Cutaneous ageing is a complex biological phenomenon consisting of 2 distinct components: (1) the intrinsic, genetically-determined degenerative ageing processes, and (2) extrinsic ageing due to exposure to the environment, paticularly solar ultraviolet (UV) light, also known as photoageing. Exposure of UV radiation, particularly UVB (290-320 nanometers), to mammalian skin is responsible for several skin disorders including photoageing, thus making it the most hazardous environmental pollutant. It is well documented that UV radiation is a potent producer of reactive oxygen species (ROS), which have 2 potentially important effects: damage of various cell components and triggering the activation of specific signaling pathways. Both of these effects can influence numerous cellular processes linked to age-related skin diseases including photoageing. One practical approach to reduce the risk of UV-induced ROS-mediated skin photoageing may be the use of dietary botanical supplements having antioxidant properties. In earlier studies, the investigators have shown that green tea polyphenols (hereafter referred as GTP) have remarkable preventive effects against UV-induced oxidative stress in the skin. The central hypothesis to be tested in this proposal is that in vivo UVB exposure to skin depletes antioxidant defense system and induces oxidative stress, which causes activation of extracellular signal-regulated kinase, c-Jun amino-terminal kinase and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Activation of MAPK results in phosphorylation of the transcription factors, which in turn results in upregulation of metalloproteinases (MMP) and leads to photoageing of the skin. The corollary to the hypothesis is that dietary antioxidant supplements such as GTP in drinking water to SKH-1 hairless mice will prevent UVB radiation-induced depletion of antioxidant defense system and oxidative stress, and thus oxidative stress-mediated phosphorylation of MAPK signaling pathways. The inhibition of UVB-induced oxidative stress-mediated phosphorylation of cellular signaling in vivo by GTP will result in reduction of skin photoageing incidence. Validation of this hypothesis would have major implications for the importance of oxidative stress-mediated skin ageing, as well as offering promise for the development of novel intervention approaches and strategies to prevent skin photoageing by the use of dietary antioxidant supplements.
