Although primarily considered a disorder of the elderly, emerging evidence suggests the antecedents of osteoporosis are established during childhood and adolescence. A complex interplay of genetic, environmental, hormonal and behavioral factors determines skeletal development, and a greater effort is needed to identify the most critical factors that establish peak bone strength. Indeed, knowledge of modifiable factors that determine skeletal development may permit optimization of skeletal health during growth and could potentially offset reductions in bone strength with aging. The peripubertal years represent a unique period when the skeleton is particularly responsive to loading exercises, and there is now overwhelming evidence that exercise can optimize skeletal development. While this is not controversial, the most effective exercise prescription and how much investment in this prescription is needed to significantly impact bone health continues to be debated. Despite considerable progress, these issues are not easy to address, and important questions remain unresolved. This review focuses on the key determinants of skeletal development, whether exercise during childhood and adolescence should be advocated as a safe and effective strategy for optimizing peak bone strength, and whether investment in exercise early in life protects against the development of osteoporosis and fractures later in life.
Joshua N. Farr, Deepika R. Laddu and Scott B. Going
Brent A. Baker
Even though chronological aging is an inevitable phenomenological consequence occurring in every living organism, it is biological aging that may be the most significant factor challenging our quality of life. Development of functional limitations, resulting from improper maintenance and restoration of various organ systems, ultimately leads to reduced health and independence. Skeletal muscle is an organ system that, when challenged, is often injured in response to varying stimuli. Overt muscle-strain injury can be traumatic, clinically diagnosable, properly managed, and a remarkably common event, yet our contemporary understanding of how age and environmental stressors affect the initial and subsequent induction of injury and how the biological processes resulting from this event are modifiable and, eventually, lead to functional restoration and healing of skeletal muscle and adjacent tissues is presently unclear. Even though the secondary injury response to and recovery from "contraction-induced" skeletal-muscle injury are impaired with aging, there is no scientific consensus as to the exact mechanism responsible for this event. Given the multitude of investigative approaches, particular consideration given to the appropriateness of the muscle-injury model, or research paradigm, is critical so that outcomes may be physiologically relevant and translational. In this case, methods implementing stretch-shortening contractions, the most common form of muscle movements used by all mammals during physical movement, work, and activity, are highlighted.
Understanding the fundamental evidence regarding how aging influences the responsivity of skeletal muscle to strain injury is vital for informing how clinicians approach and implement preventive strategies, as well as therapeutic interventions. From a practical perspective, maintaining or improving the overall health and tissue quality of skeletal muscle as one ages will positively affect skeletal muscle’s safety threshold and responsivity, which may reduce incidence of injury, improve recovery time, and lessen overall fiscal burdens.
Christopher C. Webster, Kathryn M. van Boom, Nur Armino, Kate Larmuth, Timothy D. Noakes, James A. Smith and Tertius A. Kohn
in heart disease, obesity, and T2D ( Ludwig et al., 2018 ). A few days of consuming the LCHF diet can increase postprandial blood glucose concentrations in healthy individuals and reduce the capacity of skeletal muscle to oxidize a carbohydrate load, suggesting a typical state of poor glucose
Lothar Stein, Constanze Pacht, Sibylle Junge, Tobias S. Kaeding, Momme Kück, Norbert Maassen, Torge Wittke and Vladimir Shushakov
Defects in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) cause CF. Absence of the CFTR may result in skeletal muscle dysfunction. Here, we tested skeletal muscle function in male adolescent patients with CF.
Ten CF and 10 control participants (age: 16.8 ± 0.6 years) performed 7 repetitive sets of maximum voluntary contractions (MVCs) and underwent an isometric fatigue test of the knee extensors. Electromyography (EMG) activity was recorded from the m. vastus lateralis (VL) and m. vastus medialis (VM).
In CF, the MVC torque was lower and correlated with the predicted forced expiratory volume in one second (r = .73, p = .012, n = 10). The M-wave in the VL was shorter in CF than in controls (18.6 ± 0.5 vs. 20.3 ± 0.5 ms, p < .028). In the VM, both the M-wave (4.96 ± 0.61 vs. 7.97 ± 0.60 mV, p = .001) and the EMG (0.29 ± 0.04 vs. 0.47 ± 0.04 mV, p = .004) amplitudes were smaller in CF.
The differences in the VL and VM EMG signals between the groups indicate that the lower MVC torque in CF did not result from the direct impact of a CFTR defect on the sarcolemmal excitability; the differences more likely resulted from the less developed musculature in the patients with CF.
Ildus I. Ahmetov, Olga L. Vinogradova and Alun G. Williams
The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5–90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40–50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin–NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.
Stefan M. Pasiakos, Holly L. McClung, James P. McClung, Maria L. Urso, Matthew A. Pikosky, Gregory J. Cloutier, Roger A. Fielding and Andrew J. Young
This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 ± 1 yr, body mass 80 ± 2 kg, and VO2peak 45 ± 1 ml · kg−1 · min−1) immediately (0 hr) and 3 hr after a 60-min bout of cycle exercise (60% ± 5% VO2peak). Corresponding muscle biopsies were also obtained under resting conditions. The phosphorylation status of insulin/IGF-PI3K molecular-signaling proteins, ubiquitin-proteasome-related gene expression, FOXO transcription factors, and myogenic regulatory factors in muscle samples was analyzed using multiplex analysis, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). A condition–time interaction was observed for Akt phosphorylation (p < .05) with multiplexing. Regardless of endurance exercise, Akt phosphorylation decreased and ERK phosphorylation increased at 3 hr compared with 0 hr (p < .05). Levels of p70S6K phosphorylation were 110% greater (p < .05) at 3 hr than at 0 hr using Western blots. MuRF mRNA expression postexercise increased; levels were 4.7- and 5.7-fold greater (p < .05) at 0 hr and 3 hr, respectively, than at rest with qRT-PCR. Atrogin mRNA expression was up-regulated 3.2-fold 3 hr postexercise compared with rest. These findings demonstrate modest changes in the molecular responses to moderate endurance exercise in the absence of nutrition. This study provides the groundwork for future investigations designed to optimize the metabolic conditions necessary to positively influence the cellular mechanisms specific to skeletal-muscle protein turnover during recovery from endurance exercise.
Martin J. Gibala
The contribution of amino acid oxidation to total energy expenditure is negligible during short-term intense exercise and accounts for 3–6% of the total adenosine triphosphate supplied during prolonged exercise in humans. While not quantitatively important in terms of energy supply, the intermediary metabolism of several amino acids—notably glutamate, alanine, and the branched-chain amino acids—afreets other metabolites .including the intermediates within the tricarboxylic acid (TCA) cycle. Glutamate appears to be a key substrate for the rapid increase in muscle TCA cycle intermediates (TCAI) that occurs at the onset of moderate to intense exercise, due to a rightward shift of the reaction catalyzed by alanine aminotransferase (glutamate + pyruvate <-> alanine + 2-oxoglutarate). The pool of muscle TCAI declines during prolonged exercise, and this has been attributed to an increase in leucine oxidation that relies on one of the TCAI. However, this mechanism does not appear to be quantitatively important due of the relatively low maximal activity of branched-chain oxoacid dehydrogenase, the key enzyme involved. It has been suggested that an increase in TCAI is necessary to attain high rates of aerobic energy production and that a decline in TCAI may be a causative factor in local muscle fatigue. These topics remain controversial, but recent evidence suggests that changes in TCAI during exercise are unrelated to oxidative energy provision in skeletal muscle.
Gianluca Vernillo, Alfredo Brighenti, Eloisa Limonta, Pietro Trabucchi, Davide Malatesta, Grégoire P. Millet and Federico Schena
To quantify changes in skeletal-muscle oxygenation and pulmonary O2 uptake (V̇O2) after an extreme ultratrail running bout.
Before (PRE) and after (POST) the race (330-km, 24000 D±), profiles of vastus lateralis muscle oxygenation (ie, oxyhemoglobin [O2Hb], deoxyhemoglobin [HHb], and tissue oxygenation index [TOI]) and V̇O2 were determined in 14 athletes (EXP) and 12 control adults (CON) during two 4-min constant-load cycling bouts at power outputs of 1 (p1) and 1.5 (p1.5) W/kg performed in randomized order.
At POST, normalized [HHb] values increased (p1, +38.0%; p1.5, +27.9%; P < .05), while normalized [O2Hb] (p1, –20.4%; p1.5, –14.4%; P < .05) and TOI (p1, –17.0%; p1.5, –17.7%; P < .05) decreased in EXP. V̇O2 values were similar (P > 0.05). An “overshoot“ in normalized [HHb]:V̇O2 was observed, although the increase was significant only during p1.5 (+58.7%, P = .003). No difference in the aforementioned variables was noted in CON (P > .05).
The concentric and, particularly, the eccentric loads characterizing this extreme ultratrail-running bout may have led to variations in muscle structure and function, increasing the local muscle deoxygenation profile and the imbalance between O2 delivery to working muscles and muscle O2 consumption. This highlights the importance of incorporating graded training, particularly downhill bouts, to reduce the negative influence of concentric and severe eccentric loads to the microcirculatory function and to enhance the ability of runners to sustain such loading.
Sunhyo Jeong and Michung Yoon
Ovariectomy leads to weight gain primarily in the form of adipose tissue in rodents. The authors investigated whether swimming improves ovariectomy-induced obesity through activation of peroxisome proliferatoractivated receptor α (PPARα) in the skeletal muscle of female ovariectomized (OVX) mice, an animal model of postmenopausal women. Female mice were randomly divided into 3 groups (n = 8/group): a sedentary sham-operated group, a sedentary OVX group, and a swim-trained OVX group. After mice were subjected to swim training or kept sedentary for 6 wk, the authors studied the effects of swimming on not only bodyweight gain, white adipose tissue (WAT) mass, adipocyte size, and skeletal-muscle lipid accumulation but also the expression of skeletal-muscle PPARα target genes. Sedentary OVX mice had significantly higher body weight and WAT than sedentary sham mice. However, swim training reduced body-weight gain, WAT mass, and adipocyte size of OVX mice. Swim-trained OVX mice had significantly lower levels of serum triglycerides and total cholesterol than sedentary OVX mice. Lipid accumulation in skeletal muscle was also markedly decreased by swimming. Concomitantly, swim training significantly increased mRNA levels of skeletal-muscle PPARα and its target enzymes, as well as uncoupling protein 3 (UCP3) responsible for fattyacid oxidation. These results suggest that swimming can effectively prevent weight gain, adiposity, adipocyte hypertrophy, and lipid disorders caused by ovariectomy, in part through the activation of PPARα and UCP3, in the skeletal muscle of female mice and may contribute to the alleviation of metabolic syndrome, including obesity, hyperlipidemia, and Type 2 diabetes in postmenopausal women.
Tamara A. Scerpella, Jodi N. Dowthwaite, Nicole M. Gero, Jill A. Kanaley and Robert J. Ploutz-Snyder
Mechanical loading during childhood and adolescence may yield skeletal benefits that persist beyond activity cessation and menarche. At 1 year pre- and 2 years post-menarche, nondominant forearm areal bone mineral density (aBMD), bone mineral content (BMC) and projected area (area) were compared in gymnasts (n = 9), ex-gymnasts (n = 8) and nongymnasts (n = 13). At both observations, gymnasts and ex-gymnasts had higher forearm aBMD, BMC and area than nongymnasts. gymnasts had higher postmenarcheal means than ex-gymnasts for all three parameters. Childhood mechanical loading yields skeletal advantages that persist at least 24 months after loading cessation and menarche. Continued postmenarcheal loading yields additional benefit.