The interactive effect of sustained sleep restriction and resistance exercise on skeletal muscle transcriptomics in young females.

INTRODUCTION: Both sleep loss and exercise regulate gene expression in skeletal muscle, yet little is known about how the interaction of these stressors affects the muscle transcriptome. The aim of this study was to investigate the effect of nine nights of sleep restriction, with repeated resistance exercise (REx) sessions, on the skeletal muscle transcriptome of young, trained females. METHODS: Ten healthy females aged 18-35 years undertook a randomised cross-over study of nine nights' sleep restriction (SR; 5-h time in bed) and normal sleep (NS; ≥7 h time in bed) with a minimum 6-week washout. Participants completed four REx sessions per condition (day 3, 5, 7 and 9). Muscle biopsies were collected both pre- and post-REx on days 3 and 9. Gene and protein expression were assessed by RNA sequencing and Western Blot, respectively. RESULTS: Three or nine nights of sleep restriction had no effect on the muscle transcriptome independently of exercise. However, close to 3000 transcripts were differentially regulated (FDR < 0.05) 48 h post the completion of three resistance exercise sessions in both NS and SR conditions. Only 39% of downregulated and 18% of upregulated genes were common between both conditions, indicating a moderating effect of sleep restriction on the response to exercise. CONCLUSION: Sleep restriction and resistance exercise interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.

Sustained Sleep Restriction Reduces Resistance Exercise Quality and Quantity in Females.

INTRODUCTION: Female athletes sleep less and report more sleep problems than their male counterparts. Inadequate sleep reduces maximal strength in male athletes; however, little is known about the impact of sleep restriction (SR) on the quantity and quality of resistance exercise performed by female athletes. This study investigated the effect of nine nights of moderate SR on repeated resistance exercise performance, hormonal responses, and perceived fatigue in females. METHODS: Ten healthy, resistance-trained, eumenorrheic females age 18-35 yr underwent nine nights of SR (5-h time in bed) and normal sleep (NS; ≥7-h time in bed) in a randomized, crossover fashion with a minimum 6-wk washout. Participants completed four resistance exercise sessions per trial, with blood samples collected before and after exercise. Exercise performance was assessed using volume load, reactive strength index, and mean concentric velocity with rating of perceived exertion recorded after exercise. Participants completed awakening saliva sampling and the Multi-component Training Distress Scale daily. RESULTS: Volume load decreased trivially (<1%, P < 0.05) with SR. Mean concentric velocity per set was slower during SR for the lower-body (up to 15%, P < 0.05), but not the upper-body, compound lifts. Intraset velocity loss was up to 7% greater during SR for back squats ( P < 0.05). SR increased salivary cortisol area under the curve (by 42%), total training distress (by 84%), and session perceived exertion (by 11%). CONCLUSIONS: Sustained SR reduces markers of resistance exercise quality (bar velocity) more than quantity (volume load) and increases perceived effort at the same relative intensity in resistance-trained females. Markers of exercise quality and internal load may be more sensitive than volume load, to advise coaches to the decline in lifting performance for female athletes experiencing SR.

The effect of sex hormones on skeletal muscle adaptation in females.

Sex steroids, commonly referred to as sex hormones, are integral to the development and maintenance of the human reproductive system. In addition, male (androgens) and female (estrogens and progestogens) sex hormones promote the development of secondary sex characteristics by targeting a range of other tissues, including skeletal muscle. The role of androgens on skeletal muscle mass, function and metabolism has been well described in males, yet female specific studies are scarce in the literature. This narrative review summarises the available evidence around the mechanistic role of androgens, estrogens and progestogens in female skeletal muscle. An analysis of the literature indicates that sex steroids play important roles in the regulation of female skeletal muscle mass and function. The free fractions of testosterone and progesterone in serum were consistently associated with the regulation of muscle mass, while estrogens may be primarily involved in mediating the muscle contractile function in conjunction with other sex hormones. Muscle strength was however not directly associated with any hormone in isolation when at physiological concentrations. Importantly, recent evidence suggests that intramuscular sex hormone concentrations may be more strongly associated with muscle size and function than circulating forms, providing interesting opportunities for future research. By combining cross-sectional, interventional and mechanical studies, this review aims to provide a broad, multidisciplinary picture of the current knowledge of the effects of sex steroids on skeletal muscle in females, with a focus on the regulation of muscle size and function and an insight into their clinical implications. HighlightsFree testosterone, but not total testosterone, is associated with lean mass but not strength in pre- and post-menopausal females.Progesterone and estrogens may regulate muscle mass and strength, respectively, in females.Intra-muscular steroids may be more closely associated to muscle mass and strength, compared to systemic fractions.

Total testosterone is not associated with lean mass or handgrip strength in pre-menopausal females.

The aim of this study was to examine the relationship between endogenous testosterone concentrations and lean mass and handgrip strength in healthy, pre-menopausal females. Testosterone has been positively associated with lean mass and strength in young and older males. Whether this relationship exists in pre-menopausal females is unknown. Secondary data from the 2013-2014 National Health and Nutrition Examination Survey were used to test this relationship. Females were aged 18-40 (n = 716, age 30 ± 6 years, mean ± SD) and pre-menopausal. Multivariate linear regression models were used to examine associations between total testosterone, lean mass index (LMI) and handgrip strength. Mean ± SD testosterone concentration was 1.0 ± 0.6 nmol L-1 and mean free androgen index (FAI) was 0.02 ± 0.02. In pre-menopausal females, testosterone was not associated with LMI (ß = 0.05; 95%CI - 0.04, 0.15; p = 0.237) or handgrip strength (ß = 0.01; 95%CI - 0.11, 0.12; p = 0.926) in a statistically significant manner. Conversely, FAI was associated with LMI (ß = - 0.03; 95%CI - 0.05, - 0.02; p = 0.000) in a quadratic manner, meaning LMI increases with increasing FAI levels. Handgrip strength was not associated with FAI (ß = 0.06; 95%CI - 0.02, 0.15; p = 0.137). These findings indicate that FAI, but not total testosterone, is associated with LMI in pre-menopausal females. Neither FAI nor total testosterone are associated with handgrip strength in pre-menopausal females when testosterone concentrations are not altered pharmacologically.

Extracellular vesicular miRNA expression is not a proxy for skeletal muscle miRNA expression in males and females following acute, moderate intensity exercise.

Skeletal muscle and extracellular vesicle (EV) miRNA expression increases following acute endurance exercise. However, research to date has only been performed in males. The aim of this study was to describe the expression levels of a subset of miRNAs in EVs following acute exercise and compare it to skeletal muscle miRNA expression. Twelve males (age 22.9 ± 2.6 years, mean ± SD) and eight females (age 23.0 ± 3.4 years) cycled for 60 min at 70% VO2 peak. Muscle biopsies and blood samples were collected at rest, immediately after and 3 hr after exercise. Acute exercise did not significantly alter the expression of miR-1, miR-16, miR-23b and miR-133a/b in EVs in males and females combined. There were no correlations between EV and skeletal muscle miRNA expression in any of the measured species at any time point. Exploratory analysis revealed differential miRNA responses to exercise between males and females. In males, a weak negative correlation was observed between skeletal muscle and EV miR-16 expression immediately following exercise; however, the physiological relevance of this correlation is unknown. Additionally, when compared with values at rest, male skeletal muscle miR-16 expression significantly increased immediately following exercise, whereas miR-133a expression significantly decreased 3 hr post exercise. Our findings suggest that miRNAs isolated from EVs are not a proxy for skeletal muscle miRNA content. Our exploratory data is the first known evidence of sex-specific differences in the miRNA response to an acute bout of endurance exercise, particularly for miRNA species implicated in mitochondrial metabolism and angiogenesis.

Noncoding RNAs regulating cardiac muscle mass.

Noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) play roles in the development and homeostasis of nearly every tissue of the body, including the regulation of processes underlying heart growth. Cardiac hypertrophy can be classified as either physiological (beneficial heart growth) or pathological (detrimental heart growth), the latter of which results in impaired cardiac function and heart failure and is predictive of a higher incidence of death due to cardiovascular disease. Several miRNAs have a functional role in exercise-induced cardiac hypertrophy, while both miRNAs and lncRNAs are heavily involved in pathological heart growth and heart failure. The latter have the potential to act as an endogenous sponge RNA and interact with specific miRNAs to control cardiac hypertrophy, adding another level of complexity to our understanding of the regulation of cardiac muscle mass. In addition to tissue-specific effects, ncRNA-mediated tissue cross talk occurs via exosomes. In particular, miRNAs can be internalized in exosomes and secreted from various cardiac and vascular cell types to promote angiogenesis, as well as protection and repair of ischemic tissues. ncRNAs hold promising therapeutic potential to protect the heart against ischemic injury and aid in regeneration. Numerous preclinical studies have demonstrated the therapeutic potential of ncRNAs, specifically miRNAs, for the treatment of cardiovascular disease. Most of these studies employ antisense oligonucleotides to inhibit miRNAs of interest; however, off-target effects often limit their potential to be translated to the clinic. In this context, approaches using viral and nonviral delivery tools are promising means to provide targeted delivery in vivo.