**7. Aging-dependent changes of versican in the dermal connective tissues**

The dermis changes prominently with age; for example, the thickness of the dermis becomes thin and wrinkles appear. Biochemical collagen content and histological density of collagen fiber is reduced (23). We have shown that versican is a key molecule for viscoelasticity of the dermis. The amount of versican extracted from the dermis decreases with age and its GAG composition is also altered (24, 25). Therefore, as described above, we hypothesize that loss or reduction of versican, or in the HA binding ability of versican, may lead to impaired viscoelasticity of the dermis. Versican is heavily accumulated within solar elastosis, which is a hallmark of photo-aged skin and where elastic fiber components, including elastin and fibrillin-1, have accumulated (26). Clinically, photo-aged skin is not viscoelastic and shows deep wrinkles, as observed in Figure 12.

Using recombinant versican G1 proteins and specific antibodies, we have indicated that a loss in the HA binding affinity of versican is characteristically observed in the region of solar elastosis (27). Versican specifically loses its HA binding domain (6084) in solar elastosis, whereas the carboxyl terminal domain (2B1) remains present. Therefore, the HA binding ability of elastic fibers is lost and microfibrils in solar elastosis are unable to bind to HA (Figure 13). Therefore, loss of the HA binding region of versican disrupts the fibrillinversican-hyaluronan (Fi-Ver-Hy) network in the dermis.

**Figure 12.** Clinical appearance of photo-aged skin. Deep wrinkles and comedo (black dots) are observed.

**Figure 13.** Histochemical results of solar elastosis. Versican is detected by its anti-fibrillin binding region (2B1) or its anti-HA binding region (6084). HA is detected using a biotin-conjugated link protein (biotin LP).
