Age-dependent changes of hyaluronan in human skin

Hyaluronan is a major component of the extracellular matrix of skin. The large volume of water of hydration associated with hyaluronan may be a mechanism for maintaining the normal hydration of skin. As such, decreasing levels of hyaluronan deposition might underlie the changes associated with the aging process. To test this hypothesis, hyaluronan levels were determined in extracts of skin obtained at autopsy from individuals of different ages. However, no significant differences in hyaluronan concentrations were found. The distribution of hyaluronan polymer sizes in various extracts did not change as a function of age as measured by size exclusion chromatography. However, major differences in hyaluronan extractability did occur as a function of age. Sequential extraction was performed utilizing 1) 0.1% Triton X-100, 2) 4 M guanidine-HCl, and 3) papain digestion, to release species of hyaluronan progressively more tightly associated with tissue. With advancing age, hyaluronan polymers became progressively more tissue associated. The proportion of hyaluronan released after papain digestion increased from 7% of the total in fetal to 23% of the total in senescent skin. Finally, histolocalization of hyaluronan was examined in full-thickness sections of human skin of different ages. Major differences in compartmentalization were found. We conclude that neither the concentration nor polymer size of hyaluronan changes as a function of age. However, enhanced association with tissue occurs, presumably through hyaluronan-binding proteins and alterations in the histolocalization of hyaluronan. Such observations may underlie some of the changes in human skin that occur with aging.