Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation - a review

• Published in: International journal of cosmetic science 2005-02, Vol.27 (1), p.17-34
• Main Authors: Pillai, S., Oresajo, C., Hayward, J.
• Format: Article
• Language: English
• Subjects: antipotease; Biological and medical sciences; Dermatology; elastase; matrix metalloprotease; Medical sciences; neutrophils; serine protease; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0142-5463; 1468-2494; 1467-2494
• DOI: 10.1111/j.1467-2494.2004.00241.x

Synopsis Inflammation and the resulting accumulation of reactive oxygen species (ROS) play an important role in the intrinsic and photoaging of human skin in vivo. Environmental insults such as ultraviolet (UV) rays from sun, cigarette smoke exposure and pollutants, and the natural process of aging contribute to the generation of free radicals and ROS that stimulate the inflammatory process in the skin. UV irradiation initiates and activates a complex cascade of biochemical reactions in human skin. In short, UV causes depletion of cellular antioxidants and antioxidant enzymes (SOD, catalase), initiates DNA damage leading to the formation of thymidine dimmers, activates the neuroendocrine system leading to immunosuppression and release of neuroendocrine mediators, and causes increased synthesis and release of pro‐inflammatory mediators from a variety of skin cells. The pro‐inflammatory mediators increase the permeability of capillaries leading to infiltration and activation of neutrophils and other phagocytic cells into the skin. The net result of all these effects is inflammation and free radical generation (both reactive oxygen and nitrogen species). Furthermore, elastsases and other proteases (cathepsin G) released from neutrophils cause further inflammation, and activation of matrix metalloproteases. The inflammation further activates the transcription of various matrixes degrading metalloproteases, leading to abnormal matrix degradation and accumulation of non‐functional matrix components. In addition, the inflammation and ROS cause oxidative damage to cellular proteins, lipids and carbohydrates, which accumulates in the dermal and epidermal compartments, contributing to the aetiology of photoaging. Strategies to prevent photodamage caused by this cascade of reactions initiated by UV include: prevention of UV penetration into skin by physical and chemical sunscreens, prevention/reduction of inflammation using anti‐inflammatory compounds (e.g. cyclooxygenase inhibitors, inhibitors of cytokine generation); scavenging and quenching of ROS by antioxidants; inhibition of neutrophil elastase activity to prevent extracellular matrix damage and activation of matrix metalloproteases (MMPs), and inhibition of MMP expression (e.g. by retinoids) and activity (e.g. by natural and synthetic inhibitors). Résumé L'inflammation et l'accumulation de dérivés réactifs de l'oxygène qui en résulte jouent un rôle important sur le vieillissement normal (chronologique) et path