Abstract
Histone deacetylases (HDACs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins and play a crucial role in epigenetic regulation. Previously, we showed that histone acetylation is implicated in ultraviolet (UV)-induced inflammation and matrix impairment. To elucidate the histone acetylation status and specific HDACs involved in skin aging, we examined the changes in histone acetylation, global HDAC activity, and the expression of HDACs and sirtuins (SIRTs) in intrinsically aged and photoaged human skin as well as in UV-irradiated human skin in vivo. Following acute UV irradiation, the acetylated histone H3 (AcH3) level was increased, but HDAC activity and the expression levels of HDAC4, HDAC11, and SIRT4 were significantly decreased. In intrinsically aged skin, AcH3 levels were increased, but HDAC activity and the expression levels of HDAC4, HDAC5, HDAC10, HDAC11, SIRT6, and SIRT7 were significantly decreased. However, histone acetylation and HDAC expression in photoaged skin were not significantly different from those in intrinsically aged skin. Collectively, HDAC4 and HDAC11 were decreased in both UV-irradiated and intrinsically aged skin, suggesting that they may play a universal role in increased histone acetylation associated with skin aging.
Highlights
Skin is a multifunctional organ with diverse regulatory properties and operates as a barrier between the external environment and internal milieu [1,2]
We previously showed that UV irradiation of human dermal fibroblasts increased
We investigated whether histone acetylation status, global Histone deacetylases (HDACs) enzyme activity, we and investigated whether histone acetylation status, global enzyme activity, and
Summary
Skin is a multifunctional organ with diverse regulatory properties and operates as a barrier between the external environment and internal milieu [1,2]. Physiological changes in the skin are affected by intrinsic and extrinsic factors. Ultraviolet (UV) light is the most well-characterized extrinsic factor that aggravates skin aging. Exposure of human skin to UV light modulates the synthesis of extracellular matrix proteins, such as procollagen, elastin, and fibrillin-1. It induces the expression of matrix metalloproteinases (MMPs), leading to degradation of the extracellular matrix during skin aging [4,5,6,7]. Intrinsic aging and photoaging share several molecular changes, such as altered signal transduction pathways that promote the expression of MMPs and decrease the synthesis of procollagen [11]
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