An intriguing observation was that 84 days of bed rest induced alterations in several genes and transcription factors involved in circadian rhythm regulation. Muscle activity and nutrient intake are known cues for the circadian rhythm regulation in skeletal muscle.
50,
51 Given that diet and time of meals were controlled for in the current study, and the observed differences between bed rest with vs without exercise (see below), our results support the idea of a disuse‐sensitive circadian molecular clock in the skeletal muscle.
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54
These findings add information from in vivo human muscle to past reports describing atypical expression of core clock genes/transcription factors after muscle denervation in mice.
55 The Bmal1‐CLOCK complex is the central modulator of the circadian rhythm system. In the current study, the antagonistic factors RORA and NR1D2 were both upregulated after long‐term bed rest, which may be related to a myocellular effort to stabilize the regulatory feedback loop controlling Bmal1 expression, and thus, decrease the impact of the lack of mechanical stimuli on circadian rhythms regulation.
The implications of the unloading‐induced circadian rhythm alterations reported here should not be overlooked, since the cell‐autonomous skeletal muscle clocks have been shown to impact important pathways involved in human skeletal muscle remodeling, and to be essential for proper insulin handling, lipic homeostasis, and myokine secretion
