Retinoic acid receptor alpha expression and cutaneous ageing.

Intrinsic ageing of human skin is a subtle and gradual process that demonstrates few clinical or histological features until old age (>70 years). Initial work indicates that aged skin is "retinoid sensitive" but there is little data on the role of retinoic acid receptors (RARs) or retinoid X receptors (RXRs) in skin ageing. As nuclear retinoid receptors have been implicated in ageing in rodents, we studied the distribution of these receptors in intrinsically aged as compared to young, photoprotected human skin. We found that intrinsic ageing of skin in vivo is accompanied by significant increases of RARα mRNA and protein whereas other isoforms show no alteration with age. In vitro transfection of COS-1 cells with the RARα gene induces expression of matrix metalloproteinase-1 (MMP-1), an enzyme known to play an active role in remodelling of the dermis in intrinsically aged and photoaged skin. Furthermore, addition of all-trans retinoic acid (RA) to cultures of RARα-transfected COS-1 cells diminishes RARα and returns levels of MMP-1 to those approaching baseline. These results demonstrate that intrinsic ageing of human skin is accompanied by significant elevation in the content of RARα and that over-expression of RARα influences expression of MMP-1, an important mediator of skin ageing. © 2004 Elsevier Ireland Ltd. All rights reserved.