Last data update: Jun 24, 2024. (Total: 47078 publications since 2009)
Records 1-26 (of 26 Records) |
Query Trace: Baker BA [original query] |
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NIOSH research efforts to prevent work-related musculoskeletal disorders
Barim MS , Brogan U , Meyers A , Victoroff T , Baker BA , Zheng L , Nasarwanji M , Ramsey J . Proc Hum Factors Ergon Soc 2023 67 836-839 NIOSH researchers are pioneering the study of musculoskeletal health as professional ergonomists. We examine physical and social components of work environments to mitigate musculoskeletal injury risks. Part of our mission is to reduce the burden of work-related musculoskeletal disorders (MSDs) through a focused program of research and prevention that protects workers from MSDs, helps management mitigate related risks and liabilities, and helps practitioners improve the efficacy of workplace interventions. The purpose of this discussion panel is to disseminate research findings and recommendations (1) to practitioners to interpret and apply the results of research to real-world problems, and (2) to inspire researchers to continue their efforts to protect the millions of workers at risk. © 2023 Human Factors and Ergonomics Society. |
Comparison of the "tall and fall" versus "drop and drive" pitching styles: Analysis of Major League Baseball pitchers during a single season
Beaudry MF , Beaudry AG , Bradley JP , Haynes DE , Holland G , Edwards A , Baker BA , Jacobson BR , Chetlin RD . Orthop J Sports Med 2023 11 (5) 23259671231173691 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/m(2); 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. |
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
Beaudry MF , Beaudry AG , Bradley JP , Davis S , Baker BA , Holland G , Jacobson BR , Chetlin RD . Orthop J Sports Med 2022 10 (10) 23259671221128041 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. |
Elevated muscle mass accompanied by transcriptional and nuclear alterations several months following cessation of resistance-type training in rats
Rader EP , Baker BA . Physiol Rep 2022 10 (20) e15476 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. |
Improved impedance to maladaptation and enhanced VCAM-1 upregulation with resistance-type training in the long-lived Snell dwarf (Pit1) mouse.
Rader EP , Naimo MA , Ensey J , Baker BA . Aging (Albany NY) 2022 14 1157-1185 ![]() Snell dwarf mice with the Pit1(dw/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 Pit1(dw/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.
Rader EP , Baker BA . Facets (Ott) 2020 5 (1) 455-473 ![]() 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.
Romero MA , Mumford PW , Roberson PA , Osburn SC , Parry HA , Kavazis AN , Gladden LB , Schwartz TS , Baker BA , Toedebusch RG , Childs TE , Booth FW , Roberts MD . Am J Physiol Cell Physiol 2019 317 (6) C1313-C1323 ![]() 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 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 if 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 weeks of age, and these conditions were maintained until 27 weeks 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 AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR; 4mM) significantly decreased L1 mRNA expression in L6 myotubes. However, this effect was not facilitated through increased L1 DNA methylation. Collectively, these data suggest 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, albeit the mechanism of action remains unknown. |
Efficacy of age-specific high-intensity stretch-shortening contractions in reversing dynapenia, sarcopenia, and loss of skeletal muscle quality
Baker BA . J Funct Morphol Kinesiol 2018 3 (2) 36 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. © 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
Reduced frequency of resistance-type exercise training promotes adaptation of the aged skeletal muscle microenvironment
Naimo MA , Rader EP , Ensey J , Kashon ML , Baker BA . J Appl Physiol (1985) 2019 126 (4) 1074-1087 The purpose of this study was to characterize the growth and remodeling molecular signaling response in aged skeletal muscle following one month of "resistance-type exercise" training. Male Fisher344x Brown Norway hybrid rats aged 3 (young) and 30 months (old) underwent stretch-shortening contraction (SSC) loading two or three days per week; muscles were removed 72 hours post-training. Young rats SSC-loaded three (Y3x) or two days per week (Y2x) adapted via increased work performance. Old rats SSC-loaded three days per week (O3x) maladapted via decreased negative work; however, old rats SSC-loaded two days per week (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 PI3K-AKT genes, respectively, whereas O3x only expressed two. 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. |
VCAM-1 upregulation accompanies muscle remodeling following resistance-type exercise in Snell dwarf (Pit1(dw/dw) ) mice
Rader EP , Naimo MA , Ensey J , Baker BA . Aging Cell 2018 17 (5) e12816 Snell dwarf mice (Pit1(dw/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
Rader EP , Naimo MA , Ensey J , Baker BA . Exp Gerontol 2018 104 118-126 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. 3days per week) for 4.5weeks induced strength deficits with no muscle mass gain while decreasing frequency to 2days 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 (3month old) and old (30month old) male rats were exposed to 4.5weeks of low-repetition static training of 4 (i.e. 4 sets of one repetition) isometric (ISO) contractions 3days per week or a more moderate-repetition dynamic training of 40 SSCs (i.e. 4 sets of 10 repetitions) 3days 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. |
Inflammaging and the age-specific responsiveness to stretch-shortening contractions
Rader EP , Baker BA . Exerc Sport Sci Rev 2017 45 (4) 195-200 With aging, muscle injury from rapid, continuous stretch-shortening contractions (SSCs) is prolonged and maladaptation to moderate-velocity, intermittent SSCs is more common. We investigate the hypothesis that high baseline levels of inflammatory signaling and oxidative stress may underlie these outcomes, while careful modulation of high-intensity SSC training design resets basal conditions and permits muscle adaptation to SSCs. |
Agonist muscle adaptation accompanied by antagonist muscle atrophy in the hindlimb of mice following stretch-shortening contraction training
Rader EP , Naimo MA , Ensey J , Baker BA . BMC Musculoskelet Disord 2017 18 (1) 60 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
Baker BA . J Sport Rehabil 2017 26 (2) 1-24 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 impact 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, and recovery, from "contraction-induced" skeletal muscle injury is impaired with aging, there is no scientific consensus as to the exact mechanism(s) 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 (SSCs), the most common form of muscular movements utilized 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 preventative 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 impact skeletal muscle's safety threshold, and responsivity, which may reduce induction of injury, improve recovery-time, and lessen overall fiscal burdens. |
Enhancement of skeletal muscle in aged rats following high-intensity stretch-shortening contraction training
Rader EP , Naimo MA , Layner KN , Triscuit AM , Chetlin RD , Ensey J , Baker BA . Rejuvenation Res 2016 20 (2) 93-102 Exercise is the most accessible, efficacious, and multifactoral 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) which 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 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 also observed for muscle quality values after 2 days vs 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 appropriately scheduled high-intensity stretch-shortening contraction training at old age is capable of restoring muscle to a younger phenotype in terms of lipid peroxidation levels and muscle quality. |
Changes in the expression of calcitonin gene-related peptide after exposure to injurious stretch-shortening contractions.
Johnson C , Miller GR , Baker BA , Hollander M , Kashon ML , Waugh S , Krajnak K . Exp Gerontol 2016 79 1-7 ![]() One of the factors that can result in musculoskeletal injuries, and time off work, is exposure to repetitive motion. The goal of this study was to determine if skeletal muscle injury induced by exposure to injurious stretch-shortening cycles (iSSCs), resulted in hyperalgesia in the hind limb and changes in calcitonin-gene related peptide (CGRP) immunolabeling in the dorsal root ganglia (DRG) in young and old male rats. METHODS: Young (3months) and old (30months) male Fisher 344xBN F1 rats were anesthetized with isoflurane and the left hind limbs were exposed to 15 sets of 10 SSCs. Control animals were exposed to a single bout of SSCs of equal intensity. Sensitivity to mechanical stimulation was assessed using von Frey filaments prior to beginning the experiment, and on days 2 and 9 following exposure to iSSCs. Rats were euthanized one, 3 or 10days after the exposure. The ipsilateral DRG were dissected from the L4-5 region of the spine, along with the left tibialis anterior (LTA) muscle. RESULTS: Rats exposed to iSSCs were more sensitive to mechanical stimulation than control rats 2days after the exposure, and showed a reduction in peak force 3days after exposure. Changes in sensitivity to pressure were not associated with increases in CGRP labeling in the DRG at 3days. However, 9days after exposure to iSSCs, old rats still displayed an increased sensitivity to mechanical stimulation, and this hyperalgesia was associated with an increase in CGRP immunolabeling in the DRG. Young rats exposed to iSSC did not display a change in CGRP immunolabeling and sensitivity to mechanical stimulation returned to control levels at 10days. CONCLUSIONS: These findings suggest that hyperalgesia seen shortly after exposure to iSSC is not influenced by CGRP levels. However, in cases where recovery from injury may be slower, as it is in older rats, CGRP may contribute to the maintenance of hyperalgesia. |
Age-dependent muscle adaptation after chronic stretch-shortening contractions in rats
Rader EP , Layner K , Triscuit AM , Chetlin RD , Ensey J , Baker BA . Aging Dis 2016 7 (1) 1-13 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
Rader EP , Layner KN , Triscuit AM , Kashon ML , Gu JK , Ensey J , Baker BA . Exp Gerontol 2015 72 138-49 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 10days 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 3days exclusively after 80 or 150 SSCs and returned significantly closer to control values by 10days. For muscles of old rats, no such responses were observed. Transcriptional microarray analysis at 3days 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. |
Magnetic resonance imaging of graded skeletal muscle injury in live rats
Cutlip RG , Hollander MS , Johnson GA , Johnson BW , Friend SA , Baker BA . Environ Health Insights 2014 8 31-9 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
Rader EP , Miller GR , Chetlin RD , Wirth O , Baker BA . Environ Health Insights 2014 8 1-9 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 approximately 20% and decreased muscle fiber area by approximately 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. |
Mechanistic hierarchical Gaussian processes
Wheeler MW , Dunson DB , Pandalai SP , Baker BA , Herring AH . J Am Stat Assoc 2014 109 (507) 894-904 ![]() 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. |
Vitamin E and C supplementation reduces oxidative stress, improves antioxidant enzymes and positive muscle work in chronically loaded muscles of aged rats
Ryan MJ , Dudash HJ , Docherty M , Geronilla KB , Baker BA , Haff GG , Cutlip RG , Alway SE . Exp Gerontol 2010 45 (11) 882-95 Aging is associated with increased oxidative stress. Muscle levels of oxidative stress are further elevated with exercise. The purpose of this study was to determine if dietary antioxidant supplementation would improve muscle function and cellular markers of oxidative stress in response to chronic repetitive loading in aging. The dorsiflexors of the left limb of aged and young adult Fischer 344 BrownxNorway rats were loaded 3 times weekly for 4.5 weeks using 80 maximal stretch-shortening contractions per session. The contra-lateral limb served as the intra-animal control. The rats were randomly assigned to a diet supplemented with Vitamin E and Vitamin C or normal non-supplemented rat chow. Biomarkers of oxidative stress were measured in the tibialis anterior muscle. Repetitive loading exercise increased maximal isometric force, negative work and positive work in the dorsiflexors of young adult rats. Only positive work increased in the aged animals that were supplemented with Vitamin E and C. Markers of oxidative stress (H(2)O(2), total GSH, GSH/GSSG ratio, malondialdehyde and 8-OHdG) increased in the tibialis anterior muscles from aged and young adult animals with repetitive loading, but Vitamin E and C supplements attenuated this increase. MnSOD activity increased with supplementation in the young adult animals. CuZnSOD and catalase activity increased with supplementation in young adult and aged animals and GPx activity increased with exercise in the non-supplemented young adult and aged animals. The increased levels of endogenous antioxidant enzymes after Vitamin E and C supplementation appear to be regulated by post-transcriptional modifications that are affected differently by age, exercise, and supplementation. These data suggest that antioxidant supplementation improves indices of oxidative stress associated with repetitive loading exercise and aging and improves the positive work output of muscles in aged rodents. |
Skeletal muscle injury versus adaptation with aging: novel insights on perplexing paradigms
Baker BA , Cutlip RG . Exerc Sport Sci Rev 2010 38 (1) 10-16 A growing body of data supports a view that skeletal muscle's response after mechanical loading does not always result in the classically reported "injury response." Furthermore, current evidence supports a model of muscle adaptation and/or maladaptation, distinct from overt injury, in which myofiber degeneration and inflammation do not contribute as significantly as once reported even in aged populations. |
Effects of age and glutathione levels on oxidative stress in rats after chronic exposure to stretch-shortening contractions
Hollander MS , Baker BA , Ensey J , Kashon ML , Cutlip RG . Eur J Appl Physiol 2009 108 (3) 589-97 We investigated effects of age and glutathione synthesis inhibition on the oxidative stress status of tibialis anterior muscles from young and old Fisher 344 x Brown Norway male rats after chronic administration of stretch-shortening contractions. Oral supplementation of L: -buthionine-(S,R)-sulfoximine (BSO) inhibited glutathione synthesis. Dorsiflexor muscles in the hindlimb were exposed to 80 maximal stretch-shortening contractions (SSCs) three times per week for 4.5 weeks. We measured malondialdehyde, hydrogen peroxide (H(2)O(2)), and free isoprostanes to determine oxidative stress. Glutathione peroxidase activity was measured as an indicator of H(2)O(2) scavenging. Glutathione measurements confirmed the effectiveness of BSO treatment. In young rats, the SSC exposure protocol prevented oxidative stress and enhanced H(2)O(2) scavenging. In old rats, malondialdehyde was increased in the exposed muscle and a BSO-induced increase in H(2)O(2) was not alleviated with SSC exposure as seen in young rats. In addition, glutathione peroxidase activity and total glutathione were increased in old rats relative to their young counterparts. All comparisons were significant at the 0.05 level. Overall, BSO administration was effective in decreasing total glutathione levels and increasing H(2)O(2) levels in old and young rats exposed to SSCs. In addition, effects of chronic exposure to high-force resistive loading SSCs in active muscle from old animals are: (1) antioxidant capacity is enhanced similar to what is seen with endurance training and (2) oxidative stress is increased, probably as a consequence of the enhanced vulnerability due to aging. |
Effects of glutathione depletion and age on skeletal muscle performance and morphology following chronic stretch-shortening contraction exposure
Baker BA , Hollander MS , Kashon ML , Cutlip RG . Eur J Appl Physiol 2009 108 (3) 619-30 The involvement of glutathione in the response of skeletal muscle following repetitive, high-intensity mechanical loading is not known. We examined the influence of a glutathione antagonist [L: -Buthionine Sulfoximine (BSO)] had on the adaptability of skeletal muscle during chronic mechanical loading via stretch-shortening contractions (SSCs) in young and old rats. Left dorsiflexor muscles of young (12 weeks, N = 16) and old (30 months, N = 16), vehicle- and BSO-treated rats were exposed three times per week for 4.5-weeks to a protocol of 80 maximal SSCs per exposure in vivo. Skeletal muscle response to the SSC exposure was characterized by muscle performance, as well as muscle wet-weight and quantitative morphological analyses following the exposure period. Results reveal that generally, muscle performance increased in the young rats only following chronic SSC exposure. BSO treatment had no effect on muscle performance or morphology following the chronic SSC exposure in old rats. Muscle wet-weight was increased following exposure compared with the contra-lateral control limb, irrespective of age (p < 0.05). Muscle cross-sectional area increased approximately 20% with SSC loading in the young, vehicle rats, while increasing approximately 10% with SSC loading in old, vehicle rats compared with control rat muscle. No degenerative myofibers were noted in either age group, but edema were increased as a result of aging (p < 0.05). We conclude that our results indicate that glutathione depletion does not adversely affect muscle performance or morphology in old rats. Nevertheless, we continue to show that aging negatively influences performance and morphology following chronic SSC exposure. |
Injury and adaptive mechanisms in skeletal muscle
Cutlip RG , Baker BA , Hollander M , Ensey J . J Electromyogr Kinesiol 2009 19 (3) 358-72 Work-related musculoskeletal disorders (MSD) are a major concern in the United States. Overexertion and repetitive motion injuries dominate reporting of lost-time MSD incidents. Over the past three decades, there has been much study on contraction-induced skeletal muscle injury. The effect of the biomechanical loading signature that includes velocity, range of motion, the number of repetitions, force, work-rest cycle, and exposure duration has been studied. More recently, the effect of aging on muscle injury susceptibility and regeneration has been studied. This review will focus on contraction-induced skeletal muscle injury, the effects of repetitions, range of motion, work-rest cycles, and aging on injury susceptibility and regenerative and adaptive pathways. The different physiological phenomena responsive to overt muscle injury versus adaptation will be distinguished. The inherent capability of skeletal muscle to adapt to mechanical loading, given the appropriate exposure signature will also be discussed. Finally, we will submit that repeated high-intensity mechanical loading is a desirable means to attenuate the effects of sarcopenia, and may be the most effective and appealing mode of physical activity to counteract the effects often observed with musculo-skeletal dysfunction in the workplace. |
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