Pathophysiological mechanisms of reduced physical activity: Insights from the human step reduction model and animal analogues

Abstract

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.

The effect of sedentary time on cardiovascular disease risk in middle-aged and elderly patients with type 2 diabetes mellitus

“…[ 20 ] A study on animals also confirmed that sedentary rats had decreased fatty acid oxidation ability and increased fat mass, and the fat mass increase rate of older rats was higher. [ 23 ] This makes a mechanism contribution to the increase of CVD risk. In addition, sedentary time has been shown to be associated with inflammatory markers (C-reactive protein).…”

Muscle physiology and its relations to the whole body in health and disease

“…They also summarize validations that exercise can counteract the negative effects. 21 Exercise puts muscle tissue into stress. Particularly, the endoplasmic reticulum (ER) undergoes stress-related adaptations.…”

“…In particular, decrements in 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. They also summarize validations that exercise can counteract the negative effects 21 …”

Plasticity

“…recently developed a deep learning–based platform for an in‐depth, automated fiber and nucleus type analysis, to significantly improve the characterization of affected muscle fibers in, for example, degenerative disease [reviewed in 9]. In turn, organelle plasticity also mediates the downside of exercise adaptation, that is, the negative, pathophysiological mechanisms of a reduction in physical activity 10 …”