Six weeks of localized passive heat therapy elicits some exercise-like improvements in resistance artery function.

The purpose of this study was to examine the effects of 6 weeks of localized, muscle-focused (quadriceps femoris) passive heat therapy (PHT) on resistance artery function, exercise haemodynamics and exercise performance relative to knee extension (KE) exercise training (EX). We randomized 34 healthy adults (ages 18-36; n = 17 female, 17 male) to receive either PHT or sham heating sessions (120 min, 3 days/week), or EX (40 min, 3 days/week) over 6 weeks. Blood flow was assessed with Doppler ultrasound of the femoral artery during both passive leg movement (PLM) and a KE graded exercise test. Muscle biopsies were taken from the vastus lateralis at baseline and after 6 weeks. Peak blood flow during PLM increased to the same extent in both the EX (∼10.5% increase, P = 0.009) and PHT groups (∼8.5% increase, P = 0.044). Peak flow during knee extension exercise increased in EX (∼19%, P = 0.005), but did not change in PHT (P = 0.523) and decreased in SHAM (∼7%, P = 0.020). Peak vascular conductance during KE increased by ∼25% in EX (P = 0.030) and PHT (P = 0.012). KE peak power increased in EX by ∼27% (P = 0.001) but did not significantly change in PHT and SHAM groups. Expression of endothelial nitric oxide synthase increased significantly in both EX (P = 0.028) and PHT (P = 0.0095), but only EX resulted in increased angiogenesis. In conclusion, 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not yield significant improvements in performance. KEY POINTS: Many for whom exercise would be most beneficial are either unable to exercise or have a very low exercise tolerance. In these cases, an alternative treatment to combat declines in resistance artery function is needed. We tested the hypothesis that passive heat therapy (PHT) would increase resistance artery function, improve exercise haemodynamics and enhance exercise performance compared to a sham treatment, but less than aerobic exercise training. This report shows that 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not improve exercise performance. Additionally, muscle biopsy analyses revealed that endothelial nitric oxide synthase expression increased in both PHT and exercise training groups, but only exercise resulted in increased angiogenesis. Our data demonstrate the efficacy of applying passive heat as an alternative treatment to improve resistance artery function for those unable to receive the benefits of regular exercise.

Menstrual cycle phase differences in myofiber damage and macrophage infiltration following electrical stimulation-induced muscle injury.

The purpose of this study was to examine the effects of menstrual cycle phase on myofiber injury, regenerative events and inflammation after electrical-stimulation (ES) induced myofiber damage. 28 premenopausal women (21.3 ± 2 yrs) were randomized into an early follicular (EF; N=14) or late follicular (LF; N = 14) group. After menstrual cycle tracking and phase confirmation, subjects underwent 200 electrically stimulated eccentric muscle contractions one week after providing a muscle biopsy. 7 days post-ES, subjects provided a final biopsy. Primary outcomes included: serum estradiol, indirect markers of muscle damage, direct indicators of myofiber necrosis and regeneration, satellite cell number, and macrophage infiltration. Women in the LF group had higher serum estradiol (122.1 ± 23.4 vs. 81.7 ± 30.8 pg/ml; P<0.001)compared to the EF group on the day of ES. Whereas the EF group recovered baseline maximal isometric strength by 4 days post-ES, the LF group did not. Only women in the LF group showed significant and consistent evidence of myofiber necrosis and regeneration pre- to post-ES. Despite showing more evidence of myofiber damage, women in the LF group also experienced reduced total and CD206+ macrophage infiltration relative to the EF group. Satellite cell quantity increased significantly post-ES in both groups, with no differences between groups. Collectively, the data suggest that the high estrogen LF phase may be associated with increased susceptibility to myofiber injury while also limiting the subsequent intramuscular inflammatory response.

Physiological assessment of a 16 day, 4385 km ultra-endurance mountain bike race: A case study.

The Tour Divide (TD) is a 4385 km ultra-endurance bicycle race that follows the continental divide from Canada to Mexico. In this case study, we performed a comprehensive molecular and physiological profile before and after the completion of the TD. Assessments were performed 35 days before the start (Pre-TD) and ∼36 h after the finish (Post-TD). Total energy expenditure was assessed during the first 9 days by doubly labelled water (2 H2 18 O), abdominal and leg tissue volumes via MRI, and graded exercise tests to quantify fitness and substrate preference. Vastus lateralis muscle biopsies were taken to measure mitochondrial function via respirometry, and vascular function was assessed using Doppler ultrasound. The 47-year-old male subject took 16 days 7 h 45 min to complete the route. He rode an average of 16.8 h/day. Neither maximal O2 uptake nor maximal power output changed pre- to post-TD. Measurement of total energy expenditure and dietary recall records suggested maintenance of energy balance, which was supported by the lack of change in body weight. The subject lost both appendicular and trunk fat mass and gained leg lean mass pre- to post-TD. Skeletal muscle mitochondrial and vascular endothelial function decreased pre- to post-TD. Overall, exercise performance was maintained despite reductions in muscle mitochondrial and vascular endothelial function post-TD, suggesting a metabolic reserve in our highly trained athlete.

Relationships Between Running Biomechanics and Femoral Articular Cartilage Thickness and Composition in Anterior Cruciate Ligament Reconstruction Patients.

BACKGROUND: Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear. OBJECTIVE: We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls. METHODS: Twenty patients with ACLR (time post-ACLR: 14.6 ± 6.1 months) and 20 matched controls participated in the study. A running session required both groups to run for 30 min at a self-selected speed. Before and after running, we measured femoral cartilage thickness via ultrasound imaging. A MRI session consisted of T2 mapping. RESULTS: The ACLR group showed longer T2 relaxation times in the medial femoral condyle at resting compared with the control group (central: 51.2 ± 16.6 vs. 34.9 ± 13.2 ms, p = 0.006; posterior: 50.2 ± 10.1 vs. 39.8 ± 7.4 ms, p = 0.006). Following the run, the ACLR group showed greater deformation in the medial femoral cartilage than the control group (0.03 ± 0.01 vs. 0.01 ± 0.01 cm, p = 0.001). Additionally, the ACLR group showed significant negative correlations between resting T2 relaxation time in the medial femoral condyle and vertical impulse (standardized regression coefficients = -0.99 and p = 0.004) during running. CONCLUSIONS: Our findings suggest that those who are between 6 and 24 months post-ACLR have degraded cartilage composition and their cartilage deforms more due to running vGRF.

Passive heat stress induces mitochondrial adaptations in skeletal muscle.

The mitochondria are central to skeletal muscle metabolic health. Impaired mitochondrial function is associated with various muscle pathologies, including insulin resistance and muscle atrophy. As a result, continuous efforts are made to find ways to improve mitochondrial health in the context of disuse and disease. While exercise is known to cause robust improvements in mitochondrial health, not all individuals are able to exercise. This creates a need for alternate interventions which elicit some of the same benefits as exercise. Passive heating (i.e., application of heat in the absence of muscle contractions) is one potential intervention which has been shown to increase mitochondrial enzyme content and activity, and to improve mitochondrial respiration. Associated with increases in mitochondrial content and/or function, passive heating can also improve insulin sensitivity in the context of type II diabetes and preserve muscle mass in the face of limb disuse. This area of research remains in its infancy, with many questions yet to be answered about how to maximize the benefits of passive heating and elucidate the mechanisms by which heat stress affects muscle mitochondria.

Utilizing Nonequilibrium Isotope Enrichments to Dramatically Increase Turnover Measurement Ranges in Single Biopsy Samples from Humans.

The synthesis of new proteins and the degradation of old proteins in vivo can be quantified in serial samples using metabolic isotope labeling to measure turnover. Because serial biopsies in humans are impractical, we set out to develop a method to calculate the turnover rates of proteins from single human biopsies. This method involved a new metabolic labeling approach and adjustments to the calculations used in previous work to calculate protein turnover. We demonstrate that using a nonequilibrium isotope enrichment strategy avoids the time dependent bias caused by variable lag in label delivery to different tissues observed in traditional metabolic labeling methods. Turnover rates are consistent for the same subject in biopsies from different labeling periods, and turnover rates calculated in this study are consistent with previously reported values. We also demonstrate that by measuring protein turnover we can determine where proteins are synthesized. In human subjects a significant difference in turnover rates differentiated proteins synthesized in the salivary glands versus those imported from the serum. We also provide a data analysis tool, DeuteRater-H, to calculate protein turnover using this nonequilibrium metabolic 2H2O method.

Localized Heat Therapy Improves Mitochondrial Respiratory Capacity but Not Fatty Acid Oxidation.

AIM: Mild heat stress can improve mitochondrial respiratory capacity in skeletal muscle. However, long-term heat interventions are scarce, and the effects of heat therapy need to be understood in the context of the adaptations which follow the more complex combination of stimuli from exercise training. The purpose of this work was to compare the effects of 6 weeks of localized heat therapy on human skeletal muscle mitochondria to single-leg interval training. METHODS: Thirty-five subjects were assigned to receive sham therapy, short-wave diathermy heat therapy, or single-leg interval exercise training, localized to the quadriceps muscles of the right leg. All interventions took place 3 times per week. Muscle biopsies were performed at baseline, and after 3 and 6 weeks of intervention. Mitochondrial respiratory capacity was assessed on permeabilized muscle fibers via high-resolution respirometry. RESULTS: The primary finding of this work was that heat therapy and exercise training significantly improved mitochondrial respiratory capacity by 24.8 ± 6.2% and 27.9 ± 8.7%, respectively (p < 0.05). Fatty acid oxidation and citrate synthase activity were also increased following exercise training by 29.5 ± 6.8% and 19.0 ± 7.4%, respectively (p < 0.05). However, contrary to our hypothesis, heat therapy did not increase fatty acid oxidation or citrate synthase activity. CONCLUSION: Six weeks of muscle-localized heat therapy significantly improves mitochondrial respiratory capacity, comparable to exercise training. However, unlike exercise, heat does not improve fatty acid oxidation capacity.

Passive muscle heating attenuates the decline in vascular function caused by limb disuse.

Limb disuse has profound negative consequences on both vascular and skeletal muscle health. The purpose of this investigation was to determine whether repeated application of passive heat, applied to the knee extensor muscles, could mitigate the detrimental effects of limb disuse on vascular function. This was a randomized, single-blinded placebo controlled trial. Twenty-one healthy volunteers (10 women, 11 men) underwent 10 days of unilateral lower limb immobilization and were randomized to receive either a daily 2 h sham (Imm) or heat treatment (Imm+H) using pulsed shortwave diathermy. Vascular function was assessed with Doppler ultrasound of the femoral artery and the passive leg movement technique. Biopsies of the vastus lateralis were also collected before and after the intervention. In Imm, femoral artery diameter (FAD) and PLM-induced hyperaemia (HYP) were reduced by 7.3% and 34.3%, respectively. Changes in both FAD (4% decrease; P = 0.0006) and HYP (7.8% increase; P = 0.003) were significantly attenuated in Imm+H. Vastus lateralis capillary density was not altered in either group. Immobilization significantly decreased expression of vascular endothelial growth factor (P = 0.006) and Akt (P = 0.001), and increased expression of angiopoietin 2 (P = 0.0004) over time, with no differences found between groups. Immobilization also upregulated elements associated with remodelling of the extracellular matrix, including matrix metalloproteinase 2 (P = 0.0046) and fibronectin (P = 0.0163), with no differences found between groups. In conclusion, limb immobilization impairs vascular endothelial function, but daily muscle heating via diathermy is sufficient to counteract this adverse effect. These are the first data to indicate that passive muscle heating mitigates disuse-induced vascular dysfunction. KEY POINTS: Limb disuse can be unavoidable for many of reasons (i.e. injury, bed rest, post-surgery), and can have significant adverse consequences for muscular and vascular health. We tested the hypothesis that declines in vascular function that result from lower limb immobilization could be mitigated by application of passive heat therapy. This report shows that 10 days of limb immobilization significantly decreases resistance artery diameter and vascular function, and that application of passive heat to the knee extensor muscle group each day for 2 h per day is sufficient to attenuate these declines. Additionally, muscle biopsy analyses showed that 10 days of heat therapy does not alter capillary density of the muscle, but upregulates multiple factors indicative of a vascular remodelling response. Our data demonstrate the utility of passive heat as a therapeutic tool to mitigate losses in lower limb vascular function that occur from disuse.

An altered response in macrophage phenotype following damage in aged human skeletal muscle: implications for skeletal muscle repair.

The purpose of this study was to test the hypothesis that macrophage polarization is altered in old compared to young skeletal muscle, possibly contributing to the poor satellite cell response observed in older muscle tissue. Muscle biopsies were collected prior to and at 3, 24, and 72 h following a muscle-damaging exercise in young and old individuals. Immunohistochemistry was used to measure i.m. macrophage content and phenotype, and cell culture experiments tested macrophage behavior and influence on primary myoblasts from older individuals. We found that macrophage infiltration was similar between groups at 24 (young: 3712 ± 2407 vs. old: 5035 ± 2978 cells/mm3) and 72 (young: 4326 ± 2622 vs. old: 5287 ± 2248 cells/mm3) hours postdamage, yet the proportion of macrophages that expressed the proinflammatory marker CD11b were markedly lower in the older subjects (young: 74.5 ± 15 vs. old: 52.6 ± 17%). This finding was coupled with a greater overall proportion of CD206+, anti-inflammatory macrophages in the old (group: P = 0.0005). We further demonstrate in vitro that proliferation, and in some cases differentiation, of old primary human myoblasts increase as much as 30% when exposed to a young macrophage-conditioned environment. Collectively, the data suggest that old macrophages appear less capable of adapting and maintaining inflammatory function, which may contribute to poor satellite cell activation and delayed recovery from muscle damage.-Sorensen, J. R., Kaluhiokalani, J. P., Hafen, P. S., Deyhle, M. R., Parcell, A. C., Hyldahl, R. D. An altered response in macrophage phenotype following damage in aged human skeletal muscle: implications for skeletal muscle repair.

Ketones Elicit Distinct Alterations in Adipose Mitochondrial Bioenergetics.

OBJECTIVE: The rampant growth of obesity worldwide has stimulated explosive research into human metabolism. Energy expenditure has been shown to be altered by diets differing in macronutrient composition, with low-carbohydrate, ketogenic diets eliciting a significant increase over other interventions. The central aim of this study was to explore the effects of the ketone ß-hydroxybutyrate (ßHB) on mitochondrial bioenergetics in adipose tissue. METHODS: We employed three distinct systems-namely, cell, rodent, and human models. Following exposure to elevated ßHB, we obtained adipose tissue to quantify mitochondrial function. RESULTS: In every model, ßHB robustly increased mitochondrial respiration, including an increase of roughly 91% in cultured adipocytes, 113% in rodent subcutaneous adipose tissue (SAT), and 128% in human SAT. However, this occurred without a commensurate increase in adipose ATP production. Furthermore, in cultured adipocytes and rodent adipose, we quantified and observed an increase in the gene expression involved in mitochondrial biogenesis and uncoupling status following ßHB exposure. CONCLUSIONS: In conclusion, ßHB increases mitochondrial respiration, but not ATP production, in mammalian adipocytes, indicating altered mitochondrial coupling. These findings may partly explain the increased metabolic rate evident in states of elevated ketones, and may facilitate the development of novel anti-obesity interventions.

Whole-Body Vibration as a Warm-up Before Exercise-Induced Muscle Damage on Symptoms of Delayed-Onset Muscle Soreness in Trained Subjects.

Magoffin, RD, Parcell, AC, Hyldahl, RD, Fellingham, GW, Hopkins, JT, and Feland, JB. Whole-body vibration as a warm-up before exercise-induced muscle damage on symptoms of delayed-onset muscle soreness in trained subjects. J Strength Cond Res 34(4): 1123-1132, 2020-There is no clear scientific evidence that whole-body vibration (WBV) used as a warm-up before performing eccentric exercise mitigates delayed-onset muscle soreness (DOMS) and speeds strength loss recovery. These benefits were observed primarily in nonresistance-trained individuals. The aim of this study was to determine whether WBV could mitigate soreness and expedite strength recovery for resistance-trained individuals when used as a warm-up before eccentric exercise. Thirty resistance-trained males completed 300 maximal eccentric contractions of the quadriceps after warming up with (WBV) or without (CON) WBV. Both CON and WBV experienced significant isometric (26.3 and 30.2%, respectively) and dynamic (50.9 and 46.4%, respectively) strength loss immediately after exercise. Isometric strength was significantly depressed after 24 hours in the CON group (8.2% p < 0.02), but not in the WBV group (5.9% p = 0.7). Isometric strength was no longer significantly depressed after 48 hours in the CON group (6.1% p < 0.07) or the WBV group (4.1% p = 0.20). Dynamic strength was significantly decreased in both the CON and WBV groups at 24 hours (17.7% p < 0.001 and 15.5% p < 0.001, respectively) and 48 hours (17.1% p < 0.01 and 13.6% p < 0.002), but only significant for the CON at 1 week after exercise (8.6% p = 0.05). Pain as measured by a visual analog scale was significant in both groups at 24 and 48 hours after exercise, but WBV experienced significantly less soreness than the CON group after 24 hours (28 vs. 46 mm p < 0.01, respectively) and 48 hours (38 vs. 50 mm p < 0.01). Pain pressure threshold increased significantly in both groups, but there was no difference between groups. These results suggest the use of WBV before eccentric exercise mildly mitigates DOMS in trained individuals. Application of WBV can function as a quick mode of warm-up before resistance training and can decrease pain perception from DOMS. This may be beneficial to athletes undergoing a heavy strength training phase where DOMS is likely.

Effects of Ice Massage Prior to an Iontophoresis Treatment Using Dexamethasone Sodium Phosphate.

CONTEXT: Low current intensity iontophoresis treatments have increased skin perfusion over 700% from baseline potentially altering drug clearance from or diffusion to the targeted area. OBJECTIVE: To determine the effects of a preceding 10-minute ice massage on subcutaneous dexamethasone sodium phosphate (Dex-P) concentration and skin perfusion during and after a 4-mA iontophoresis treatment. DESIGN: Controlled laboratory study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four participants (male = 12, female = 12; age = 25.6 [4.5] y, height = 173.9 [8.51] cm, mass = 76.11 [16.84] kg). INTERVENTION(S): Participants were randomly assigned into 2 groups: (1) pretreatment 10-minute ice massage and (2) no pretreatment ice massage. Treatment consisted of an 80-mA·minute (4 mA, 20 min) Dex-P iontophoresis treatment. Microdialysis probes (3 mm deep in the forearm) were used to assess Dex-P, dexamethasone (Dex), and its metabolite (Dex-Met) concentrations. Skin perfusion was measured using laser Doppler flowmetry. MAIN OUTCOME MEASURE(S): Microdialysis samples were collected at baseline, at conclusion of treatment, and every 20 minutes posttreatment for 60 minutes. Samples were analyzed to determine Dex-Total (Dex-Total = Dex-P + Dex + Dex-Met). Skin perfusion was calculated as a percentage change from baseline. A mixed-design analysis of variance was used to determine Dex-Total and skin perfusion difference between groups overtime. RESULTS: There was no difference between groups (P = .476), but [Dex-Total] significantly increased over the course of the iontophoresis and posttreatment time (P < .001). Dex-P was measured in 18 of 24 participants with a mean concentration of 0.67 (1.09) µg/mL. Skin perfusion was significantly greater in the no ice treatment group (P = .002). Peak skin perfusion reached 27.74% (47.49%) and 117.39% (103.45%) from baseline for the ice and no ice groups, respectively. CONCLUSIONS: Ice massage prior to iontophoresis does not alter the tissue [Dex-Total] even with less skin perfusion.

Mechanisms and Mediators of the Skeletal Muscle Repeated Bout Effect.

Skeletal muscle adapts to exercise-induced damage by orchestrating several but still poorly understood mechanisms that endow protection from subsequent damage. Known widely as the repeated bout effect, we propose that neural adaptations, alterations to muscle mechanical properties, structural remodeling of the extracellular matrix, and biochemical signaling work in concert to coordinate the protective adaptation.

Extracellular matrix remodeling and its contribution to protective adaptation following lengthening contractions in human muscle.

This study determined the contribution of extracellular matrix (ECM) remodeling to the protective adaptation of human skeletal muscle known as the repeated-bout effect (RBE). Muscle biopsies were obtained 3 hours, 2 days, and 27 days following an initial bout (B1) of lengthening contractions (LCs) and 2 days following a repeated bout (B2) in 2 separate studies. Biopsies from the nonexercised legs served as controls. In the first study, global transcriptomic analysis indicated widespread changes in ECM structural, deadhesive, and signaling transcripts, 3 hours following LC. To determine if ECM remodeling is involved in the RBE, we conducted a second study by use of a repeated-bout paradigm. TNC immunoreactivity increased 10.8-fold following B1, was attenuated following B2, and positively correlated with LC-induced strength loss (r(2) = 0.45; P = 0.009). Expression of collagen I, III, and IV (COL1A1, COL3A1, COL4A1) transcripts was unchanged early but increased 5.7 ± 2.5-, 3.2 ± 0.9-, and 2.1 ± 0.4-fold (P < 0.05), respectively, 27 days post-B1 and were unaffected by B2. Likewise, TGF-ß signaling demonstrated a delayed response following LC. Satellite cell content increased 80% (P < 0.05) 2 days post-B1 (P < 0.05), remained elevated 27 days post-B1, and was unaffected by B2. Collectively, the data suggest sequential ECM remodeling characterized by early deadhesion and delayed reconstructive activity that appear to contribute to the RBE.

Running decreases knee intra-articular cytokine and cartilage oligomeric matrix concentrations: a pilot study.

INTRODUCTION: Regular exercise protects against degenerative joint disorders, yet the mechanisms that underlie these benefits are poorly understood. Chronic, low-grade inflammation is widely implicated in the onset and progression of degenerative joint disease. PURPOSE: To examine the effect of running on knee intra-articular and circulating markers of inflammation and cartilage turnover in healthy men and women. METHODS: Six recreational runners completed a running (30 min) and control (unloaded for 30 min) session in a counterbalanced order. Synovial fluid (SF) and serum samples were taken before and after each session. Cytokine concentration was measured in SF and serum using a multiplexed cytokine magnetic bead array. Ground reaction forces were measured during the run. RESULTS: There were no changes in serum or SF cytokine concentration in the control condition. The cytokine GM-CSF decreased from 10.7 ± 9.8 to 6.2 ± 5.9 pg/ml pre- to post-run (p = 0.03). IL-15 showed a trend for decreasing concentration pre- (6.7 ± 7.5 pg/ml) to post-run (4.3 ± 2.7 pg/ml) (p = 0.06). Changes in IL-15 concentration negatively correlated with the mean number of foot strikes during the run (r 2 = 0.67; p = 0.047). The control condition induced a decrease in serum COMP and an increase in SF COMP, while conversely the run induced an increase in serum COMP and a decrease in SF COMP. Changes in serum and SF COMP pre- to post-intervention were inversely correlated (r 2 = 0.47; p = 0.01). CONCLUSIONS: Running appears to decrease knee intra-articular pro-inflammatory cytokine concentration and facilitates the movement of COMP from the joint space to the serum.

Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders.

Athletic Performance Decline Over the Life Span: Cross-Sectional and Longitudinal Analyses of Elite and Masters Track-and-Field Data.

PURPOSE: Loss of muscle power has a significant impact on mobility in geriatric populations, so this study sought to determine the extent and time course of performance decline in power-centric events throughout the life span via retrospective analyses of masters and elite track-and-field data. METHODS: Four track-and-field events were selected based on maximal power output: the 100-m dash, long jump, high jump, and triple jump. Elite and masters athlete data were gathered from the World Masters Outdoor Championships and the International Amateur Athletic Federation World Athletics Championships (17,945 individual results). Data were analyzed by fitting individual and group results to quadratic and linear models. RESULTS: Average age of peak performance in all events was 27.8 (0.8) years for men and 28.3 (0.8) years for women. Athlete performance decline best matched a linear model for the 5 years following peak performance (mean R2 = .68 [.20]) and for ages 35-60, but best matched a quadratic model for ages 60-90 and 35-90 (mean R2 = .75 [.12]). The average rate of decline for the masters data ages 35-60 ranged from 0.55% per year for men's 100-m dash to 1.04% per year for women's long jump. A significant age × sex interaction existed between men and women, with men declining faster throughout life in all events except the 100-m dash. CONCLUSIONS: Performance decline begins in the early 30s and is linear through middle age. This pattern of decline provides a basis for further research on power-decline pathophysiology and preventive measures starting in the 30s.

Common Markers of Muscle Damage Are Associated with Divergent Gene Expression Patterns after Eccentric Contractions.

PURPOSE: Unaccustomed eccentric (ECC) exercise evokes exercise-induced muscle damage (EIMD). Soreness, strength loss, and serum creatine kinase (CK) are often used to quantify EIMD severity. However, changes in these markers are not fully understood mechanistically. To test the hypothesis that muscle damage markers are associated with unique molecular processes, we correlated gene expression responses with variation in each marker post-ECC. METHODS: Vastus lateralis biopsies were collected from 35 young men 3 h post-ECC (10 sets of 10 maximal eccentric contractions; contralateral leg [CON] as control). Maximal isometric strength, soreness, and serum CK activity were assessed 24 h preexercise and every 24 h for 5 d post-ECC. Strength was also measured 10 min post-ECC. Over the 5 d after ECC, average peak strength loss was 51.5 ± 20%; average soreness increased from 0.9 ± 1.9 on a 100-mm visual analog scale to 39 ± 19; serum CK increased from 160 ± 130 to 1168 ± 3430 U·L -1 . Muscle RNA was used to generate gene expression profiles. Partek Genomics Suite correlated peak values of soreness, strength loss, and CK post-ECC with gene expression in ECC (relative to paired CON) using Pearson linear correlation ( P < 0.05) and repeated-measures ANOVA used to detect influence of ECC. RESULTS: After ECC, 2677 genes correlated with peak soreness, 3333 genes with peak strength loss, and 3077 genes with peak CK. Less than 1% overlap existed across all markers (16/9087). Unique genes included 2346 genes for peak soreness, 3032 genes for peak strength loss, and 2937 genes for peak CK. CONCLUSIONS: The largely unique molecular pathways associated with common indirect markers of EIMD indicate that each marker of "damage" represents unique mechanistic processes.

NF-KB activity functions in primary pericytes in a cell- and non-cell-autonomous manner to affect myotube formation.

INTRODUCTION: Skeletal muscle regeneration following damage relies on proliferation and differentiation of muscle precursor cells (MPCs). We recently observed increased NF-kB activity in vascular-associated muscle resident pericytes following muscle damage in humans. We determined how altered NF-kB activity in human primary pericytes (HPPs) affects their myogenic differentiation (cell-autonomous effects), as well as proliferation and differentiation of co-cultured MPCs (non-cell-autonomous effects). METHODS: HPPs were transfected with vectors that increased or decreased NF-kB activity. Transfected HPPs were co-cultured with C2 C12 myoblasts under differentiation conditions, and HPP fusion to myotubes was measured. We also co-cultured HPPs with C2 C12 myoblasts and measured proliferation and myotube formation. RESULTS: Inhibition of NF-kB activity increased HPP fusion to C2 C12 myotubes. Moreover, enhanced NF-kB activity in HPPs suppressed differentiation and enhanced proliferation of co-cultured myoblasts. CONCLUSIONS: NF-kB activity acts cell-autonomously to inhibit HPP myogenic differentiation and non-cell-autonomously to promote MPC proliferation and suppress MPC differentiation in vitro.

Activation of nuclear factor-κB following muscle eccentric contractions in humans is localized primarily to skeletal muscle-residing pericytes.

Limited data exist on the molecular mechanisms that govern skeletal muscle regeneration in humans. This study characterized the early molecular alterations in humans to eccentric contractions (ECs), a stimulus known to induce a muscle regenerative response. Thirty-five subjects completed 100 ECs of the knee extensors with 1 leg, and muscle biopsies were taken from both legs 3 h post-EC. The sample from the non-EC leg served as the control. We first conducted a well-powered transcriptomic screen and network analysis. Our screen identified significant changes in several transcripts with functions relating to inflammation, cell growth, and proliferation. Network analysis then identified the transcription factor NF-κB as a key molecular element affected by ECs. A transcription factor ELISA, using nuclear extracts from EC and control muscle samples, showed a 1.6-fold increase in NF-κB DNA binding activity following ECs. Immunohistochemical experiments localized the majority of NF-κB-positive nuclei to cells in the interstitium, which stained positive for the pericyte markers NG2 proteoglycan and alkaline phosphatase. Our results provide the first evidence of NF-κB activation in human muscle following ECs and suggest a novel role for muscle residing pericytes in the early adaptive response to ECs.