1145 Acute UV irradiation and intrinsic aging modulate various histone deacetylases expression levels in human skin in vivo

Abstract

Epigenetic regulation is widely considered to play an important role in aging, but experimental evidence to support this hypothesis for skin aging in vivo is scarce. Histone deacetylases(HDACs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. There are 11 HDACs and 7 sirtuins(Sirts) as histone deacetylases that play a critical role in epigenetics. Previously, our group demonstrated the role of histone acetylation in UV-induced inflammation and matrix impairment. Here, to understand the histone acetylation alterations occurring during the aging process, we investigated the changes HDACs and Sirts expressions in UV-irradiated human skin, and the intrinsically aged and photoaged human skin in vivo. We found that acetyl-H3 level was increased and HDAC4, 11, and Sirt4 mRNA were significantly deceased in UV-irradiated skin. In intrinsically aged skin, acetyl-H3 level was increased and HDAC4, 5, 10, 11, and Sirt6, 7 mRNA were significantly deceased. However, histone acetylation and HDACs expressions in photoaged forearm skin were not different from those in intrinsically aged buttock skin in the same individuals. Thus, our results suggested that decreased HDACs expression by acute UV irradiation and intrinsic aging may contribute to increased histone acetylation. Therefore, epigenetic regulation that reduces histone acetylation by increasing the expression of HDACs may prevent skin aging.