Fighting against Skin Aging: The Way from Bench to Bedside

Shoubing Zhang, Enkui Duan, Shoubing Zhang, Enkui Duan

Abstract

As the most voluminous organ of the body that is exposed to the outer environment, the skin suffers from both intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, laxity, and rough-textured appearance. This aging process is accompanied with phenotypic changes in cutaneous cells as well as structural and functional changes in extracellular matrix components such as collagens and elastin. In this review, we summarize these changes in skin aging, research advances of the molecular mechanisms leading to these changes, and the treatment strategies aimed at preventing or reversing skin aging.

Keywords: extracellular matrix; extrinsic aging; intrinsic aging; skin aging; treatment strategy.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Molecular mechanisms of reactive oxygen species (ROS) in skin aging. (A) Under common conditions without ligands, the activity of receptor tyrosine kinases (RTKs) on the cell surface is inhibited by receptor protein tyrosine phosphatases (RPTPs), which dephosphorylate RTKs and keep low levels of signaling, producing a normal amount of collagen and matrix metalloproteinases (MMPs). (B) Under ultraviolet radiation, ROS are produced, which inhibit the activity of RPTPs by binding to the catalytic sites of RPTPs, elevating the level of phosphorylated RTKs and triggering downstream signaling pathways including the activation of mitogen-activated protein kinase (MAPK) and subsequent nuclear factor-κB (NF-κB) and transcription factor activator protein-1 (AP-1). NF-κB and AP-1 increase MMP gene transcription, and AP-1 downregulates the expression of transforming growth factor-β (TGF-β) type II receptor, resulting in the reduced phosphorylation of transcription factor Smads and the subsequent repression of the collagen production. Thus, the total collagen content in photoaged skin decreases. Antioxidants can neutralize ROS, prevent its binding to RPTPs, and restore the signaling back to normal levels. This diagram is revised from Rittie and Fisher and Kammeyer and Luiten.
Figure 2.
Figure 2.
A model proposed to explain the mechanism of inflammaging in skin. (A) Ultraviolet (UV) radiation induces oxidative stress in epidermal cells, resulting in damaged cells with oxidized lipids. Oxidation-specific epitopes on damaged cells and oxidized lipids activate complement systems and cause inflammation, leading to infiltration and activation of macrophages. Activated macrophages release matrix metalloproteinases (MMPs) to degrade extracellular matrix. (B) Repeated UV radiation overactivates the complement system, causing damage to the dermis–epidermis junction, on which they deposit, and macrophages are overburdened with oxidized lipids. Overburdened macrophages release proinflammatory cytokines and reactive oxygen species (ROS), the former of which cause chronic inflammation and long-term damage to the dermis, while the latter triggers the oxidative stress-induced damages to the dermal extracellular matrix. This schematic diagram is revised from Zhuang and Lyga60.

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