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

描述(由申请人提供)：近年来，耐力锻炼已成为一种有效的干预措施，能够改善人类和脊椎动物模型中的各种健康参数。虽然关于脊椎动物对运动训练的生理反应已经有了很多了解，但这些反应所必需的遗传成分仍然没有被很好地理解。考虑到这一点，我们在一种遗传上易驯化的研究生物--果蝇--中开发了一种新的耐力运动模型。多种基因类型的果蝇对耐力运动的反应是通过提高攀爬能力和心脏应激能力，以及增加线粒体活性，这表明运动在无脊椎动物身上产生的效果与脊椎动物相似。然而，为了充分建立这个模型系统的实用性，首先有必要更充分地描述苍蝇和脊椎动物运动反应之间的相似和不同。在这里，我们建议通过在果蝇模型中表征对运动的各种生理反应来建立果蝇作为运动模型的相关性。其次，我们建议通过测试已知在调节脊椎动物生理学中重要的候选基因对苍蝇运动反应的影响，来建立参与这些反应的遗传路径的保守性。一旦建立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仿脊椎动物运动反应的新的保守遗传因素。 公共卫生相关性：了解运动生理学的遗传机制与国家卫生研究院和国家心肺血液研究所的使命相关，因为确定反应的关键遗传成分将有助于设计针对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计划。

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.