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.

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.

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.

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.

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.

Skeletal muscle injury versus adaptation with aging: novel insights on perplexing paradigms.

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 glutathione depletion and age on skeletal muscle performance and morphology following chronic stretch-shortening contraction exposure.

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.

Effects of age and glutathione levels on oxidative stress in rats after chronic exposure to stretch-shortening contractions.

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.

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.

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.

Aging-dependent regulation of antioxidant enzymes and redox status in chronically loaded rat dorsiflexor muscles.

This study compares changes in the pro-oxidant production and buffering capacity in young and aged skeletal muscle after exposure to chronic repetitive loading (RL). The dorsiflexors from one limb of young and aged rats were loaded 3 times/week for 4.5 weeks using 80 maximal stretch-shortening contractions per session. RL increased H2O2 in tibialis anterior muscles of young and aged rats and decreased the ratio of reduced/oxidized glutathione and lipid peroxidation in aged but not young adult animals. Glutathione peroxidase (GPx) activity decreased whereas catalase activity increased with RL in muscles from young and aged rats. RL increased CuZn superoxide disumutase (SOD) and Mn SOD protein concentration and CuZn SOD activity in muscles from young but not aged animals. There were no changes in protein content for GPx-1 and catalase or messenger RNA for any of the enzymes studied. These data show that aging reduces the adaptive capacity of muscles to buffer increased pro-oxidants imposed by chronic RL.

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.

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.

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.

Impact of repetition number on muscle performance and histological response.

UNLABELLED: Skeletal muscle injury is major concern in sport- and occupation-related fields. PURPOSE: We investigated the effects of increasing stretch-shortening contraction (SSC) repetition number in vivo and the resulting changes in functional performance and quantitative morphometry in rat skeletal muscle. METHODS: Functional testing was performed on the ankle dorsiflexor muscles of Sprague-Dawley rats, which were randomly exposed to 30 SSC, 70 SSC, 150 SSC, or 15 isometric contractions of equal duration. Changes in functional performance and muscle morphometry were assessed at 48 h after exposure. Stereology was used to quantify the volume density of degenerative myofibers and normal myofibers in the tibialis anterior muscle from each group, as well as measures of inflammation and swelling and changes in the interstitial space. RESULTS: At 48 h there was a significant decline in isometric force for the 70- and 150-SSC groups (P < 0.05 and P < 0.05, respectively). Stereological measures indicated significant decreases in the percentage of volume density of normal myofibers in the 70- and 150-SSC groups (P < 0.05). Measures for percentage of volume density of degenerative myofibers and inflammation were increased (P < 0.0001 and P < 0.05, respectively) in the 70- and 150-SSC groups. Moreover, a significant increase in the percentage of volume density of degenerative myofibers in the 150-SSC group compared with the 70-SSC group was observed (P < 0.05). CONCLUSION: These data strongly suggest that exposure to increasing SSC repetitions results in increased functional decrements and morphometric indices of myofiber degeneration and inflammation, and that there is an apparent threshold (repetition number) at which this occurs.

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.

Quantitative histology and MGF gene expression in rats following SSC exercise in vivo.

PURPOSE: We investigated the effects of muscle length during stretch-shortening cycles (SSC) in vivo on changes in MGF gene expression and quantitative morphometry in rat skeletal muscle. METHODS: Dorsiflexor muscles of male Sprague-Dawley rats were exposed to seven sets of 10 SSC at 500 degrees .s(-1). Animals were randomly assigned to a long muscle length injury group (L-inj), short muscle length injury group (S-inj), or isometric group (Iso), with recoveries examined at 6 or 48 h post-injury for each group. Following exposure, animals were euthanized, and the tissue was prepared for either histology (quantitative morphometry) or RNA isolation, followed by quantitative real-time reverse transcriptase polymerase chain reaction. mRNA levels were measured for mechano-growth factor (MGF), while 18S ribosomal RNA served as the internal reference sample. RESULTS: Stereological measures indicative of edema and myofiber degeneration were significantly increased in the L-inj SSC group at 48 h when compared with the S-inj or Iso group. MGF mRNA was increased transiently at 6 h in the isometric group. In contrast, MGF mRNA was increased at 48 h in the S-inj, but was not increased at either time point in the L-inj group. CONCLUSION: These data strongly indicate that exposure to SSC at longer muscle lengths result in greater morphometric indices of inflammation and degeneration than SSC conducted at a shorter muscle lengths or isometric contractions, at the same time that the adaptation to SSC was prolonged and, apparently, not resolved in the L-inj group that was manifested by the lack of up-regulation in MGF mRNA.