Overview of Skin Aging and Photoaging

Yolanda Rosi Helfrich, MD; Dana L. Sachs, MD; John J. Voorhees, MD

Disclosures

Dermatology Nursing. 2008;20(3):177-183. 

In This Article

Mechanism of Photoaging

Collagen is one of the main building blocks of human skin, providing much of the skin's strength. Dermal fibroblasts make precursor molecules called procollagen, which is converted into collagen. There are two important regulators of collagen production: transforming growth factor (TGF)-b and activator protein (AP)-1. TGF-b is a cytokine that promotes collagen production (MassaguE9, 1998). AP-1 is a transcription factor that inhibits collagen production and up-regulates collagen breakdown (Kang, Fisher, & Voorhees, 1997). Collagen in skin undergoes continuous skin remodeling and turnover, with TGF-b and AP-1 playing important roles. TGF-b promotes collagen formation, while AP-1 promotes collagen breakdown by up-regulating enzymes called matrix metalloproteinases (MMPs).

When skin is exposed to sunlight, UV radiation is absorbed by skin molecules that can generate harmful compounds, called reactive oxygen species (ROS), which then cause "oxidative damage" to cellular components like cell walls, lipid membranes, mitochondria, and DNA. These ROS also play an important role in molecular pathways. Irradiation of human buttock skin with 2 MED (two times the dose of UVA/UVB that causes barely perceptible skin reddening, the minimal erythema dose) causes increased generation of hydrogen peroxide, an ROS, within 15 minutes (Kang et al., 2003). Within the same time frame, AP-1, which leads to increased collagen breakdown, becomes elevated and remains elevated for at least 24 hours following UV irradiation (Fisher et al., 1996). Collagen-degrading MMPs, which are up-regulated by AP-1, are also markedly elevated within 24 hours of UV irradiation (Fisher et al., 1996). Within 24 hours of a single dose of UV irradiation, increased collagen breakdown can be demonstrated (Fisher et al., 1997).

To summarize, UV irradiation leads to generation of ROS and induction of AP-1, which causes increased MMP production, with subsequent increased breakdown of collagen. In addition, UV irradiation leads to decreased expression of TGF-b2, a member of the TGF-b family. As noted previously, TGF-b promotes collagen formation; therefore, decreased expression of TGF-b causes decreased collagen production. Researchers have demonstrated decreased procollagen synthesis within 8 hours of UV irradiation (Quan, He, Kang, Voorhees, & Fisher, 2002). Increased breakdown and decreased production of collagen are the cornerstones of photoaging. Each UV insult induces a wound response with subsequent imperfect repair, leaving an invisible "solar scar." Repetitive UV insults over a lifetime eventually lead to development of a visible "solar scar," manifesting as a visible wrinkle (Kang, Fisher, & Voorhees, 2001) (see Figure 1).

Model Depicting the Effect of Ultraviolet Radiation on Skin. Acute ultraviolet irradiation leads to generation of ROS, upregulation of AP-1, and downregulation of TGF-b. AP-1 leads to collagen breakdown, while decreased TGF-b activity is associated with decreased collagen production. No damage to the skin is repaired perfectly; acute solar damage leads to an invisible solar scar. Repeated ultraviolet irradiation and injury eventually leads to accumulation of damage, eventually manifesting as a visible solar scar, or a wrinkle associated with photoaging.

It is commonly accepted that increased innate pigmentation (darker skin tone) is associated with protection from sun damage. Darker-skinned people are less likely to develop a sunburn after intense sun exposure, and have a lower incidence of skin cancer. In addition, darkly pigmented subjects have significantly less induction of collagen breakdown and less DNA damage than lightly pigmented subjects (Fisher et al., 2002). These molecular findings support the clinical observation that darker-skin pigmentation protects against photoaging.

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