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和决定长寿的分子和遗传因素。解释衰老过程的最突出的假说之一是氧化应激假说，该假说指出衰老和寿命的速度与细胞器和大分子的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的直接关系。我们建议使用果蝇模型系统，黑腹果蝇，比较寿命和累积的氧化损伤之间的关系在一个单一的，遗传定义明确的物种，使用各种菌株和环境和遗传条件，已知改变寿命。这些研究将更好地定义氧化损伤和寿命之间的精确关系，为绘制一张详细描述氧化损伤、衰老和寿命之间具体定量关系的地图奠定基础。使用果蝇进行这些比较研究的另一个优点是，果蝇中强大的分子和遗传技术可用于直接识别和测试衰老中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.