Testing Direct Effects of Reproduction on Stress and Mortality via Ovariectomy

描述(申请人提供)：这个项目将研究两种延长蝗虫寿命的实验性治疗方法，如何分配摄取的营养物质，以及细胞是如何维持的。减少饮食摄入量或减少生殖输出的实验操作是延长简单动物寿命的两种最常见的方法。主要假说(即一次性体节假说)表明，减少饮食摄入量和减少生殖输出都是通过将摄取的营养从生殖转移到维持身体来延长寿命的。这改善了人体的细胞维护，从而延长了寿命。尽管这种营养分配假说很流行，但它只经过了一次严格的测试；那次测试缺乏对细胞维持水平的衡量。建议严格跟踪繁殖减少(目标1)或饮食减少(目标2)的蝗虫的摄取营养，并同时测量细胞维持。将通过喂食具有明显非放射性同位素特征的蝗虫饲料来追踪营养物质；如果在觅食后在身体组织中看到这些特征，就是这些摄取的营养物质已经并入体内的证据。细胞维持将通过量化体内细胞中抗氧化酶的活性来衡量。这些酶去除了导致细胞磨损损伤的分子。一次性胞体假说预测，无论是减少生殖还是减少饮食，都会延长寿命，增加摄入的营养到身体的分配(以生殖为代价)，并增强身体这些相同部位的抗氧化活性。 与公共卫生相关：了解饮食限制或减少生殖延长简单动物寿命的内部机制，可能会导致开发其他治疗方法来延长人类的健康年限。减缓老龄化进程本身可以推迟我们社会中主要杀手(例如心脏病、癌症)的发病，并增加人们的健康年数。最后但并非最不重要的一点是，这笔拨款将对北佛罗里达大学的生物学研究环境产生深远的影响，因为它将增加学生研究生物医学科学的机会的质量和数量。

DESCRIPTION (provided by applicant): This project will examine how ingested nutrients are allocated, and cells are maintained, upon two experimental treatments that extend lifespan in grasshoppers. The experimental manipulations of reducing dietary intake or reducing reproductive output are two of the most common means of extending lifespan in simple animals. The predominant hypothesis (viz., the disposable soma hypothesis) suggests that both reducing dietary intake and reducing reproductive output extend lifespan by shifting allotment of ingested nutrients from reproduction to maintaining the body. This results in improved cellular maintenance of the body and thereby longer life. Despite the prevalence of this nutrient allocation hypothesis, it has been rigorously tested only once; that test lacked a measure of the level of cellular maintenance. Rigorous tracking of ingested nutrients in grasshoppers with reduced reproduction (Aim #1) or reduced diet (Aim #2), and simultaneously measurement of cellular maintenance are proposed. Nutrients will be tracked by feeding grasshoppers diets that have distinct non-radioactive isotopic signatures; if these signatures are seen in body tissues after feeding, it is evidence that these ingested nutrients have been incorporated into the body. Cellular maintenance will be measured by quantifying the activity of anti-oxidant enzymes in body cells. These enzymes remove molecules that cause wear-and-tear damage in cells. The disposable soma hypothesis predicts that either reduced reproduction or reduced diet will increase lifespan, increase allocation of ingested nutrients to the body (at the expense of reproduction), and increase anti-oxidant activity in those same parts of the body. PUBLIC HEALTH RELEVANCE: Understanding the internal mechanisms by which dietary restriction or reduced reproduction extend lifespan in simple animals may lead to development of other treatments to extend the healthy years of people. Slowing the aging process itself could delay the onset of the major killers in our society (e.g., heart disease, cancer) and increase the number of healthy years for people. Last but not least, this grant will have a profound effect on the research environment in biology at the University of North Florida, by increasing the quality and quantity of opportunites for student research in biomedical science.