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现象，由两种截然不同的 组成部分：(1)由基因决定的固有退行性衰老 过程，以及(2)暴露在环境中的外在老化， 特别是太阳紫外线(UV)，也称为光老化。暴露量 对哺乳动物皮肤的紫外线辐射，特别是UVB(290-320纳米) 对包括光老化在内的几种皮肤疾病负责，因此使它 危害最大的环境污染物。有充分的证据表明，紫外线 辐射是一种有效的产生活性氧物种(ROS)的物质，它有2 潜在的重要影响：各种细胞成分和 触发特定信号通路的激活。这两个都是 效应可影响与年龄相关的皮肤相关的许多细胞过程 包括光老化在内的疾病。一种降低风险的实用方法 紫外线诱导的ROS介导的皮肤光老化可能是饮食植物学的使用 具有抗氧化性的补充剂。在早期的研究中， 调查表明，绿茶多酚(以下简称绿茶) GTP)对紫外线诱导的小鼠氧化应激有显著的预防作用 皮肤。这项提案中要检验的中心假设是，在 体内中波紫外线暴露皮肤耗尽抗氧化防御系统并诱导 氧化应激，导致激活细胞外信号调节 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，进而导致转录因子上调 金属蛋白酶(MMPs)，并导致皮肤光老化。推论 假设是膳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 抗氧化防御系统的耗尽和氧化应激，从而 氧化应激介导的MAPK信号通路的磷酸化。这个 抑制中波紫外线诱导的氧化应激介导的磷酸化 GTP体内细胞信号转导可减少皮肤光老化 发病率。这一假说的验证将对 氧化应激介导的皮肤老化的重要性，以及提供 承诺开发新的干预方法和战略，以 通过使用饮食中的抗氧化剂补充剂来防止皮肤光老化。

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.