Prevention of cutaneous photoageing by dietary antioxid*

描述（由申请人提供） 皮肤老化是一种复杂的生物学现象，由两种不同的 组成部分：（1）内在的，遗传决定的退行性老化 过程，以及（2）由于暴露于环境而引起的外在老化， 特别是太阳紫外（UV）光，也称为光老化。 暴露 紫外线辐射，特别是UVB（290-320纳米）对哺乳动物皮肤的影响， 导致包括光老化在内的几种皮肤疾病， 最危险的环境污染物。 有充分的证据表明， 辐射是活性氧（ROS）的有效生产者，其中有2 潜在的重要影响：损害各种细胞成分， 触发特定信号通路的激活。 这两 影响与年龄相关的皮肤的许多细胞过程 包括光老化在内的疾病。 一个切实可行的办法，以减少风险 紫外线诱导的ROS介导的皮肤光老化可能是使用膳食植物 具有抗氧化特性的补充剂。 在早期的研究中， 研究者已经表明，绿色茶多酚（以下称为 GTP）对紫外线诱导的氧化应激具有显著的预防作用， 皮肤 本提案中要检验的中心假设是， 体内UVB暴露于皮肤耗尽抗氧化防御系统并诱导 氧化应激，导致细胞外信号调节的激活， 激酶、c-Jun氨基末端激酶和p38丝裂原活化蛋白激酶 （MAPK）信号通路。 MAPK的激活导致磷酸化 转录因子，这反过来又导致上调 金属蛋白酶（MMP）的作用，并导致皮肤的光老化。 的推论 假设是，饮食中的抗氧化剂补充剂，如GTP， SKH-1无毛小鼠饮水可预防UVB辐射诱发 抗氧化防御系统和氧化应激的耗竭，因此 氧化应激介导的MAPK信号通路的磷酸化。 的 抑制UVB诱导的氧化应激介导的 GTP在体内的细胞信号传导将导致皮肤光老化的减少 发病率。 验证这一假设将对以下方面产生重大影响： 氧化应激介导的皮肤老化的重要性，以及提供 发展新的干预方法和战略， 通过使用膳食抗氧化剂补充剂防止皮肤光老化。

DESCRIPTION (provided by applicant) 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.