Abstract

It is well known that skin aging is related to the destruction of collagen and elastin fibers by metalloproteinases (MMPs). Aged fibroblasts have a decreased ability to synthesize collagen and elastin. Nuclear factor erythroid 2-related factor 2 (NRF2) involves glyoxalase (GLO) activation, which inhibits the production of advanced glycated end products (AGE) and the expression of its receptor (RAGE). RAGE increases nuclear transcription factor-kappa B (NF-κB), which upregulates MMPs and decreases skin elasticity. NRF2 also decreases M1 macrophages, which secrete tumor necrosis factor-alpha (TNF-α), thereby decreasing AGE production. It is well known that radiofrequency (RF) decreases skin elasticity by increasing collagen synthesis. We evaluated whether RF increases skin elasticity via NRF2/GLO and whether they decrease AGE and RAGE expression in aged animal skin. We also compared the effects of RF based on the modes (monopolar or bipolar) or the combination used. In aged skin, NRF2, GLO-1, and M2 macrophage expression was decreased, and their expression increased when RF was applied. M1 and TNF-α demonstrated increased expression in the aged skin and decreased expression after RF application. AGE accumulation and RAGE, NF-κB, and MMP2/3/9 expression were increased in the aged skin, and they were decreased by RF. The papillary and reticular fibroblast markers showed decreased expression in young skin and increased expression in aged skin. The densities of collagen and elastin fiber in the aged skin were low, and they were increased by RF. In conclusion, RF leads to increased collagen and elastin fibers by increasing NRF2/GLO-1 and modulating M1/M2 polarization, which leads to decreased AGE and RAGE and, consequently, decreased NF-κB, which eventually slows collagen and elastin destruction. RF also leads to increased collagen and elastin fiber synthesis by increasing papillary and reticular fibroblast expression.

Highlights

  • Skin aging is the most common cosmetic problem

  • MB represents the group of aged mice on which the monopolar mode was applied first, followed by the bipolar one after 50 ms

  • BM represents the group of aged mice on which the bipolar mode was applied first, followed by the monopolar mode (Figure 1A)

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Summary

Introduction

Skin aging is the most common cosmetic problem. It is a complex process that is caused by both intrinsic and extrinsic aging [1–4]. Known as photoaging, is a result of environmental influences, such as ultraviolet (UV) radiation or smoking [1–4]. Both of these aging processes have a common pathophysiology, which is that the skin is affected by oxidative stress or increased reactive oxygen species (ROS) [5]. Oxidative glycation, which enhances the accumulation of advanced glycated end products (AGE), increases during the skin during aging process [10]. Reactive carbonyls, such as glyoxal or methylglyoxal, and increased ROS lead to the glycation of proteins and lead to AGE formation [11,12]

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