Testing Direct Effects of Reproduction on Stress and Mortality via Ovariectomy

描述（由申请人提供）：本项目将通过两种延长蚱蜢寿命的实验处理，研究摄入的营养物质是如何分配的，细胞是如何维持的。在简单动物中，减少饮食摄入或减少繁殖是延长寿命的两种最常见的方法。占主导地位的假说（即一次性躯体假说）认为，减少饮食摄入和减少生殖产出都可以通过将摄入的营养从生殖转移到维持身体来延长寿命。这可以改善身体的细胞维护，从而延长寿命。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；该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）的蚱蜢摄入的营养物质，并同时测量细胞维持。通过给蚱蜢喂食具有明显非放射性同位素特征的食物来追踪营养；如果在进食后在身体组织中看到这些特征，则证明这些摄入的营养物质已被纳入体内。细胞维持将通过量化体内细胞中抗氧化酶的活性来衡量。这些酶可以去除导致细胞磨损的分子。一次性躯体假说预测，减少生殖或减少饮食都会延长寿命，增加摄入的营养分配给身体（以牺牲生殖为代价），并增加身体相同部位的抗氧化活性。

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.