Activation of transcription factor nrf2 by isothiocyanates and prevention of cellular senescence in vitro

变老会对我们的皮肤、组织和整体健康造成持续的损害。对衰老过程的了解和适当的药物或营养补充剂来减缓这一过程可能会帮助我们在老年时更健康。对蛋白质和DNA的自发损伤在细胞的生命过程中积累，并导致衰老效应。这可能可以通过增加保护蛋白质和DNA免受损害的酶的活性来抵抗。乙草酸酶I(GLO1)就是一种这样的酶。GLO1直接保护蛋白质和DNA免受活性糖类分子的损伤，间接保护细胞免受氧化损伤和呼吸损伤。通过在实验条件下过度表达GLO1基因来增加GLO1的数量，最近被证明可以使一种通常被用作衰老实验模型的小蠕虫(线虫)的寿命延长40%。我最近发现，从卷心菜、花椰菜和其他蔬菜中吸收的化合物也可以增加GLO1。这些化合物，异硫氰酸酯，激活影响GLO1基因调控的过程。我认为异硫氰酸酯极有可能通过增加GLO1的表达来减缓衰老过程，可能还有其他影响。为了测试这一点，在这个项目中，我将使用衰老的人类细胞培养模型。我将测试通过基因技术实现的GLO1的过度表达是否可以防止人类细胞衰老/测量对蛋白质和DNA的预期损害减少。然后，我将看看这是否也可以通过异硫氰酸酯诱导GLO1基因的表达来实现。一个成功的结果将给出第一个建议，吃你的蔬菜可能会减缓衰老过程。

Growing old takes a continuing toll on our skin, tissues and general health. An understanding of the ageing process and appropriate drugs or nutritional supplements to slow the process down may help us be healthier in old age. Spontaneous damage to proteins and DNA accumulates in cells during their life and contributes to the ageing effects. This can probably be resisted by increasing the activity of enzymes that protect proteins and DNA from damage. One such enzyme is glyoxalase I (GLO1). GLO1 protects proteins and DNA directly against damage from reactive sugar-derived molecules and protects indirectly against oxidative damage and impairment of cell respiration. Increasing the amount of GLO1, by overexpression of the gene for GLO1 in experimental conditions, has recently been shown to produce a 40% increase in lifespan of a small worm (nematode) commonly used as an experimental model of ageing. I have recently found that GLO1 can also be increased by compounds absorbed from Brassica vegetables such as cabbage, broccoli and others. These compounds, isothiocyanates, activate processes that affect the regulation of the GLO1 gene. I think it highly likely that isothiocyanates may slow the ageing process by increasing GLO1 expression / with probably also other effects. To test this, in this project I will use a human cell culture model of ageing. I will test if overexpression of GLO1 achieved by genetic techniques prevents ageing of human cells / measuring the expected decrease in damage to protein and DNA. I will then see and if this can also be achieved by induction of GLO1 gene expression by isothiocyanates. A successful outcome will give the first suggestions that eating your greens may slow the ageing process.