Power Tower: A Novel Paradigm for Exercsie Training in Drosophila melanogaster

描述（由申请人提供）：近年来，耐力运动已经成为一种能够改善人类和脊椎动物模型中各种健康参数的有效干预措施。虽然已经了解了很多关于脊椎动物对运动训练的生理反应，但这些反应所需的遗传成分仍然没有得到很好的理解。考虑到这一点，我们已经开发了一种新的耐力运动模型，在遗传上易于处理的研究有机体，果蝇。多种基因型的果蝇通过提高攀爬能力和心脏抗应激能力以及增加线粒体活性来响应耐力运动计划，这表明运动在无脊椎动物中产生与脊椎动物相似的效果。然而，为了充分建立该模型系统的实用性，首先需要更充分地表征果蝇和脊椎动物运动反应之间的相似性和差异。在这里，我们建议建立相关的苍蝇作为一个运动模型，通过表征各种生理反应的苍蝇模型中的运动。其次，我们建议通过测试已知在调节脊椎动物生理学中对苍蝇运动反应的影响很重要的候选基因来建立这些反应中涉及的遗传途径的保守性。一旦确定了苍蝇作为运动模型的相关性，苍蝇遗传学的力量就可以用来发现能够调节或模拟脊椎动物运动反应的新型保守遗传因子。 公共卫生相关性：了解运动生理学的遗传机制与美国国立卫生研究院和国家心肺血液研究所的使命有关，因为识别反应的关键遗传成分将允许设计退行性肌肉疾病和与年龄相关的肌肉功能下降的治疗和预防方案。

DESCRIPTION (provided by applicant): Endurance exercise has emerged in recent years as a potent intervention capable of improving a wide variety of health parameters in humans and in vertebrate models. Although much has been learned about physiological responses to exercise training in vertebrates, the genetic components necessary for these responses are still not well understood. With this in mind, we have developed a novel endurance exercise model in a genetically tractable research organism, the fruit fly. Flies of multiple genotypes respond to a program of endurance exercise by improving climbing ability and cardiac stress resistance, as well as increasing mitochondrial activity, suggesting that exercise produces similar effects in invertebrates as in vertebrates. In order to fully establish the utility of this model system, however, it will first be necessary to more fully characterize the similarities and differences between the exercise response in flies and in vertebrates. Here, we propose to establish the relevance of flies as an exercise model by characterizing a variety of physiological responses to exercise in the fly model. Secondly, we propose to establish conservation of genetic pathways involved in these responses by testing candidate genes known to be important in regulating vertebrate physiology for their effects on the exercise response of the fly. Once the relevance of flies as an exercise model is established, the power of fly genetics can be used to uncover novel conserved genetic factors capable of regulating or mimicking the exercise response in vertebrates. PUBLIC HEALTH RELEVANCE: Understanding genetic mechanisms of exercise physiology is relevant to the mission of the National Institutes of Health and the National Heart Lung and Blood Institute because the identification of key genetic components of the response will allow design of treatments and prevention programs for degenerative muscular diseases and age-related decline in muscular function.