Chapter 17 – Hyaluronan in Aging

Hyaluronan (HA) is an essential heteropolysaccharide of mammalian connective tissue. In this chapter, the secondary and tertiary structures of HA in solution are analyzed, in an attempt to explain their relevance to normal biologic functions and aging. Hydrophilic sequences of D-GlcN and D-GlcA are used to explain the stiff and flexible domains detected in HA solutions. The hydrophilic segments should be more densely hydrogen bonded with water than the regions of alternating D-GlcA and D-GlaNAc, as water would form cages around them. In aging, the hypothetic D-GlcN sequence is used in an attempt to explain the N-deacetylation of human skin HA at 75 years of age. Because the skin composition of HA decreases by 77% (w/w), also at 75 years, and the basic sugarsequence makes HA more hydrophilic than the alternating sequence of D-GlcA and D-GlcNAc, it is concluded that nature compensates for the loss of HA concentration in aging by having an enzyme that removes the N-acetyl groups, making HA more hydrophilic. Highly hydrophilic HA is needed in aged human skin, if no other molecules are made to retain the water, since about 50% (w/w) of this reagent is bonded to this GAG. The reasons for the loss of HA from the skin were attributed to depolymerization induced by both endogenous and exogenous free radicals. This hypothesis is supported by findings that indicate that free radical scavengers inhibit UV-light-mediated cleavage of HA in vitro.