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

Abstract

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).

Cosmeceuticals Derived from Bioactive Substances Found in Marine Algae

“…Fucosterol can help in cellular defense mechanisms by preventing cell membrane oxidation as it has an important role in scavenging hydrogen peroxide and restoring SOD activity. Similarly, an increase in GSH-px activity indicates that fucosterol also helps in the restoration of vital endogenous antioxidants such as gluthathione [11,13].…”

“…The most important non-enzymatic antioxidants are vitamins C and E, β-carotene and coenzyme Q10 (ubiquinone, ubidecarenone) [13]. Extrinsic environmental effects such as UV irradiation initiate and activate a complex cascade of biochemical reactions in human skin causing depletion of these enzymes.…”

“…ROS have a major role in photo-aging of human skin in vivo [13][14][15], by causing oxidative damage to cellular DNA, proteins, membrane lipids and carbohydrates, which accumulate in the dermal and epidermal compartments. Photo oxidative damage is the result of UV irradiation due to the generation of ROS [16].…”

“…MMPs are major enzymes involved in the remodeling of the extracellular matrix by proteolytic degradation of collagen and elastic fibres, resulting in the loss of the skin's ability to resist stretching. In normal skin, MMPs are expressed in very low levels and are kept inactive [13].…”

“…Chronically UV irradiated skin is associated with abnormal cutaneous reactions such as epidermal hyperplasia, accelerated breakdown of collagen, and inflammatory responses. The effect of UV radiation has a strong oxidative component and photo-oxidative stress has been directly linked to the onset of skin photodamage [51]. Hence, regular skin treatment with products containing antioxidant ingredients is thought be a useful strategy for preventing/reducing UV induced damage (Figure 5a).…”