Tinkerhess Martin J, Ginzberg Sara, Piazza Nicole, Wessells Robert J
Department of Geriatric Medicine, University of Michigan Medical School, Michigan, USA.
J Vis Exp. 2012 Mar 26(61):3786. doi: 10.3791/3786.
One of the most pressing problems facing modern medical researchers is the surging levels of obesity, with the consequent increase in associated disorders such as diabetes and cardiovascular disease (1-3). An important topic of research into these associated health problems involves the role of endurance exercise as a beneficial intervention. Exercise training is an inexpensive, non-invasive intervention with several beneficial results, including reduction in excess body fat (4), increased insulin sensitivity in skeletal muscle (5), increased anti-inflammatory and antioxidative responses (6), and improved contractile capacity in cardiomyocytes (7). Low intensity exercise is known to increase mitochondrial activity and biogenesis in humans (8) and mice, with the transcriptional coactivator PGC1-α as an important intermediate (9,10). Despite the importance of exercise as a tool for combating several important age-related diseases, extensive longitudinal genetic studies have been impeded by the lack of an endurance training protocol for a short-lived genetic model species. The variety of genetic tools available for use with Drosophila, together with its short lifespan and inexpensive maintenance, make it an appealing model for further study of these genetic mechanisms. With this in mind we have developed a novel apparatus, known as the Power Tower, for large scale exercise-training in Drosophila melanogaster (11). The Power Tower utilizes the flies' instinctive negative geotaxis behavior to repetitively induce rapid climbing. Each time the machine lifts, then drops, the platform of flies, the flies are induced to climb. Flies continue to respond as long as the machine is in operation or until they become too fatigued to respond. Thus, the researcher can use this machine to provide simultaneous training to large numbers of age-matched and genetically identical flies. Additionally, we describe associated assays useful to track longitudinal progress of fly cohorts during training.
现代医学研究人员面临的最紧迫问题之一是肥胖水平的飙升，以及随之而来的糖尿病和心血管疾病等相关疾病的增加(1-3)。对这些相关健康问题的一个重要研究课题涉及耐力运动作为一种有益干预措施的作用。运动训练是一种廉价、非侵入性的干预措施，有几个有益的效果，包括减少多余的体脂(4)、增加骨骼肌的胰岛素敏感性(5)、增加抗炎和抗氧化反应(6)以及改善心肌细胞的收缩能力(7)。已知低强度运动可增加人类(8)和小鼠的线粒体活性和生物发生，转录共激活因子PGC1-α是一个重要的中间体(9,10)。尽管运动作为对抗几种重要的与年龄相关疾病的工具很重要，但由于缺乏针对短命遗传模型物种的耐力训练方案，广泛的纵向遗传研究受到了阻碍。可用于果蝇的各种遗传工具，加上其短寿命和低成本维护，使其成为进一步研究这些遗传机制的有吸引力的模型。考虑到这一点，我们开发了一种新颖的仪器，称为动力塔，用于黑腹果蝇的大规模运动训练(11)。动力塔利用果蝇天生的负趋地性行为来反复诱导快速攀爬。每次机器抬起然后放下果蝇平台时，果蝇都会被诱导攀爬。只要机器在运行，果蝇就会继续做出反应，直到它们变得过于疲劳而无法做出反应。因此，研究人员可以使用这台机器对大量年龄匹配且基因相同的果蝇进行同步训练。此外，我们还描述了有助于跟踪训练期间果蝇群体纵向进展的相关检测方法。
