Resistance-only and concurrent exercise induce similar myofibrillar protein synthesis rates and associated molecular responses in moderately active men before and after training.

Aerobic and resistance exercise (RE) induce distinct molecular responses. One hypothesis is that these responses are antagonistic and unfavorable for the anabolic response to RE when concurrent exercise is performed. This thesis may also depend on the participants' training status and concurrent exercise order. We measured free-living myofibrillar protein synthesis (MyoPS) rates and associated molecular responses to resistance-only and concurrent exercise (with different exercise orders), before and after training. Moderately active men completed one of three exercise interventions (matched for age, baseline strength, body composition, and aerobic capacity): resistance-only exercise (RE, n = 8), RE plus high-intensity interval exercise (RE+HIIE, n = 8), or HIIE+RE (n = 9). Participants trained 3 days/week for 10 weeks; concurrent sessions were separated by 3 h. On the first day of Weeks 1 and 10, muscle was sampled immediately before and after, and 3 h after each exercise mode and analyzed for molecular markers of MyoPS and muscle glycogen. Additional muscle, sampled pre- and post-training, was used to determine MyoPS using orally administered deuterium oxide (D2 O). In both weeks, MyoPS rates were comparable between groups. Post-exercise changes in proteins reflective of protein synthesis were also similar between groups, though MuRF1 and MAFbx mRNA exhibited some exercise order-dependent responses. In Week 10, exercise-induced changes in MyoPS and some genes (PGC-1ɑ and MuRF1) were dampened from Week 1. Concurrent exercise (in either order) did not compromise the anabolic response to resistance-only exercise, before or after training. MyoPS rates and some molecular responses to exercise are diminished after training.

Small peptides: could they have a big role in metabolism and the response to exercise?

Exercise is a powerful non-pharmacological intervention for the treatment and prevention of numerous chronic diseases. Contracting skeletal muscles provoke widespread perturbations in numerous cells, tissues and organs, which stimulate multiple integrated adaptations that ultimately contribute to the many health benefits associated with regular exercise. Despite much research, the molecular mechanisms driving such changes are not completely resolved. Technological advancements beginning in the early 1960s have opened new avenues to explore the mechanisms responsible for the many beneficial adaptations to exercise. This has led to increased research into the role of small peptides (<100 amino acids) and mitochondrially derived peptides in metabolism and disease, including those coded within small open reading frames (sORFs; coding sequences that encode small peptides). Recently, it has been hypothesized that sORF-encoded mitochondrially derived peptides and other small peptides play significant roles as exercise-sensitive peptides in exercise-induced physiological adaptation. In this review, we highlight the discovery of mitochondrially derived peptides and newly discovered small peptides involved in metabolism, with a specific emphasis on their functions in exercise-induced adaptations and the prevention of metabolic diseases. In light of the few studies available, we also present data on how both single exercise sessions and exercise training affect expression of sORF-encoded mitochondrially derived peptides. Finally, we outline numerous research questions that await investigation regarding the roles of mitochondrially derived peptides in metabolism and prevention of various diseases, in addition to their roles in exercise-induced physiological adaptations, for future studies.

Structural maturation of myofilaments in engineered 3D cardiac microtissues characterized using small angle x-ray scattering.

Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, and designing therapies. Here we use a method not commonly applied to biological materials, small angle x-ray scattering, to characterize the structural development of hiPSC-CMs within three-dimensional engineered tissues during their preliminary stages of maturation. An x-ray scattering experimental method enables the reliable characterization of the cardiomyocyte myofilament spacing with maturation time. The myofilament lattice spacing monotonically decreases as the tissue matures from its initial post-seeding state over the span of 10 days. Visualization of the spacing at a grid of positions in the tissue provides an approach to characterizing the maturation and organization of cardiomyocyte myofilaments and has the potential to help elucidate mechanisms of pathophysiology, and disease progression, thereby stimulating new biological hypotheses in stem cell engineering.

Zeptonewton and attotesla per centimeter metrology with coupled oscillators.

We present the coupled oscillator: A new mechanism for signal amplification with widespread application in metrology. We introduce the mechanical theory of this framework and support it by way of simulations. We present a particular implementation of coupled oscillators: A microelectromechanical system (MEMS) that uses one large (∼100mm) N52 magnet coupled magnetically to a small (∼0.25mm), oscillating N52 magnet, providing a force resolution of 200zN measured over 1s in a noiseless environment. We show that the same system is able to resolve magnetic gradients of 130aT/cm at a single point (within 500µm). This technology, therefore, has the potential to revolutionize force and magnetic gradient sensing, including high-impact areas such cardiac and brain imaging.

Delineating the contribution of ageing and physical activity to changes in mitochondrial characteristics across the lifespan.

Ageing is associated with widespread physiological changes prominent within all tissues, including skeletal muscle and the brain, which lead to a decline in physical function. To tackle the growing health and economic burdens associated with an ageing population, the concept of healthy ageing has become a major research priority. Changes in skeletal muscle mitochondrial characteristics have been suggested to make an important contribution to the reductions in skeletal muscle function with age, and age-related changes in mitochondrial content, respiratory function, morphology, and mitochondrial DNA have previously been reported. However, not all studies report changes in mitochondrial characteristics with ageing, and there is increasing evidence to suggest that physical activity (or inactivity) throughout life is a confounding factor when interpreting age-associated changes. Given that physical activity is a potent stimulus for inducing beneficial adaptations to mitochondrial characteristics, delineating the influence of physical activity on the changes in skeletal muscle that occur with age is complicated. This review aims to summarise our current understanding and knowledge gaps regarding age-related changes to mitochondrial characteristics within skeletal muscle, as well as to provide some novel insights into brain mitochondria, and to propose avenues of future research and targeted interventions. Furthermore, where possible, we incorporate discussions of the modifying effects of physical activity, exercise, and training status, to purported age-related changes in mitochondrial characteristics.

A Five-Week Periodized Carbohydrate Diet Does Not Improve Maximal Lactate Steady-State Exercise Capacity and Substrate Oxidation in Well-Trained Cyclists compared to a High-Carbohydrate Diet.

There is a growing interest in studies involving carbohydrate (CHO) manipulation and subsequent adaptations to endurance training. This study aimed to analyze whether a periodized carbohydrate feeding strategy based on a daily training session has any advantages compared to a high-carbohydrate diet in well-trained cyclists. Seventeen trained cyclists (VO2peak = 70.8 ± 6.5 mL·kg-1·min-1) were divided into two groups, a periodized (PCHO) group and a high-carbohydrate (HCHO) group. Both groups performed the same training sessions for five weeks. In the PCHO group, 13 training sessions were performed with low carbohydrate availability. In the HCHO group, all sessions were completed following previous carbohydrate intake to ensure high pre-exercise glycogen levels. In both groups, there was an increase in the maximal lactate steady state (MLSS) (PCHO: 244.1 ± 29.9 W to 253.2 ± 28.4 W; p = 0.008; HCHO: 235.8 ± 21.4 W to 246.9 ± 16.7 W; p = 0.012) but not in the time to exhaustion at MLSS intensity. Both groups increased the percentage of muscle mass (PCHO: p = 0.021; HCHO: p = 0.042) and decreased the percent body fat (PCHO: p = 0.021; HCHO: p = 0.012). We found no differences in carbohydrate or lipid oxidation, heart rate, and post-exercise lactate concentration. Periodizing the CHO intake in well-trained cyclists during a 5-week intervention did not elicit superior results to an energy intake-matched high-carbohydrate diet in any of the measured outcomes.