UF PASS: Regulation of exercise transducers

摘要运动是一种强大而多效的生理刺激，有助于预防许多慢性疾病 治疗疾病的药物，用于治疗疾病。虽然锻炼的有益效果广泛 承认，关于分子换能器对整个系统的影响，人们仍然知之甚少。 这所佛罗里达大学的目标是进行体力活动分子传感器的临床前动物研究 现场应用(UF PASS)是在动物身上进行实验，提供组织/血液(即 生物谱系)到化学分析部位，用于鉴定Defined诱导的分子换能器 无法从人类获得的组织中的身体活动模型以及进行 可以支持筛选新型换能器的机械研究，以快速推动该领域的发展。 在第一阶段，UF PASS建议在耐力之后为化学分析站点收集生物标本 雄性和雌性Fischer 344xBrown挪威大鼠(F344-BN)的跑步训练或阻力运动方案 在三个不同的年龄。为了更好地捕捉运动/适应反应的动态，我们建议： 1)在幼稚和训练有素的大鼠进行一次急性运动后，在选定的5个时间点收集生物样品； 2)在短期训练(5个回合之后)后收集生物样本；3)收集以下生物样本 长期(8周)训练。 对于第二阶段，我们的假设是从肌肉中释放的因子(即肌动蛋白)是分子传导器 这在整个系统中发挥作用，以提高公认的压力耐受性。这些研究的目标是 将使用高通量筛选技术测试多达1500个肌动蛋白。然后我们将使用 二次筛选技术测试100名候选人，我们将从其中选择最多3名候选人进行体内试验 测试。AIM 3中的实验结果将提供识别一组换能器的分子证据， 从肌肉中释放出来，对运动诱导的全身健康是必要的。UF PASS的目标将是 具体目标有以下几点： 具体目标1：中心协调阶段。 具体目标2：第一阶段研究。用男和女进行耐力和耐力练习 F344BN大鼠在3-4、16-18、27-29个月。 具体目标3：第二阶段研究。目标3中的目标是测试肌肉激动素作为运动转导 提高了对压力的耐受力。

Abstract Exercise is a powerful and pleiotropic physiological stimulus that helps prevent many chronic diseases and is used as a therapeutic for disease. While the beneficial effects of exercise are extensively acknowledged there is still very little understood about the molecular transducers of the systems-wide effects. The goal of this University of Florida Molecular Transducers of Physical Activity Preclinical Animal Study Sites application (UF PASS) is to conduct experiments in animals that will provide tissues/blood (i.e. biospecimens) to the Chemical Analysis Sites for identification of molecular transducers induced by defined models of physical activity from tissues that cannot be obtained from humans as well as to conduct mechanistic studies that can support screening of novel transducers to quickly move the field forward. In Phase 1, UF PASS proposes to collect biospecimens for the Chemical Analysis sites following endurance (run-training) or resistance exercise protocols on male and female Fischer 344xBrown Norway rats (F344-BN) at three different ages. To better capture the dynamics of the exercise/adaptation responses we propose to: 1) Collect biospecimens at 5 selected timepoints following an acute bout of exercise on naïve and trained rats; 2) Collect biospecimens following short duration training (after 5 bouts) and 3) Collect biospecimens following long-term (8 weeks) training. For Phase 2, our hypothesis is that factors released from muscle (i.e. myokines) are the molecular transducers that function throughout the system to improve the well-established stress tolerance. The goal of these studies will be to employ high throughput screening technologies to test up to 1500 myokines. We will then use secondary screening techniques to test 100 candidates from which we will select up to 3 candidates for in vivo testing. The results of the experiments in Aim 3 will provide molecular evidence identifying a set of transducers, released from muscle, that are necessary for exercise induced systemic health. The goals of the UF PASS will be pursued by the following Specific Aims: Specific Aim 1: Center Coordination Phase. Specific Aim 2: Phase 1 Studies. To perform endurance and resistance exercise using male and female F344BN rats at 3-4, 16-18, and 27-29 mo. Specific Aim 3: Phase 2 Studies. The goal in Aim 3 is to test myokines as the exercise transducers for improved stress tolerance.