S100A8, a calcium-binding protein, is associated with keratinocyte differentiation, inflammation and wound healing. S100A8 is induced by various skin stresses and diseases, which suggests that S100A8 plays a role in those processes. However, it has not been reported how the expression of S100A8 is affected during skin aging or whether S100A8 plays a role in the skin aging process. In this study, we investigated the changes in S100A8 mRNA and protein following acute UV irradiation to human buttock skin and by intrinsic aging and photoaging in human sun-protected (upper-inner arm) and sun-exposed (forearm) skin of elderly subjects. Real-time PCR, western blot and immunohistochemical staining analyses of UV-irradiated young buttock skin revealed that S100A8 protein expression was increased at 24 h (3.0-fold) and 48 h (4.4-fold) after UV irradiation. S100A8 mRNA and protein were more highly expressed by 2.3- and 4.0-fold, respectively, in the sun-protected skin of elderly people than in that of young people. In addition, the sun-exposed skin of elderly expressed more S100A8 mRNA and protein than the sun-protected skin of the same individuals. In immunohistochemical staining, facial (photoaged) skin > or = 72 years showed higher epidermal expression of S100A8 than that of the other age groups. Based on the above results, our data suggest that the expression of S100A8 is affected by acute UV irradiation, intrinsic aging and photoaging processes.