Department of Biomedical Sciences, University of Padova, Padova, Italy.
Department of Molecular Medicine, Institute of Physiology, University of Pavia, Pavia, Italy.
Acta Physiol (Oxf). 2023 Jul;238(3):e13986. doi: 10.1111/apha.13986. Epub 2023 May 22.
Physical inactivity represents a heavy burden for modern societies and is spreading worldwide, it is a recognised pandemic and is the fourth cause of global mortality. Not surprisingly, there is an increasing interest in longitudinal studies on the impact of reduced physical activity on different physiological systems. This narrative review focuses on the pathophysiological mechanisms of step reduction (SR), an experimental paradigm that involves a sudden decrease in participants' habitual daily steps to a lower level, mimicking the effects of a sedentary lifestyle. Analogous animal models of reduced physical activity, namely, the "wheel-lock" and the "cage reduction" models, which can provide the foundation for human studies, are also discussed. The empirical evidence obtained thus far shows that even brief periods of reduced physical activity can lead to substantial alterations in skeletal muscle health and metabolic function. In particular, decrements in lean/muscle mass, muscle function, muscle protein synthesis, cardiorespiratory fitness, endothelial function and insulin sensitivity, together with an increased fat mass and inflammation, have been observed. Exercise interventions seem particularly effective for counteracting these pathophysiological alterations induced by periods of reduced physical activity. A direct comparison of SR with other human models of unloading, such as bed rest and lower limb suspension/immobilisation, is presented. In addition, we propose a conceptual framework aiming to unravel the mechanisms of muscle atrophy and insulin resistance in the specific context of reduced ambulatory activity. Finally, methodological considerations, knowledge gaps and future directions for both animal and human models are also discussed in the review.
身体活动不足是现代社会的沉重负担，正在在全球范围内蔓延，它是一种公认的大流行病，是全球死亡的第四大原因。毫不奇怪，人们对减少身体活动对不同生理系统影响的纵向研究越来越感兴趣。本综述重点介绍了步速降低（SR）的病理生理机制，这是一种实验范式，涉及参与者习惯性日常步数突然降低到较低水平，模拟久坐生活方式的影响。类似的减少身体活动的动物模型，即“轮锁”和“笼式减少”模型，也可以为人类研究提供基础，也进行了讨论。迄今为止获得的经验证据表明，即使是短暂的身体活动减少也会导致骨骼肌健康和代谢功能的实质性改变。具体而言，已经观察到瘦/肌肉质量、肌肉功能、肌肉蛋白合成、心肺功能、内皮功能和胰岛素敏感性的降低，以及脂肪质量和炎症的增加。运动干预似乎特别有效地对抗由身体活动减少引起的这些病理生理改变。对 SR 与其他人类减载模型（如卧床休息和下肢悬吊/固定）进行了直接比较。此外，我们提出了一个概念框架，旨在揭示在减少活动能力的特定背景下肌肉萎缩和胰岛素抵抗的机制。最后，还讨论了动物和人类模型的方法学考虑、知识空白和未来方向。
