Retinoic acid receptor α 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 RARalpha mRNA and protein whereas other isoforms show no alteration with age. In vitro transfection of COS-1 cells with the RARalpha 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 RARalpha-transfected COS-1 cells diminishes RARalpha 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 RARalpha and that over-expression of RARalpha influences expression of MMP-1, an important mediator of skin ageing. (C) 2004 Elsevier Ireland Ltd. All rights reserved.