Molecular mechanisms of intrinsic skin aging and retinoid-induced repair and reversal

Past studies have shown that topical treatment of sun-exposed skin with all-trans retinoic acid improves the clinical and histologic appearance of the skin. This is associated with a reduction in matrix metalloproteinase elaboration and with expression of a newly synthesized collagenous matrix. Whether retinoid therapy might have a similar impact on the appearance of intrinsically aged skin is not known. This study, using human skin in organ culture and epidermal keratinocytes and fibroblasts in monolayer culture, show that retinoic acid stimulates growth of both keratinocytes and fibroblasts and stimulates extracellular matrix production by the fibroblasts. Adult skin from sun-exposed and sun-protected sites responds equally well to retinoic acid, whereas neonatal skin is much less responsive under the same conditions. The implications of this are (i) that retinoids may be able to repair intrinsically aged skin as well as photoaged skin, and (ii) that retinoids modulate human skin cell function in a manner that is age-related, and not simply a response to photodamage.