Homo sapiens May Incorporate Daily Acute Cycles of "Conditioning-Deconditioning" to Maintain Musculoskeletal Integrity: Need to Integrate with Biological Clocks and Circadian Rhythm Mediators

Abstract

Human evolution required adaptation to the boundary conditions of Earth, including 1 g gravity. The bipedal mobility of Homo sapiens in that gravitational field causes ground reaction force (GRF) loading of their lower extremities, influencing the integrity of the tissues of those extremities. However, humans usually experience such loading during the day and then a period of relative unloading at night. Many studies have indicated that loading of tissues and cells of the musculoskeletal (MSK) system can inhibit their responses to biological mediators such as cytokines and growth factors. Such findings raise the possibility that humans use such cycles of acute conditioning and deconditioning of the cells and tissues of the MSK system to elaborate critical mediators and responsiveness in parallel with these cycles, particularly involving GRF loading. However, humans also experience circadian rhythms with the levels of a number of mediators influenced by day/night cycles, as well as various levels of biological clocks. Thus, if responsiveness to MSK-generated mediators also occurs during the unloaded part of the daily cycle, that response must be integrated with circadian variations as well. Furthermore, it is also possible that responsiveness to circadian rhythm mediators may be regulated by MSK tissue loading. This review will examine evidence for the above scenario and postulate how interactions could be both regulated and studied, and how extension of the acute cycles biased towards deconditioning could lead to loss of tissue integrity.

Keywords: acute conditioning; acute deconditioning; circadian rhythms; connective tissue homeostasis; ground reaction forces; myokines; osteokines.

Figure 1

Melatonin variation in plasma over a 24 h period—drawn from data reported in Dijk et al. [5] for seven 21–25 year old males, presented as Z-scores to reduce variability.

Figure 2

Data for the cytokine IL-6 as reported in Steensberg et al. [26] are plotted (Running data); the data were obtained from seven male endurance trained runners aged 24–50 years who ran on a treadmill at 75% VO2 max for 2.5 h, having reported to the lab at 0800. The sclerostin (osteokine) data (solid squares and diamonds) are—as reported in Nelson et al. [27]—acquired from 20 pre-menopausal and 20 post-menopausal women who arrived at the lab between 0800 and 0900, were provided a specified breakfast and then did a series of jumping exercises before blood samples were taken. Baseline data for these latter two groups are zero on that scale.

Figure 3

Schematic of the potential effects of loading on the MSK system and how this might require integration of exercise/loading-associated mediators (myokines and osteokines) with mediators following a circadian pattern.