9A1 protein, human; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers