Transcriptional and morphological responses following distinct muscle contraction protocols for Snell dwarf (Pit1dw/dw) mice.

The Snell dwarf mouse (Pit1dw/dw), an animal model of congenital combined pituitary hormone deficiency, displays skeletal muscle weakness. While enhanced responsivity to repeated exposures of muscle contractions have been documented for Snell dwarf mice, the response following single exposure to distinct contraction protocols remained uncharacterized. The purpose of this study was to investigate the muscle recovery of Snell dwarf and control littermate mice following a single exposure to two separate protocols-an intermittent slow velocity (30°/s) contraction protocol or a continuous rapid velocity (500°/s) contraction protocol. Following both protocols for control mice, torque values were 30% and 80% of pre-protocol values at 5 min and 3 days, respectively. At 10 days, performance returned to baseline for the 30°/s protocol and were depressed for the 500°/s protocol. For Snell dwarf mice following both protocols, torques were depressed to 5% of pre-protocol values at 5 min and returned to baseline by 3 days. Recovery following the 30°/s protocol for control mice and both protocols for Snell dwarf mice coincided with increased transcriptional output, upregulation of cytokine-mediated signaling genes, and a distribution shift to smaller muscle fibers with reduced area per nucleus. These features represent efficacious remodeling ubiquitous across distinct contraction paradigms in the context of the Pit1 mutation.

Comparison of the "Tall and Fall" Versus "Drop and Drive" Pitching Styles: Analysis of Major League Baseball Pitchers During a Single Season.

Background: Previous research has documented the proportion of "tall and fall" (TF) and "drop and drive" (DD) pitching styles among Major League Baseball (MLB) pitchers who underwent ulnar collateral ligament reconstruction (UCLR). The proportion of these 2 styles among all MLB pitchers remains unknown. Purpose: To determine the proportion of the TF and DD pitching styles in all rostered MLB pitchers during a single season as well as the proportion of TF and DD pitchers who sustained an upper extremity (UE) injury and those who underwent UCLR. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Pitcher demographic characteristics from the 2019 MLB season and pitching information were obtained via open-access sources. Two-dimensional video analysis was used to categorize the included pitchers into TF and DD groups. Statistical comparisons and contrasts were made using 2-tailed t tests, chi-square tests, and Pearson correlation analyses as appropriate. Results: Of the 660 MLB rostered pitchers in 2019 (age, 27.39 ± 3.51 years; body mass index, 26.34 ± 2.47 kg/m2; fastball velocity, 150.49 ± 3.99 kph [93.51 ± 2.48 mph]), 412 (62.4%) pitchers used the TF style and 248 (37.6%) pitchers used the DD style. Significantly more UE injuries were seen in the TF group compared with the DD group (112 vs 38 injuries, respectively; P < .001). Twelve pitchers underwent UCLR (TF, 10; DD, 2), representing a 1.8% UCLR rate among all pitchers. This was a second surgery for 2 pitchers, both of whom used the TF pitching style. Significantly more pitchers in the TF group than the DD group had undergone UCLR before 2019 (135 vs 56 pitchers, respectively; P = .005). Conclusion: The results of the present study demonstrated a higher prevalence of both UE injury and prior UCLR in TF pitchers. Further research is needed to explore the potential association between pitching style and UE injury.

Elevated muscle mass accompanied by transcriptional and nuclear alterations several months following cessation of resistance-type training in rats.

Rodent studies investigating long-term effects following termination of hypertrophy-inducing loading have predominantly involved exposures such as synergist ablation and weighted wheel running or ladder climbing. This research yielded a spectrum of results regarding the extent of detraining in terms of muscle mass and myonuclei number. The studies were also limited in their lack of sensitive performance measures and indirect relatedness to resistance training. Our research group developed and validated a relevant rat model of resistance-type training that induces increased muscle mass and performance. The aim of the present study was to determine to what extent these features persist 3 months following the termination of this training. While performance returned to baseline, muscle mass remained elevated by 17% and a shift in distribution to larger muscle fibers persisted. A 16% greater total RNA and heightened mRNA levels of ribosomal protein S6 kinases implicated preserved transcriptional output and ribosomal content. Remodeling of muscle fiber nuclei was consistent with these findings - increased nuclear number and a distribution shift to a more circular nuclear shape. These findings indicate that muscle mass detrains at a slower rate than performance and implicates multiple forms of myonuclear remodeling in muscle memory.

Retrospective Analysis of Ulnar Collateral Ligament Reconstructions in Major League Baseball Pitchers: A Comparison of the "Tall and Fall" Versus "Drop and Drive" Pitching Styles.

Background: Previous pilot research has investigated differences in elbow valgus torque between the "tall and fall" (TF) and "drop and drive" (DD) pitching styles. Whether one of these pitching styles is associated with a greater rate of ulnar collateral ligament reconstruction (UCLR) is currently unknown. Purpose: To determine the proportion of Major League Baseball (MLB) pitchers using the TF and DD pitching styles who underwent UCLR over a 10-year period. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The demographic characteristics of pitchers who underwent UCLR between 2007 and 2017 were obtained via the open-source database MLB Player Analysis Tommy John Surgery List. Other information, such as previous UCLR and pitching videos and graphics, was obtained from other open-source databases. A comprehensive, 2-dimensional, kinesiology-based multicomponent definition of each pitching style was formulated and used to categorize the included pitchers into the TF and DD groups. Statistical comparisons and contrasts were made using chi-square and Pearson correlation tests. Results: Included were 223 MLB pitchers (mean ± SD age, 27.5 ± 3.6 years; body mass index [BMI], 27.6 ± 2.2; throwing velocity, 92.9 ± 2.6 mph [149.5 ± 4.2 km/h]) who underwent UCLR between 2007 and 2017. Of these pitchers, 162 were categorized as TF pitchers (72.6%) and 61 as DD pitchers (27.4%). Pitching velocity for injured pitchers was significantly correlated to BMI (P < .001). We found no significant associations of pitching style with year of UCLR (P = .941), BMI (P = .549), age (P = .647), handedness (P = .501), or average pitch velocity (P = .921). Conclusion: The study findings demonstrated that a higher proportion of UCL-injured MLB pitchers (72.6%) used the TF pitching style. Further research is needed to explore the potential association between pitching style and UCL injury.

Improved impedance to maladaptation and enhanced VCAM-1 upregulation with resistance-type training in the long-lived Snell dwarf (Pit1dw/dw) mouse.

Snell dwarf mice with the Pit1dw/dw mutation are deficient in growth hormone, prolactin, and thyroid stimulating hormone and exhibit >40% lifespan extension. This longevity is accompanied by compromised muscular performance. However, research regarding young (3-month-old) Snell dwarf mice demonstrate exceptional responsivity to resistance-type training especially in terms of a shifted fiber type distribution and increased protein levels of vascular cell adhesion molecule-1 (VCAM-1), a possible mediator of such remodeling. In the present study, we investigated whether this responsiveness persists at 12 months of age. Unlike 12-month-old control mice, age-matched Snell dwarf mice remained resistant to training-induced maladaptive decreases in performance and muscle mass. This was accompanied by retainment of the remodeling capacity in muscles of Snell dwarf mice to increase VCAM-1 protein levels and a shift in myosin heavy chain (MHC) isoform distribution with training. Even decreasing training frequency for control mice, an alteration which protected muscles from maladaptation at 12 months of age, did not result in the overt remodeling observed for Snell dwarf mice. The results demonstrate a distinct remodeling response to resistance-type exercise operative in the context of the Pit1dw/dw mutation of long-lived Snell dwarf mice.

Age-dependent stress response DNA demethylation and gene upregulation accompany nuclear and skeletal muscle remodeling following acute resistance-type exercise in rats.

Efficacy of high-intensity resistance exercise becomes progressively compromised with aging. Previously, to investigate this, we developed a rodent model of high-intensity training consisting of stretch-shortening contractions (SSCs) and determined that following one month of training, young rats exhibit a robust stress response and 20% performance increase, whereas old rats display a muted stress response and 30% performance decrease. Whether these age-specific responses occur early in training and constitute primary factors in adaptation/maladaptation was not addressed. The aim of the present study was to characterize performance, remodeling, and stress response transcriptional profile 6-120 h following acute SSC exposure. For young rats, the stress response pathway was highly regulated (≥20 differentially expressed genes at each time point) and was accompanied by robust DNA demethylation, tissue remodeling, and isometric torque recovery. For old rats, a muted transcriptional profile (13 and 2 differentially expressed genes at 6 and 120 h, respectively) coincided with deficiencies in demethylation, muscle remodeling, and torque recovery. These findings occurred in the context of heightened chronic levels of stress response gene expression with aging. This demonstrates that age-related constitutive elevations in stress response gene expression was accompanied by diminished SSC-induced responsiveness in epigenomic regulation and tissue remodeling.

Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats.

Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported that skeletal muscle L1 expression is lower following acute and chronic exercise training in humans. Herein, we used a rodent model of voluntary wheel running to determine whether long-term exercise training affects markers of skeletal muscle L1 regulation. Selectively bred high-running female Wistar rats (n = 11 per group) were either given access to a running wheel (EX) or not (SED) at 5 wk of age, and these conditions were maintained until 27 wk of age. Thereafter, mixed gastrocnemius tissue was harvested and analyzed for L1 mRNA expression and DNA content along with other L1 regulation markers. We observed significantly (P < 0.05) lower L1 mRNA expression, higher L1 DNA methylation, and less L1 DNA in accessible chromatin regions in EX versus SED rats. We followed these experiments with 3-h in vitro drug treatments in L6 myotubes to mimic transient exercise-specific signaling events. The AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR; 4 mM) significantly decreased L1 mRNA expression in L6 myotubes. However, this effect was not facilitated through increased L1 DNA methylation. Collectively, these data suggest that long-term voluntary wheel running downregulates skeletal muscle L1 mRNA, and this may occur through chromatin modifications. Enhanced AMPK signaling with repetitive exercise bouts may also decrease L1 mRNA expression, although the mechanism of action remains unknown.

Reduced frequency of resistance-type exercise training promotes adaptation of the aged skeletal muscle microenvironment.

The purpose of this study was to characterize the growth and remodeling molecular signaling response in aged skeletal muscle following 1 mo of "resistance-type exercise" training. Male Fischer 344 × Brown Norway hybrid rats aged 3 (young) and 30 mo (old) underwent stretch-shortening contraction (SSC) loading 2 or 3 days/wk; muscles were removed 72 h posttraining. Young rats SSC loaded 3 (Y3x) or 2 days/wk (Y2x) adapted via increased work performance. Old rats SSC loaded 3 days/wk (O3x) maladapted via decreased negative work; however, old rats SSC loaded 2 days/wk (O2x) adapted through improved negative and positive work. Y3x, Y2x, and O2x, but not O3x, displayed hypertrophy via larger fiber area and myonuclear domains. Y3x, Y2x, and O2x differentially expressed 19, 30, and 8 phosphatidylinositol 3-kinase-Akt genes, respectively, whereas O3x only expressed 2. Bioinformatics analysis revealed that rats in the adapting groups presented growth and remodeling processes (i.e., increased protein synthesis), whereas O3x demonstrated inflammatory signaling. In conclusion, reducing SSC-loading frequency in aged rodents positively influences the molecular signaling microenvironment, promoting muscle adaptation. NEW & NOTEWORTHY Decreasing resistance-type exercise training frequency in old rodents led to adaptation through enhancements in performance, fiber areas, and myonuclear domains. Modifying frequency influenced the molecular environment through improvements in phosphatidylinositol 3-kinase-Akt pathway-specific expression and bioinformatics indicating increased protein synthesis. Reducing training frequency may be appropriate in older individuals who respond unfavorably to higher frequencies (i.e., maladaptation); overall, modifying the parameters of the exercise prescription can affect the cellular environment, ultimately leading to adaptive or maladaptive outcomes.

VCAM-1 upregulation accompanies muscle remodeling following resistance-type exercise in Snell dwarf (Pit1dw/dw ) mice.

Snell dwarf mice (Pit1dw/dw ) exhibit deficiencies in growth hormone, prolactin, and thyroid stimulating hormone. Besides being an experimental model of hypopituitarism, these mice are long-lived (>40% lifespan extension) and utilized as a model of slowed/delayed aging. Whether this longevity is accompanied by a compromised quality of life in terms of muscular performance has not yet been characterized. In this study, we investigated nontrained and trained muscles 1 month following a general validated resistance-type exercise protocol in 3-month-old Snell dwarf mice and control littermates. Nontrained Snell dwarf gastrocnemius muscles exhibited a 1.3-fold greater muscle mass to body weight ratio than control values although muscle quality, maximum isometric torque normalized to muscle mass, and fatigue recovery were compromised. For control mice, training increased isometric torque (17%) without altering muscle mass. For Snell dwarf mice, isometric torque was unaltered by training despite decreased muscle mass that rendered muscle mass to body weight ratio comparable to control values. Muscle quality and fatigue recovery improved twofold and threefold, respectively, for Snell dwarf mice. This accompanied a fourfold increase in levels of vascular cell adhesion molecule-1 (VCAM-1), a mediator of progenitor cell recruitment, and muscle remodeling in the form of increased number of central nuclei, additional muscle fibers per unit area, and altered fiber type distribution. These results reveal a trade-off between muscle quality and longevity in the context of anterior pituitary hormone deficiency and that resistance-type training can diminish this trade-off by improving muscle quality concomitant with VCAM-1 upregulation and muscle remodeling.

High-intensity stretch-shortening contraction training modifies responsivity of skeletal muscle in old male rats.

Utilization of high-intensity resistance training to counter age-related sarcopenia is currently debated because of the potential for maladaptation when training design is inappropriate. Training design is problematic because the influence of various loading variables (e.g. contraction mode, repetition number, and training frequency) is still not well characterized at old age. To address this in a precisely controlled manner, we developed a rodent model of high-intensity training consisting of maximally-activated stretch-shortening contractions (SSCs), contractions typical during resistance training. With this model, we determined that at old age, high-repetition SSC training (80 SSCs: 8 sets of 10 repetitions) performed frequently (i.e. 3 days per week) for 4.5 weeks induced strength deficits with no muscle mass gain while decreasing frequency to 2 days per week promoted increases in muscle mass and muscle quality (i.e. performance normalized to muscle mass). This finding confirmed the popular notion that decreasing training frequency has a robust effect with age. Meanwhile, the influence of other loading variables remains contentious. The aim of the present study was to assess muscle adaptation following modulation of contraction mode and repetition number during high-intensity SSC training. Muscles of young (3 month old) and old (30 month old) male rats were exposed to 4.5 weeks of low-repetition static training of 4 (i.e. 4 sets of one repetition) isometric (ISO) contractions 3 days per week or a more moderate-repetition dynamic training of 40 SSCs (i.e. 4 sets of 10 repetitions) 3 days per week. For young rats, performance and muscle mass increased regardless of training protocol. For old rats, no muscle mass adaptation was observed for 4 ISO training while 40 SSC training induced muscle mass gain without improvement in muscle quality, an outcome distinct from modulating training frequency. Muscle mass gain for old rats was accompanied by decreased protein levels of tumor necrosis factor alpha, a mediator of age-related chronic inflammatory signaling, to young levels. These findings suggest that while dynamic high-intensity training with a moderate number of repetitions has a limited capacity for altering muscle quality, such training is a viable strategy for countering age-related inflammatory signaling and modifying muscle mass.

Efficacy of Age-Specific High-Intensity Stretch-Shortening Contractions in Reversing Dynapenia, Sarcopenia, and Loss of Skeletal Muscle Quality.

During the aging process, skeletal muscle performance and physiology undergoes alterations leading to decrements in functional capacity, health-span, and independence. Background: The utility and implementation of age-specific exercise is a paramount research agenda focusing on ameliorating the loss of both skeletal muscle performance and physiology; yet, to date, no consensus exists as to the most appropriate mechanical loading protocol design or overall exercise prescription that best meets this need. Thus, the purpose of this review is to highlight the most optimal type of exercise presently available and provide the most current, evidence-based findings for its efficacy. The hypothesis that high-intensity, stretch-shortening contractions (SSCs)-a form of "resistance-type exercise" training-present as the preferred exercise mode for serving as an intervention-based modality to attenuate dynapenia, sarcopenia, and decreased muscle quality with aging, even restoring the overall youthful phenotype, will be demonstrated. Conclusions: Appreciating the fundamental evidence supporting the use of high-intensity SSCs in positively impacting aging skeletal muscle's responsivity and their use as a specific and sensitive countermeasure is crucial. Moreover, from an applied perspective, SSCs may improve skeletal muscle quality and rejuvenate health-span and, ultimately, lead to augmented functional capacity, independence, and quality of life concomitant with decreased morbidity.

Inflammaging and the Age-Specific Responsiveness to Stretch-Shortening Contractions.

With aging, muscle injury from rapid, continuous stretch-shortening contractions (SSC) is prolonged, and maladaptation to moderate-velocity, intermittent SSC is more common. We hypothesize that high baseline levels of inflammatory signaling and oxidative stress may underlie these outcomes, whereas careful modulation of high-intensity SSC training design resets basal conditions and permits muscle adaptation to SSC.

Agonist muscle adaptation accompanied by antagonist muscle atrophy in the hindlimb of mice following stretch-shortening contraction training.

BACKGROUND: The vast majority of dynamometer-based animal models for investigation of the response to chronic muscle contraction exposure has been limited to analysis of isometric, lengthening, or shortening contractions in isolation. An exception to this has been the utilization of a rat model to study stretch-shortening contractions (SSCs), a sequence of consecutive isometric, lengthening, and shortening contractions common during daily activity and resistance-type exercise. However, the availability of diverse genetic strains of rats is limited. Therefore, the purpose of the present study was to develop a dynamometer-based SSC training protocol to induce increased muscle mass and performance in plantarflexor muscles of mice. METHODS: Young (3 months old) C57BL/6 mice were subjected to 1 month of plantarflexion SSC training. Hindlimb muscles were analyzed for muscle mass, quantitative morphology, myogenesis/myopathy relevant gene expression, and fiber type distribution. RESULTS: The main aim of the research was achieved when training induced a 2-fold increase in plantarflexion peak torque output and a 19% increase in muscle mass for the agonist plantaris (PLT) muscle. In establishing this model, several outcomes emerged which raised the value of the model past that of being a mere recapitulation of the rat model. An increase in the number of muscle fibers per transverse muscle section accounted for the PLT muscle mass gain while the antagonist tibialis anterior (TA) muscle atrophied by 30% with preferential atrophy of type IIb and IIx fibers. These alterations were accompanied by distinct gene expression profiles. CONCLUSIONS: The findings confirm the development of a stretch-shortening contraction training model for the PLT muscle of mice and demonstrate that increased cross-sectional fiber number can occur following high-intensity SSC training. Furthermore, the TA muscle atrophy provides direct evidence for the concept of muscle imbalance in phasic non-weight bearing muscles, a concept largely characterized based on clinical observation of patients. The susceptibility to this imbalance is demonstrated to be selective for the type IIb and IIx muscle fiber types. Overall, the study highlights the importance of considering muscle fiber number modulation and the effect of training on surrounding muscles in exercise comprised of SSCs.

An Old Problem: Aging and Skeletal-Muscle-Strain Injury.

Clinical Scenario: 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. CLINICAL RELEVANCE: 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.

Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch-Shortening Contraction Training.

Exercise is the most accessible, efficacious, and multifactorial intervention to improve health and treat chronic disease. High-intensity resistance exercise, in particular, also maximizes skeletal muscle size and strength-outcomes crucial at advanced age. However, such training is capable of inducing muscle maladaptation when misapplied at old age. Therefore, characterization of parameters (e.g., mode and frequency) that foster adaptation is an active research area. To address this issue, we utilized a rodent model that allowed training at maximal intensity in terms of muscle activation and tested the hypothesis that muscles of old rats adapt to stretch-shortening contraction (SSC) training, provided the training frequency is sufficiently low. At termination of training, normalized muscle mass (i.e., muscle mass divided by tibia length) and muscle quality (isometric force divided by normalized muscle mass) were determined. For young rats, normalized muscle mass increased by ∼20% regardless of training frequency. No difference was observed for muscle quality values after 2 days versus 3 days per week training (0.65 ± 0.09 N/mg/mm vs. 0.59 ± 0.05 N/mg/mm, respectively). For old rats following 3 days per week training, normalized muscle mass was unaltered and muscle quality was 30% lower than young levels. Following 2 days per week training at old age, normalized muscle mass increased by 17% and muscle quality was restored to young levels. To investigate this enhanced response, oxidative stress was assessed by lipid peroxidation quantification. For young rats, lipid peroxidation levels were unaltered by training. With aging, baseline levels of lipid peroxidation increased by 1.5-fold. For old rats, only 2 days per week training decreased lipid peroxidation to levels indistinguishable from young values. These results imply that, appropriately scheduled high-intensity SSC training at old age is capable of restoring muscle to a younger phenotype in terms of lipid peroxidation levels and muscle quality.

Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats.

Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P < 0.05). For 3 month old rats, maximum isometric force and dynamic peak force increased by 22 ± 8% and 27 ± 10%, respectively (P < 0.05). For 6 month old rats, these forces were unaltered by exposure and positive work capacity diminished by 27 ± 2% (P = 0.006). By 30 months of age, age-related deficits in maximum isometric force, peak force, negative work, and positive work were apparent and SSC exposure was ineffective at counteracting such deficits. Recovery from fatigue was also tested and exposure-induced improvements in fatigue recovery were indicated for 6 month old rats and to a lesser extent for 3 month old rats whereas no such effect was observed for older rats. Alterations in fatigue recovery were accompanied by evidence of substantial type IIb to IIx fiber type shifting. These results highlight the exceptional adaptive capacity for strength at a young age, the inclination for adaptation in fatigue recovery at early adulthood, and diminished adaptation for muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life.

Desensitized morphological and cytokine response after stretch-shortening muscle contractions as a feature of aging in rats.

Recovery from contraction-induced injury is impaired with aging. At a young age, the secondary response several days following contraction-induced injury consists of edema, inflammatory cell infiltration, and segmental muscle fiber degeneration to aid in the clearance of damaged tissue and repair. This morphological response has not been wholly established at advanced age. Our aim was to characterize muscle fiber morphology 3 and 10 days following stretch-shortening contractions (SSCs) varying in repetition number (i.e. 0, 30, 80, and 150) for young and old rats. For muscles of young rats, muscle fiber degeneration was overt at 3 days exclusively after 80 or 150 SSCs and returned significantly closer to control values by 10 days. For muscles of old rats, no such responses were observed. Transcriptional microarray analysis at 3 days demonstrated that muscles of young rats differentially expressed up to 2144 genes while muscles of old rats differentially expressed 47 genes. Bioinformatic analysis indicated that cellular movement was a major biological process over-represented with genes that were significantly altered by SSCs especially for young rats. Protein levels in muscle for various cytokines and chemokines, key inflammatory factors for cell movement, increased 3- to 50-fold following high-repetition SSCs for young rats with no change for old rats. This age-related differential response was insightful given that for control (i.e. 0 SSCs) conditions, protein levels of circulatory cytokines/chemokines were increased with age. The results demonstrate ongoing systemic low-grade inflammatory signaling and subsequent desensitization of the cytokine/chemokine and morphological response to contraction-induced injury with aging - features which accompany age-related impairment in muscle recovery.

Mechanistic Hierarchical Gaussian Processes.

The statistics literature on functional data analysis focuses primarily on flexible black-box approaches, which are designed to allow individual curves to have essentially any shape while characterizing variability. Such methods typically cannot incorporate mechanistic information, which is commonly expressed in terms of differential equations. Motivated by studies of muscle activation, we propose a nonparametric Bayesian approach that takes into account mechanistic understanding of muscle physiology. A novel class of hierarchical Gaussian processes is defined that favors curves consistent with differential equations defined on motor, damper, spring systems. A Gibbs sampler is proposed to sample from the posterior distribution and applied to a study of rats exposed to non-injurious muscle activation protocols. Although motivated by muscle force data, a parallel approach can be used to include mechanistic information in broad functional data analysis applications.

Magnetic resonance imaging of graded skeletal muscle injury in live rats.

INTRODUCTION: Increasing number of stretch-shortening contractions (SSCs) results in increased muscle injury. METHODS: Fischer Hybrid rats were acutely exposed to an increasing number of SSCs in vivo using a custom-designed dynamometer. Magnetic resonance imaging (MRI) imaging was conducted 72 hours after exposure when rats were infused with Prohance and imaged using a 7T rodent MRI system (GE Epic 12.0). Images were acquired in the transverse plane with typically 60 total slices acquired covering the entire length of the hind legs. Rats were euthanized after MRI, the lower limbs removed, and tibialis anterior muscles were prepared for histology and quantified stereology. RESULTS: Stereological analyses showed myofiber degeneration, and cellular infiltrates significantly increased following 70 and 150 SSC exposure compared to controls. MRI images revealed that the percent affected area significantly increased with exposure in all SSC groups in a graded fashion. Signal intensity also significantly increased with increasing SSC repetitions. DISCUSSION: These results suggest that contrast-enhanced MRI has the sensitivity to differentiate specific degrees of skeletal muscle strain injury, and imaging data are specifically representative of cellular histopathology quantified via stereological analyses.

Volitional Weight-Lifting in Rats Promotes Adaptation via Performance and Muscle Morphology prior to Gains in Muscle Mass.

Investigation of volitional animal models of resistance training has been instrumental in our understanding of adaptive training. However, these studies have lacked reactive force measurements, a precise performance measure, and morphological analysis at a distinct phase of training - when initial strength gains precede muscle hypertrophy. Our aim was to expose rats to one month of training (70 or 700 g load) on a custom-designed weight-lifting apparatus for analysis of reactive forces and muscle morphology prior to muscle hypertrophy. Exclusively following 700 g load training, forces increased by 21% whereas muscle masses remained unaltered. For soleus (SOL) and tibialis anterior (TA) muscles, 700 g load training increased muscle fiber number per unit area by ∼20% and decreased muscle fiber area by ∼20%. Additionally, number of muscle fibers per section increased by 18% for SOL muscles. These results establish that distinct morphological alterations accompany early strength gains in a volitional animal model of load-dependent adaptive resistance training.