Oxidative Damage, Aging and Life Span

描述(由申请人提供)：我们研究的长期目标是了解衰老过程中的分子和遗传因素，并决定寿命。氧化应激假说是解释衰老过程的最重要的假说之一，该假说认为衰老的速度和寿命与细胞器和大分子氧化损伤的积累直接相关。具有不同寿命的物种之间的比较研究一直是氧化应激假说的基础之一，预测氧化损伤的积累、衰老速度和寿命之间存在直接关系。我们建议使用果蝇模型系统，即果蝇黑腹果蝇，利用各种菌株以及已知的改变寿命的环境和遗传条件，比较单一、遗传定义良好的物种中寿命与氧化损伤累积之间的关系。这些研究将更好地定义氧化损伤和寿命之间的精确关系，为详细说明氧化损伤、衰老和寿命之间的具体定量关系奠定基础。用果蝇进行这些比较研究的另一个好处是，果蝇可用的强大的分子和基因技术可以用来直接识别和测试对衰老至关重要的特定生理系统。

DESCRIPTION (provided by applicant): The long-term goal of our studies is to understand the molecular and genetic elements that underlie the process of aging and determine longevity. One of the most prominent hypotheses explaining the aging process is the oxidative stress hypothesis, which states that the rate of aging and life span is directly related to the accumulation of oxidative damage to organelles and macromolecules. Comparative studies between species having different life spans have been one of the foundations of the oxidative stress hypothesis, predicting a direct relationship between the accumulation of oxidative damage, the rate of aging and life span. We propose to use the fruit fly model system, Drosophila melanogaster, to compare the relationship between life span and the accrual of oxidative damage within a single, genetically well defined species, using a variety of strains and environmental and genetic conditions known to alter life span. These studies will better define the precise relationship between oxidative damage and life span, laying the foundation for a map detailing the specific quantitative relationship between oxidative damage, aging and life span. An additional advantage of using Drosophila to perform these comparative studies is that the powerful molecular and genetic techniques available in Drosophila can be used to directly identify and test specific physiological systems important in aging.