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

描述（由申请人提供）：耐力运动近年来作为一种有效的干预措施出现，能够改善人类和脊椎动物模型的各种健康参数。尽管人们对脊椎动物对运动训练的生理反应已经了解了很多，但对这些反应所必需的遗传成分仍然没有很好地了解。考虑到这一点，我们开发了一种新的耐力运动模型，在一种遗传上易于处理的研究生物中，果蝇。多种基因型的果蝇通过提高攀爬能力和心脏抗逆性，以及增加线粒体活性来对耐力运动做出反应，这表明运动对无脊椎动物和脊椎动物产生相似的影响。然而，为了充分建立该模型系统的效用，首先有必要更充分地表征果蝇和脊椎动物运动反应之间的异同。在这里，我们建议通过表征果蝇模型中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来建立参与这些反应的遗传途径的保护，以了解它们对果蝇运动反应的影响。一旦建立了果蝇作为运动模型的相关性，果蝇遗传学的力量就可以用来揭示能够调节或模仿脊椎动物运动反应的新的保守遗传因素。

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.