Chapter 26: Cosmetic Dermatology

SKIN AGING

• Intrinsic aging: natural or chronologic aging, influenced by genetics

  • Begins in the mid-20s, but signs may not be visible for decades

  • Collagen production and cell turnover slows

  • Loss of subcutaneous fat and bone loss contribute to volume issues

• Extrinsic aging: caused by environmental factors

  • Largest contributors are ultraviolet (UV) radiation (photoaging) and smoking

  • Facial expressions, sleeping positions, nutrition, and airborne particles (pollution) are additive factors

  • Solar elastosis or dermatoheliosis: term applied to the chronic inflammatory changes and degradation of elastin and collagen

OXIDATIVE STRESS (FREE RADICAL THEORY OF AGING)

• Reactive oxygen species (ROS) derived from the environment and oxidative cell metabolism damage cellular components and lead to aging

  • Mitochondria are the main endogenous source of ROS

• ROS activate signal transduction pathways including mitogen-activated protein kinases, c-jun N-terminal kinase (JNK), and extracellular signal related kinases, which upregulate the nuclear transcription factor activator protein 1 (AP-1)

• AP-1 activates matrix metalloproteinase (MMP) genes for MMP-1 (collagenase), MMP-3 (stromolysin), and MMP-9 (gelatinase)

• MMPs degrade collagen types I and III

• AP-1 inhibits transforming growth factor B (TGF-B), a profibrotic cytokine, and downregulates type II TGF-B receptors so cells cannot respond to TGF-B and less type I procollagen is produced

• Antioxidants such as vitamins A, C, and E, ubiquinone and glutathione may help to minimize ROS-induced damage

• All-trans-retinoic acid (tretinoin) acts like an antioxidant to inhibit the accumulation of c-jun protein, thereby preventing the formation of AP-1 and the upregulation of MMPs

• Tretinoin also induces TGF-B to enhance production of procollagen types I and III

Ultraviolet Radiation

• UVA: 320 to 400 nm; largest contributor to Aging due to deeper penetration depth and ability to generate ROS

  • UVA1: 340 to 400 nm (longest wavelength and deepest penetration of all ultraviolet light)

  • UVA2: 320 to 340 nm

• UVB: 290 to 320 nm; Burning rays; absorbed by the epidermis, mainly causing damage to keratinocytes in the form of pyrimidine dimers

  • Narrowband UVB: 311 to 312 nm

  • UVC: 100 to 290 nm; has negligible effect on skin as nearly all is blocked by the atmosphere

• UVA rays make up 95% of UV radiation reaching the Earth's surface; however UVB rays are more intense

• Both contribute to skin cancer, photoaging (wrinkles, discoloration, telangiectasias), and ocular changes (cataracts, pterygium)

• UV radiation downregulates gene expression in types I and III procollagen in dermal fibroblasts

• UV radiation activates transcription factor nuclear factor κB (NF-κB), resulting in transcription of proinflammatory cytokines such as IL-1β, tumor necrosis factor α, IL-6, and IL-8. Proinflammatory cytokines bind receptors on the cell surface to further activate AP-1 and NF-κB, escalating the photoaging response

• Activation of MMP-1 and NF-κB are iron dependent mechanisms, so iron chelators such as kojic acid may be included in topical antiaging preparations

Telomeres and Aging

• Telomeres form the ends of human chromosomes; defend the ends of chromosomes ...