No time to sleep on it – start exercising!

Field: Medicine (Health Sciences)

The evolution of technology and 24 h workplaces has seen an increase in population groups reporting inadequate sleep. Inadequate sleep is an emerging risk factor for reduced skeletal muscle mass and sarcopenia, along with several other chronic and metabolic diseases that have discernible links to skeletal muscle health. The maintenance of skeletal muscle mass is dependent upon a fine balance between protein synthesis (anabolism) and protein degradation (catabolism) in the muscle. Rodent studies have previously shown that sleep deprivation decreases muscle fibre cross-sectional area, at the same time as down-regulating markers of protein synthesis and up-regulating markers of protein degradation (de Sa Souza et al. 2016). In this issue of The Journal of Physiology, Saner et al. (2020) are the first to investigate the effect of sleep restriction on skeletal muscle protein synthesis in humans. Twenty-four young, healthy males were randomly grouped and assigned to five consecutive nights of either normal sleep conditions (n = 8), sleep restriction (4 h in bed, n = 8), or sleep restriction and high intensity interval exercise (HIIT) (n = 8). The participants underwent an oral deuterium oxide ingestion protocol. An assessment of myofibrillar protein synthesis (MyoPS), as well as markers of protein synthesis and degradation, was performed on muscle biopsies sampled from the vastus lateralis at baseline, pre- and post-study. The primary finding was that sleep restriction reduced the rate of skeletal muscle MyoPS compared to normal sleep; however, there were no changes in the corresponding markers of protein synthesis and degradation. In addition, it was shown that performing HIIT maintained MyoPS rates similar to that of the normal sleep group, suggesting that HIIT may exert a protective effect on MyoPS. These novel and important findings warrant further discussion regarding mechanisms, clinical outcomes and their applicability to sleep-restricted populations. Sleep restriction alone decreased muscle protein synthesis compared to well-rested participants (Saner et al. 2020), suggesting that inadequate sleep directly impacts muscle protein synthesis rates in males. This finding has significant public health consequences because, in Australia, 40% of the adult population is chronically sleep deprived and one in four workers undertake shiftwork. We previously suggested that sustained changes to wake, work and sleep periods directly and indirectly impair the muscle protein balance via alterations to light exposure, sleep patterns and feeding patterns (Aisbett et al. 2017). A recent pre-print by our group (Lamon et al. 2020) confirms the findings of Saner et al. (2020) and provides further proof-of-concept that one night of total sleep deprivation is sufficient to decrease MyoPS in healthy, young males. Muscle protein synthesis is regulated by a combination of mechanical (muscle contraction), nutritional (dietary protein intake) and hormonal stimuli. Exercise levels and nutritional intake were standardized in the study by Saner et al. (2020), yet hormonal markers were not investigated. Identifying the hormonal changes associated with acute and chronic sleep deprivation may provide essential insights into the mechanisms at play. Experimental evidence exists suggesting that inadequate sleep alters anabolic and catabolic hormone secretion patterns in humans, providing a possible mechanism for impaired muscle protein metabolism (Aisbett et al. 2017). Specifically, the major androgenic hormone testosterone is a potent activator of muscle protein synthesis in males. Sleep restriction alters testosterone secretion patterns, and our recent study suggests that reduced testosterone might constitute a mechanism underlying the sleep restriction-induced decrease in muscle protein synthesis in males (Lamon et al. 2020). If sustained sleep restriction leads to skeletal muscle atrophy over time, it is essential not only to understand the mechanisms by which this occurs, but also how we can blunt this effect. The identification of an intervention that could mitigate the negative consequences of sleep restriction on skeletal muscle health is perhaps the most important clinical outcome of the study by Saner et al. (2020). HIIT performed during the sleep restriction period was able to return MyoPS rates to control levels (Saner et al. 2020). Before such findings guide exercise prescription for sleep-restricted populations, two important factors should be resolved. First, confirming the protective effects of HIIT using a within-participant design in order to fully unpack the sleep-training interaction would be an immediate next step. Second, identifying the best mode of training for protecting skeletal muscle health during periods of sleep restriction would optimize translation into practice. Saner et al. (2020) acknowledge that resistance exercise has been demonstrated as a superior mode of exercise for stimulating skeletal muscle protein synthesis compared to HIIT (Bell et al. 2015). In their study, Bell et al. (2015) provided a direct comparison of the muscle protein synthesis response to resistance exercise, HIIT and continuous aerobic exercise. All protocols were designed at a moderate to high intensity, matched for training volume and completed within a 30 min timeframe, equivalent to the duration used in Saner et al. (2020) and in line with physical activity recommendations. With these protocols, they found resistance exercise to increase muscle protein synthesis rates by ∼25% more compared to HIIT at 24 and 48 h post-exercise (Bell et al. 2015). The metabolic response to exercise is mode specific, with MyoPS being particularly sensitive to mechanical loading. The increased load that is placed on the muscle during resistance exercise triggers an adaptive response, where muscle hypertrophy occurs via accumulated bursts of muscle protein synthesis. By contrast, HIIT or aerobic exercise is typically performed under a lower load and involves different patterns of neurological activation, muscle fibre recruitment and energy expenditure. In their study, Saner et al. (2020) successfully implemented a HIIT protocol of ∼25 min in duration. They rationalized that HIIT constitutes a time-efficient stimulus for inducing skeletal muscle protein synthesis amongst other health benefits, including cardiometabolic advantages that are important for insulin sensitivity and mitochondrial function. In addition to being the exercise mode of choice for stimulating the protein synthesis response, resistance exercise can be implemented in an equally time efficient manner (Bell et al. 2015), with wide ranging health benefits, and may therefore constitute the gold standard strategy for increasing MyoPS in sleep-deprived males. Future research should therefore compare the benefits of HIIT and resistance exercise with respect to attenuating reduced rates of MyoPS caused by sleep restriction. If the clinical relevance of the findings from Saner et al. (2020) are considered important for improvements in the skeletal muscle health of sleep-restricted populations, it is imperative that the applicability of these findings are discussed. Saner et al. (2020) recruited young, untrained males. The ratio of male to female participants is almost two-fold greater in sports and exercise medicine research (Knowles et al. 2019) and possibly greater in sleep research. It is therefore easier to compare results from this specific population group with previous research findings. Untrained participants, however, display a higher muscle protein synthesis response to exercise, which diminishes as the organism adapts to training (Bell et al. 2015). Therefore, if we are to encourage populations experiencing inadequate sleep to perform frequent exercise, it would be valuable to understand the implications for trained individuals. It is therefore important to investigate the implications of sleep restriction not only for both HIIT and resistance exercise MyoPS responses, but also in trained participants. In their discussion, Saner et al. (2020) acknowledge the importance of future research that investigates female populations. Although current research suggests that MyoPS rates are similar between males and females (Knowles et al. 2019), this is an important recommendation from the authors. Females report more sleep problems than males, yet there remains a sparsity of research on female populations in this field. The hormone profile of females may influence the muscle protein response, which is less dependent on testosterone and more dependent on oestrogen and progesterone (Knowles et al. 2019). The menstrual cycle also plays a role in regulating sleep and circadian rhythms. If follows that the combination of these factors likely alters the MyoPS response to exercise under sleep-restricted conditions. The current literature has only investigated MyoPS under normal sleep conditions at two stages of the menstrual cycle, when the ratio of oestrogen to progesterone is small. Oestrogen plays a role in skeletal muscle hypertrophy by stimulating the activation and proliferation of satellite cells and up-regulating the Akt/mTOR pathway, whereas progesterone may have a catabolic effect (Knowles et al. 2019). Growth hormone and Insulin-like growth factor-1 are two other candidate hormones that might take over some of the anabolic effects of testosterone in females. These hormones undergo different patterns of variation across the menstrual cycle, although there is a lack of evidence regarding the impact of sleep restriction on their expression levels, especially in females. Although skeletal muscle hypertrophy is largely determined by the mechanical activation of intracellular signalling pathways, it remains important to understand the impact of the menstrual cycle and other biological sex differences on the interaction between exercise, MyoPS and sleep. Saner et al. (2020) have made a significant step toward understanding the negative health consequences of sleep restriction, with and without preventative exercise intervention. Their findings provide a promising platform for future research that can assist the many populations facing an increased risk of poor health outcomes as a a result of inadequate sleep. No competing interests declared. Sole author. No funding. I would like to acknowledge Dr Séverine Lamon and Associate Professor Brad Aisbett for their insightful feedback on drafts of the manuscript.