Mimicking exercise: what matters most and where to next?
Mimicking exercise: what matters most and where to next?
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DOI：
10.1113/jp278761
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Green DJ
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文献类型：
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作者：
Hawley JA;Joyner MJ;Green DJ
在过去的十年中，人们对识别模拟或增强运动效果的生物活性口服化合物（即所谓的“运动药丸”或“运动模拟物”）的科学和商业兴趣越来越大。迄今为止，这些化合物通常以骨骼肌为目标，试图刺激耐力训练诱导的运动适应性。因此，它们不能赋予在骨骼肌以外的组织和器官中看到的运动的许多广泛的健康保护作用。在这种背景下，多个整合的监管和往往冗余的途径已经发展到检测和响应人类运动，在这里，我们考虑设计一种药丸，可能模仿广泛的运动益处的复杂挑战。特别是，我们考虑到运动对动脉粥样硬化和心血管系统的广泛影响，目前的“肌中心”范式的局限性。我们讨论的有效性和局限性的概念，低剂量的心血管polypills，已经在大规模的试验中，可能代表一种形式的心血管运动模拟。最后，鉴于一些对运动药丸的呼吁源于对专家建议，循证指南和当前公共卫生方法的失败的回应，我们探讨了可能解决全球不活动增加的可能策略。在一个广谱运动模拟可能会被开发的情况下，我们讨论了一些通用的问题，通过和坚持治疗干预措施。 自愿的、动态的运动引起多个组织和器官的广泛扰动（左）。为了模拟运动训练的效果，化合物专注于选定的骨骼肌信号通路（右），忽略了运动对其他器官和组织（如心脏）的许多健康保护作用。
The past decade has witnessed growing scientific and commercial interest in the identification of bioactive oral compounds that mimic or potentiate the effects of exercise, so‐called ‘exercise pills’ or ‘exercise mimetics.’ These compounds have, to date, typically targeted skeletal muscle in an attempt to stimulate some of the adaptations to exercise induced by endurance training. Accordingly, they fail to impart many of the broad health protecting effects of exercise that are seen in tissues and organs other than skeletal muscle. In the context that multiple integrative regulatory and often redundant pathways have evolved to detect and respond to human movement, here we consider the complex challenges of designing a pill that might mimic the extensive range of exercise benefits. In particular, we consider the limits of the current ‘myocentric’ paradigm given the wide‐ranging array of impacts that exercise exerts on atherosclerosis and the cardiovascular system. We discuss the validity and limitations of the concept that low dose cardiovascular polypills, already in large scale trials, may represent one form of cardiovascular exercise mimetic. Finally, given that some calls for an exercise pill stem from a response to the perceived failure of expert advice, evidence‐based guidelines and current public health approaches, we explore possible strategies that might address the global rise in inactivity. In the event that a broad spectrum exercise mimetic might ever be developed, we discuss some generic issues related to adoption and adherence of therapeutic interventions. Abstract figure legend Voluntary, dynamic exercise provokes widespread perturbations in multiple tissues and organs (left). In an attempt to mimic the effects of exercise training, compounds have focused on selected skeletal muscle signalling pathways (right), ignoring many of the health‐protecting effects of exercise in other organs and tissues, such as the heart.