Peripheral quantitative computed tomography is a valid imaging technique for tracking changes in skeletal muscle cross-sectional area.

Peripheral quantitative computed tomography (pQCT) has recently expanded to quantifying skeletal muscle, however its validity to determine muscle cross-sectional area (mCSA) compared to magnetic resonance imaging (MRI) is unknown. Eleven male participants (age: 22 ± 3 y) underwent pQCT and MRI dual-leg mid-thigh imaging before (PRE) and after (POST) 6 weeks of resistance training for quantification of mid-thigh mCSA and change in mCSA. mCSA agreement at both time points and absolute change in mCSA across time was assessed using Bland-Altman plots for mean bias and 95% limits of agreement (LOA), as well as Lin's concordance correlation coefficients (CCC). Both pQCT and MRI mCSA increased following 6 weeks of resistance training (∆mCSApQCT: 6.7 ± 5.4 cm2, p < 0.001; ∆mCSAMRI: 6.0 ± 6.4 cm2, p < 0.001). Importantly, the change in mCSA was not different between methods (p = 0.39). Bland-Altman analysis revealed a small mean bias (1.10 cm2, LOA: -6.09, 8.29 cm2) where pQCT tended to overestimate mCSA relative to MRI when comparing images at a single time point. Concordance between pQCT and MRI mCSA at PRE and POST was excellent yielding a CCC of 0.982. For detecting changes in mCSA, Bland-Altman analysis revealed excellent agreement between pQCT and MRI (mean bias: -0.73 cm2, LOA: -8.37, 6.91 cm2). Finally, there was excellent concordance between pQCT and MRI mCSA change scores (CCC = 0.779). Relative to MRI, pQCT imaging is a valid technique for measuring both mid-thigh mCSA at a single time point and mCSA changes following a resistance training intervention.

Resistance training diminishes mitochondrial adaptations to subsequent endurance training in healthy untrained men.

We investigated the effects of performing a period of resistance training (RT) on the performance and molecular adaptations to a subsequent period of endurance training (ET). Twenty-five young adults were divided into an RT+ET group (n = 13), which underwent 7 weeks of RT followed by 7 weeks of ET, and an ET-only group (n = 12), which performed 7 weeks of ET. Body composition, endurance performance and muscle biopsies were collected before RT (T1, baseline for RT+ET), before ET (T2, after RT for RT+ET and baseline for ET) and after ET (T3). Immunohistochemistry was performed to determine fibre cross-sectional area (fCSA), myonuclear content, myonuclear domain size, satellite cell number and mitochondrial content. Western blots were used to quantify markers of mitochondrial remodelling. Citrate synthase activity and markers of ribosome content were also investigated. RT improved body composition and strength, increased vastus lateralis thickness, mixed and type II fCSA, myonuclear number, markers of ribosome content, and satellite cell content (P < 0.050). In response to ET, both groups similarly decreased body fat percentage (P < 0.0001) and improved endurance performance (e.g. V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ , and speed at which the onset of blood lactate accumulation occurred, P < 0.0001). Levels of mitochondrial complexes I-IV in the ET-only group increased 32-66%, while those in the RT+ET group increased 1-11% (time, P < 0.050). Additionally, mixed fibre relative mitochondrial content increased 15% in the ET-only group but decreased 13% in the RT+ET group (interaction, P = 0.043). In conclusion, RT performed prior to ET had no additional benefits to ET adaptations. Moreover, prior RT seemed to impair mitochondrial adaptations to ET. KEY POINTS: Resistance training is largely underappreciated as a method to improve endurance performance, despite reports showing it may improve mitochondrial function. Although several concurrent training studies are available, in this study we investigated the effects of performing a period of resistance training on the performance and molecular adaptations to subsequent endurance training. Prior resistance training did not improve endurance performance and impaired most mitochondrial adaptations to subsequent endurance training, but this effect may have been a result of detraining from resistance training.

The effects of resistance training to near failure on strength, hypertrophy, and motor unit adaptations in previously trained adults.

Limited research exists examining how resistance training to failure affects applied outcomes and single motor unit characteristics in previously trained individuals. Herein, resistance-trained adults (24 ± 3 years old, self-reported resistance training experience was 6 ± 4 years, 11 men and 8 women) were randomly assigned to either a low-repetitions-in-reserve (RIR; i.e., training near failure, n = 10) or high-RIR (i.e., not training near failure, n = 9) group. All participants implemented progressive overload during 5 weeks where low-RIR performed squat, bench press, and deadlift twice weekly and were instructed to end each training set with 0-1 RIR. high-RIR performed identical training except for being instructed to maintain 4-6 RIR after each set. During week 6, participants performed a reduced volume-load. The following were assessed prior to and following the intervention: (i) vastus lateralis (VL) muscle cross-sectional area (mCSA) at multiple sites; (ii) squat, bench press, and deadlift one-repetition maximums (1RMs); and (iii) maximal isometric knee extensor torque and VL motor unit firing rates during an 80% maximal voluntary contraction. Although RIR was lower in the low- versus high-RIR group during the intervention (p < 0.001), total training volume did not significantly differ between groups (p = 0.222). There were main effects of time for squat, bench press, and deadlift 1RMs (all p-values < 0.05), but no significant condition × time interactions existed for these or proximal/middle/distal VL mCSA data. There were significant interactions for the slope and y-intercept of the motor unit mean firing rate versus recruitment threshold relationship. Post hoc analyses indicated low-RIR group slope values decreased and y-intercept values increased after training suggesting low-RIR training increased lower-threshold motor unit firing rates. This study provides insight into how resistance training in proximity to failure affects strength, hypertrophy, and single motor unit characteristics, and may inform those who aim to program for resistance-trained individuals.

Resistance Training Diminishes Mitochondrial Adaptations to Subsequent Endurance Training.

We investigated the effects of performing a period of resistance training (RT) on the performance and molecular adaptations to a subsequent period of endurance training (ET). Twenty-five young adults were divided into RT+ET (n=13), which underwent seven weeks of RT followed by seven weeks of ET, and ET-only (n=12), which performed seven weeks of ET. Body composition, endurance performance, and muscle biopsies were collected before RT (T1, baseline for RT+ET), before ET (T2, post RT for RT+ET and baseline for ET), and after ET (T3). Immunohistochemistry was performed to determine fiber cross-sectional area (fCSA), myonuclear content, myonuclear domain size, satellite cell number, and mitochondrial content. Western blots were used to quantify markers of mitochondrial remodeling. Citrate synthase activity and markers of ribosome content were also investigated. Resistance training improved body composition and strength, increased vastus lateralis thickness, mixed and type II fCSA, myonuclear number, markers of ribosome content, and satellite cell content (p<0.050). In response to ET, both groups similarly decreased body fat percentage and improved endurance performance (e.g., VO 2 max, and speed at which the onset of blood lactate accumulation occurred during the VO 2 max test). Levels of mitochondrial complexes I-IV in the ET-only group increased 32-66%, while the RT+ET group increased 1-11%. Additionally, mixed fiber relative mitochondrial content increased 15% in the ET-only group but decreased 13% in the RT+ET group. In conclusion, RT performed prior to ET had no additional benefits to ET adaptations. Moreover, prior RT seemed to impair mitochondrial adaptations to ET. KEY POINTS SUMMARY: Resistance training is largely underappreciated as a method to improve endurance performance, despite reports showing it may improve mitochondrial function.Although several concurrent training studies are available, in this study we investigated the effects of performing a period resistance training on the performance and molecular adaptations to subsequent endurance training.Prior resistance training did not improve endurance performance and impaired most mitochondrial adaptations to subsequent endurance training, but that seemed to be a result of detraining from resistance training.

Extracellular matrix content and remodeling markers do not differ in college-aged men classified as higher and lower responders to resistance training.

We determined if skeletal muscle extracellular matrix (ECM) content and remodeling markers adapted with resistance training or were associated with hypertrophic outcomes. Thirty-eight untrained males (21 ± 3 yr) participated in whole body resistance training (10 wk, 2 × weekly). Participants completed testing [ultrasound, peripheral quantitative computed tomography (pQCT)] and donated a vastus lateralis (VL) biopsy 1 wk before training and 72 h following the last training bout. Higher responders (HR, n = 10) and lower responders (LR, n = 10) were stratified based on a composite score considering changes in pQCT-derived mid-thigh cross-sectional area (mCSA), ultrasound-derived VL thickness, and mean fiber cross-sectional area (fCSA). In all participants, training reduced matrix metalloprotease (MMP)-14 protein (P < 0.001) and increased satellite cell abundance (P < 0.001); however, VL fascial thickness, ECM protein content per myofiber, MMP-2/-9 protein content, tissue inhibitor of metalloproteinase (TIMP)-1/-2 protein content, collagen-1/-4 protein content, macrophage abundance, or fibroadipogenic progenitor cell abundance were not altered. Regarding responder analysis, MMP-14 exhibited an interaction (P = 0.007), and post hoc analysis revealed higher protein content in HR versus LR before training (P = 0.026) and a significant decrease from pre to posttraining in HR only (P = 0.002). In summary, basal skeletal muscle ECM markers are minimally affected with 10 wk of resistance training, and these findings could be related to not capturing more dynamic alterations in the assayed markers earlier in training. However, the downregulation in MMP-14 in college-aged men classified as HR is a novel finding and warrants continued investigation, and further research is needed to delineate muscle connective tissue strength attributes between HR and LR.NEW & NOTEWORTHY Although past studies have examined aspects of extracellular matrix remodeling in relation to mechanical overload or resistance training, this study serves to expand our knowledge on a multitude of extracellular matrix markers and whether these markers adapt to resistance training or are associated with differential hypertrophic responses.

Molecular predictors of resistance training outcomes in young untrained female adults.

We sought to determine if the myofibrillar protein synthetic (MyoPS) response to a naïve resistance exercise (RE) bout, or chronic changes in satellite cell number and muscle ribosome content, were associated with hypertrophic outcomes in females or differed in those who classified as higher (HR) or lower (LR) responders to resistance training (RT). Thirty-four untrained college-aged females (23.4 ± 3.4 kg/m2) completed a 10-wk RT protocol (twice weekly). Body composition and leg imaging assessments, a right leg vastus lateralis biopsy, and strength testing occurred before and following the intervention. A composite score, which included changes in whole body lean/soft tissue mass (LSTM), vastus lateralis (VL) muscle cross-sectional area (mCSA), midthigh mCSA, and deadlift strength, was used to delineate upper and lower HR (n = 8) and LR (n = 8) quartiles. In all participants, training significantly (P < 0.05) increased LSTM, VL mCSA, midthigh mCSA, deadlift strength, mean muscle fiber cross-sectional area, satellite cell abundance, and myonuclear number. Increases in LSTM (P < 0.001), VL mCSA (P < 0.001), midthigh mCSA (P < 0.001), and deadlift strength (P = 0.001) were greater in HR vs. LR. The first-bout 24-hour MyoPS response was similar between HR and LR (P = 0.367). While no significant responder × time interaction existed for muscle total RNA concentrations (i.e., ribosome content) (P = 0.888), satellite cell abundance increased in HR (P = 0.026) but not LR (P = 0.628). Pretraining LSTM (P = 0.010), VL mCSA (P = 0.028), and midthigh mCSA (P < 0.001) were also greater in HR vs. LR. Female participants with an enhanced satellite cell response to RT, and more muscle mass before RT, exhibited favorable resistance training adaptations.NEW & NOTEWORTHY This study continues to delineate muscle biology differences between lower and higher responders to resistance training and is unique in that a female population was interrogated. As has been reported in prior studies, increases in satellite cell numbers are related to positive responses to resistance training. Satellite cell responsivity, rather than changes in muscle ribosome content per milligrams of tissue, may be a more important factor in delineating resistance-training responses in women.

Skeletal Muscle DNA Methylation and mRNA Responses to a Bout of Higher versus Lower Load Resistance Exercise in Previously Trained Men.

We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 h, and 6 h after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p < 0.001), although total training volume (sets × reps × load) was not significantly different between bouts (p = 0.571). Regardless of bout, more CpG site methylation changes were observed at 3 h versus 6 h post exercise (239,951 versus 12,419, respectively; p < 0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3 h and 6 h following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3 h versus 6 h following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 h following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 h following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to "Focal adhesion," "MAPK signaling," and "PI3K-Akt signaling" were significantly affected at the 3 h and 6 h time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts.

Changes in vastus lateralis fibre cross-sectional area, pennation angle and fascicle length do not predict changes in muscle cross-sectional area.

NEW FINDINGS: What is the central question of this study? Do changes in myofibre cross-sectional area, pennation angle and fascicle length predict vastus lateralis whole-muscle cross-sectional area changes following resistance training? What is the main finding and its importance? Changes in vastus lateralis mean myofibre cross-sectional area, fascicle length and pennation angle following a period of resistance training did not collectively predict changes in whole-muscle cross-sectional area. Despite the limited sample size in this study, these data reiterate that it remains difficult to generalize the morphological adaptations that predominantly drive tissue-level vastus lateralis muscle hypertrophy. ABSTRACT: Myofibre hypertrophy during resistance training (RT) poorly associates with tissue-level surrogates of hypertrophy. However, it is underappreciated that, in pennate muscle, changes in myofibre cross-sectional area (fCSA), fascicle length (Lf ) and pennation angle (PA) likely coordinate changes in whole-muscle cross-sectional area (mCSA). Therefore, we determined if changes in fCSA, PA and Lf predicted vastus lateralis (VL) mCSA changes following RT. Thirteen untrained college-aged males (23 ± 4 years old, 25.4 ± 5.2 kg/m2 ) completed 7 weeks of full-body RT (twice weekly). Right leg VL ultrasound images and biopsies were obtained prior to (PRE) and 72 h following (POST) the last training bout. Regression was used to assess if training-induced changes in mean fCSA, PA and Lf predicted VL mCSA changes. Correlations were also performed between PRE-to-POST changes in obtained variables. Mean fCSA (+18%), PA (+8%) and mCSA (+22%) increased following RT (P < 0.05), but not Lf (0.1%, P = 0.772). Changes in fCSA, Lf and PA did not collectively predict changes in mCSA (R2 = 0.282, adjusted R2 = 0.013, F3,8  = 1.050, P = 0.422). Moderate negative correlations existed for percentage changes in PA and Lf (r = -0.548, P = 0.052) and changes in fCSA and Lf (r = -0.649, P = 0.022), and all other associations were weak (|r| < 0.500). Although increases in mean fCSA, PA and VL mCSA were observed, inter-individual responses for each variable and limitations for each technique make it difficult to generalize the morphological adaptations that predominantly drive tissue-level VL muscle hypertrophy. However, the small subject pool is a significant limitation, and more research in this area is needed.

Comparisons between skeletal muscle imaging techniques and histology in tracking midthigh hypertrophic adaptations following 10 wk of resistance training.

This study had two aims. Aim1 was to determine the agreement between midthigh vastus lateralis (VL) cross-sectional area measured by ultrasound (mCSAUS) versus magnetic resonance imaging (mCSAMRI) at a single time point, and the ability of each to detect hypertrophic changes. Aim2 was to assess the relationships between pre- and posttraining changes in thigh lean mass determined by dual-energy X-ray absorptiometry (DXA), VL mCSAUS, ultrasound-determined VL thickness (VLThick), and VL mean myofiber cross-sectional area (fCSA) with changes in VL mCSAMRI. Twelve untrained males (age: 20 ± 1 yr, BMI: 26.9 ± 5.4 kg/m2; n = 12) engaged in a 10-wk resistance training program (2×/week) where right midthigh images and VL biopsies were obtained before and 72 h following the last training bout. Participants' VL mCSAMRI (P = 0.005), DXA thigh lean mass (P = 0.015), and VLThick (P = 0.001) increased following training, whereas VL mCSAUS and fCSA did not. For Aim1, mCSAUS demonstrated excellent concordance [concordance correlation coefficients (CCC) = 0.830] with mCSAMRI, albeit mCSAUS values were systematically lower compared with mCSAMRI (mean bias: -2.29 cm2). In addition, PRE-to-POST VL mCSA changes between techniques exhibited good agreement (CCC = 0.700; mean bias: -1.08 cm2). For Aim2, moderate, positive correlations existed for pre-to-post changes in VL mCSAMRI and DXA thigh lean mass (r = 0.580, P = 0.048), mCSAUS (r = 0.622, P = 0.031), and VLThick (r = 0.520, P = 0.080). A moderate, negative correlation existed between mCSAMRI and fCSA (r = -0.569, P = 0.054). Our findings have multiple implications: 1) resistance training-induced hypertrophy was dependent on the quantification method, 2) ultrasound-determined mCSA shows good agreement with MRI, and 3) tissue-level changes poorly agreed with mean fCSA changes and this requires further research.NEW & NOTEWORTHY This is the first study to comprehensively examine how different midthigh muscle imaging techniques and histology compare with one another in participants that performed 10 weeks of resistance training. Our study suggests that histology results show poor agreement with results yielded from other common muscle imaging techniques, and researchers should be aware of this limitation.

Translational Significance of the LINE-1 Jumping Gene in Skeletal Muscle.

Retrotransposons are gene segments that proliferate in the genome, and the Long INterspersed Element 1 (LINE-1 or L1) retrotransposon is active in humans. Although older mammals show enhanced skeletal muscle L1 expression, exercise generally reverses this trend. We hypothesize skeletal muscle L1 expression influences muscle physiology, and additional innovative investigations are needed to confirm this hypothesis.

Exploring the Effects of Six Weeks of Resistance Training on the Fecal Microbiome of Older Adult Males: Secondary Analysis of a Peanut Protein Supplemented Randomized Controlled Trial.

The bacteria inhabiting the gastrointestinal tract contribute to numerous host functions and can be altered by lifestyle factors. We aimed to determine whether a 6-week training intervention altered fecal microbiome diversity and/or function in older males. Fecal samples were collected prior to and following a 6-week twice-weekly supervised resistance training intervention in 14 older Caucasian males (65 ± 10 years, 28.5 ± 3.2 kg/m2) with minimal prior training experience. Participants were randomized to receive a daily defatted peanut powder supplement providing 30 g protein (n = 8) or no supplement (n = 6) during the intervention. Bacterial DNA was isolated from pre-and post-training fecal samples, and taxa were identified using sequencing to amplify the variable region 4 (V4) of the 16S ribosomal RNA gene. Training significantly increased whole-body and lower-body lean mass (determined by dual energy X-ray absorptiometry) as well as leg extensor strength (p < 0.05) with no differences between intervention groups. Overall composition of the microbiome and a priori selected taxa were not significantly altered with training. However, MetaCYC pathway analysis indicated that metabolic capacity of the microbiome to produce mucin increased (p = 0.047); the tight junction protein, zonulin, was measured in serum and non-significantly decreased after training (p = 0.062). Our data suggest that resistance training may improve intestinal barrier integrity in older Caucasian males; further investigation is warranted.

Effects of High-Volume Versus High-Load Resistance Training on Skeletal Muscle Growth and Molecular Adaptations.

We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p = 0.046), where HV increased this metric from PRE to POST (+3.2%, p = 0.018) whereas HL training did not (-0.1%, p = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p = 0.032; HV < HL at POST and POSTPR, p < 0.025 for each). Six-week integrated non-myofibrillar protein synthesis (iNon-MyoPS) rates were also higher in the HV versus HL condition, while no difference between conditions existed for iMyoPS rates. No interactions existed for other strength, VL morphology variables, or the relative abundances of major muscle proteins. Compared to HL training, 6 weeks of HV training in previously trained men optimizes VL hypertrophy in lieu of enhanced iNon-MyoPS rates, and this warrants future research.

Whey Protein Supplementation Effects on Body Composition, Performance, and Blood Biomarkers During Army Initial Entry Training.

This study assesses if a lower dose of whey protein can provide similar benefits to those shown in previous work supplementing Army Initial Entry Training (IET) Soldiers with two servings of whey protein (WP) per day. Eighty-one soldiers consumed one WP or a calorie matched carbohydrate (CHO) serving/day during IET (WP: n = 39, height = 173 ± 8 cm, body mass = 76.8 ± 12.8 kg, age = 21 ± 3 years; CHO: n = 42, 175 ± 8 cm, 77.8 ± 15.3 kg, 23 ± 4 years). Physical performance (push-ups, sit-ups, and a two-mile run) was assessed during weeks two and eight. All other measures (dietary intake, body composition, blood biomarkers) at weeks one and nine. There was a significant group difference for fat mass (p = 0.044) as WP lost 2.1 ± 2.9 kg and had a moderate effect size (Cohen's d: -0.24), whereas the CHO group lost 0.9 ± 2.5 kg and had only a small effect size (d: -0.1). There was no significant group-by-time interaction on fat-free mass (p = 0.069). WP gained 1.2 ± 2.4 (d: 0.1) and CHO gained 0.1 ± 3 (d: 0) kg of FFM on average. There was a significant group by week 1-fat free mass interaction (p = 0.003) indicating individuals with higher initial fat-free mass benefitted more from WP. There were no group differences for push-up (p = 0.514), sit-up (p = 0.429) or run (p = 0.313) performance. For all biomarkers there was a significant effect of time as testosterone (p < 0.01), testosterone to cortisol ratio (p = 0.39), and IGF-1 (p < 0.01) increased across training and cortisol (p = 0.04) and IL-6 (p < 0.01) decreased. There were no differences in groups across IET for any of the biomarkers. We conclude one WP serving is beneficial for FM and for FFM in soldiers with high baseline FFM but may not significantly alter biomarker response or physical performance of IET soldiers who have high relative dietary protein intakes.

Effects of Peanut Protein Supplementation on Resistance Training Adaptations in Younger Adults.

Protein supplementation is a commonly employed strategy to enhance resistance training adaptations. However, little research to date has examined if peanut protein supplementation is effective in this regard. Thus, we sought to determine if peanut protein supplementation (PP; 75 total g/d of powder providing 30 g/d protein, >9.2 g/d essential amino acids, ~315 kcal/d) affected resistance training adaptations in college-aged adults. Forty-seven college-aged adults (n = 34 females, n = 13 males) with minimal prior training experience were randomly assigned to a PP group (n = 18 females, n = 5 males) or a non-supplement group (CTL; n = 16 females, n = 8 males) (ClinicalTrials.gov trial registration NCT04707963; registered 13 January 2021). Body composition and strength variables were obtained prior to the intervention (PRE). Participants then completed 10 weeks of full-body resistance training (twice weekly) and PP participants consumed their supplement daily. POST measures were obtained 72 h following the last training bout and were identical to PRE testing measures. Muscle biopsies were also obtained at PRE, 24 h following the first exercise bout, and at POST. The first two biopsy time points were used to determine myofibrillar protein synthesis (MyoPS) rates in response to a naïve training bout with or without PP, and the PRE and POST biopsies were used to determine muscle fiber adaptations in females only. Dependent variables were analyzed in males and females separately using two-way (supplement × time) repeated measures ANOVAs, unless otherwise stated. The 24-h integrated MyoPS response to the first naïve training bout was similar between PP and CTL participants (dependent samples t-test p = 0.759 for females, p = 0.912 for males). For males, the only significant supplement × time interactions were for DXA-derived fat mass (interaction p = 0.034) and knee extensor peak torque (interaction p = 0.010); these variables significantly increased in the CTL group (p < 0.05), but not the PP group. For females, no significant supplement × time interactions existed, although interactions for whole body lean tissue mass (p = 0.088) and vastus lateralis thickness (p = 0.099) approached significance and magnitude increases in these characteristics favored the PP versus CTL group. In summary, this is the second study to determine the effects of PP supplementation on resistance training adaptations. While PP supplementation did not significantly enhance training adaptations, the aforementioned trends in females, the limited n-size in males, and this being the second PP supplementation study warrant more research to determine if different PP dosing strategies are more effective than the current approach.

Myofibril and Mitochondrial Area Changes in Type I and II Fibers Following 10 Weeks of Resistance Training in Previously Untrained Men.

Resistance training increases muscle fiber hypertrophy, but the morphological adaptations that occur within muscle fibers remain largely unresolved. Fifteen males with minimal training experience (24±4years, 23.9±3.1kg/m2 body mass index) performed 10weeks of conventional, full-body resistance training (2× weekly). Body composition, the radiological density of the vastus lateralis muscle using peripheral quantitative computed tomography (pQCT), and vastus lateralis muscle biopsies were obtained 1week prior to and 72h following the last training bout. Quantification of myofibril and mitochondrial areas in type I (positive for MyHC I) and II (positive for MyHC IIa/IIx) fibers was performed using immunohistochemistry (IHC) techniques. Relative myosin heavy chain and actin protein abundances per wet muscle weight as well as citrate synthase (CS) activity assays were also obtained on tissue lysates. Training increased whole-body lean mass, mid-thigh muscle cross-sectional area, mean and type II fiber cross-sectional areas (fCSA), and maximal strength values for leg press, bench press, and deadlift (p<0.05). The intracellular area occupied by myofibrils in type I or II fibers was not altered with training, suggesting a proportional expansion of myofibrils with fCSA increases. However, our histological analysis was unable to differentiate whether increases in myofibril number or girth occurred. Relative myosin heavy chain and actin protein abundances also did not change with training. IHC indicated training increased mitochondrial areas in both fiber types (p=0.018), albeit CS activity levels remained unaltered with training suggesting a discordance between these assays. Interestingly, although pQCT-derived muscle density increased with training (p=0.036), suggestive of myofibril packing, a positive association existed between training-induced changes in this metric and changes in mean fiber myofibril area (r=0.600, p=0.018). To summarize, our data imply that shorter-term resistance training promotes a proportional expansion of the area occupied by myofibrils and a disproportional expansion of the area occupied by mitochondria in type I and II fibers. Additionally, IHC and biochemical techniques should be viewed independently from one another given the lack of agreement between the variables assessed herein. Finally, the pQCT may be a viable tool to non-invasively track morphological changes (specifically myofibril density) in muscle tissue.

Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities.

Skeletal muscle adaptations to resistance and endurance training include increased ribosome and mitochondrial biogenesis, respectively. Such adaptations are believed to contribute to the notable increases in hypertrophy and aerobic capacity observed with each exercise mode. Data from multiple studies suggest the existence of a competition between ribosome and mitochondrial biogenesis, in which the first adaptation is prioritized with resistance training while the latter is prioritized with endurance training. In addition, reports have shown an interference effect when both exercise modes are performed concurrently. This prioritization/interference may be due to the interplay between the 5' AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) signaling cascades and/or the high skeletal muscle energy requirements for the synthesis and maintenance of cellular organelles. Negative associations between ribosomal DNA and mitochondrial DNA copy number in human blood cells also provide evidence of potential competition in skeletal muscle. However, several lines of evidence suggest that ribosome and mitochondrial biogenesis can occur simultaneously in response to different types of exercise and that the AMPK-mTORC1 interaction is more complex than initially thought. The purpose of this review is to provide in-depth discussions of these topics. We discuss whether a curious competition between mitochondrial and ribosome biogenesis exists and show the available evidence both in favor and against it. Finally, we provide future research avenues in this area of exercise physiology.

Resistance training rejuvenates the mitochondrial methylome in aged human skeletal muscle.

Resistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Biochemical assays were also performed, and older male data were compared to younger trained males (22 ± 2 y.o., n = 7, n = 6 Caucasian & n = 1 African American). RT increased whole-body lean tissue mass (p = .017), VL thickness (p = .012), and knee extensor torque (p = .029) in older males. RT also affected the mtDNA methylome, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p < .05). Several mtDNA sites presented a more "youthful" signature in older males after RT in comparison to younger males. The 1.12 kilobase mtDNA D-loop/control region, which regulates replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and complex III/IV protein levels were also observed (p < .05). While limited to a shorter-term intervention, this is the first evidence showing that RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT evokes mitochondrial methylome profiles to mimic younger men. The significance of these findings relative to broader RT-induced epigenetic changes needs to be elucidated.

Effects of 12-Week Multivitamin and Omega-3 Supplementation on Micronutrient Levels and Red Blood Cell Fatty Acids in Pre-menopausal Women.

The purpose of this study was to validate the efficacy of a customized vitamin-mineral supplement on blood biomarkers in pre-menopausal females. Women (21-40 years old) who were apparently healthy were recruited from the local community (ClinicalTrials.gov trial registration NCT03828097). Pretesting (PRE) occurred in the morning 5 ± 2 days following each participant's menses and involved a fasted blood draw, body mass assessment, and blood pressure assessment. Participants were then randomly assigned in a double-blinded fashion to either the multivitamins (MV) (n = 43) or placebo group (n = 51). Participants consumed two capsules per day with breakfast for 12 weeks. Following the trial, participants reported to the laboratory for POST assessments, which replicated PRE procedures. Red blood cell fatty acid and serum micronutrient analyses were performed in a blinded fashion at hematology laboratories. A group × time interaction was observed for serum vitamin D levels (p < 0.001). MV increased levels from PRE to POST (+43.7%, p < 0.001), whereas no change occurred in the placebo group. Additionally, 78% of MV participants at PRE exhibited inadequate vitamin D levels (<40 ng/dl), whereas only 30% exhibited levels below this threshold at POST. An interaction was also observed for serum folate levels (p < 0.001). MV increased serum folate from PRE to POST (p < 0.001), whereas no change occurred in the placebo group. Red blood cell omega-3 fatty acid content increased from PRE to POST in the MV group (p < 0.001) and placebo group (p < 0.05), although POST values were greater in the MV group (p < 0.001). An interaction was observed for serum HDL cholesterol levels (p = 0.047), and a non-significant increase in this variable from PRE to POST occurred in the MV group (p = 0.060). Four-day food recalls indicated MV increased intake of omega-3 fatty acids, vitamin D, folate, and other micronutrients. In summary, MV supplementation increased serum vitamin D, serum folate, and red blood cell omega-3 fatty acid levels. However, these data are limited to healthy females, and more research is needed to examine if MV can affect metabolic disturbances in individuals with micronutrient deficiencies.

Molecular Differences in Skeletal Muscle After 1 Week of Active vs. Passive Recovery From High-Volume Resistance Training.

ABSTRACT: Vann, CG, Haun, CT, Osburn, SC, Romero, MA, Roberson, PA, Mumford, PW, Mobley, CB, Holmes, HM, Fox, CD, Young, KC, and Roberts, MD. Molecular differences in skeletal muscle after 1 week of active vs. passive recovery from high-volume resistance training. J Strength Cond Res 35(8): 2102-2113, 2021-Numerous studies have evaluated how deloading after resistance training (RT) affects strength and power outcomes. However, the molecular adaptations that occur after deload periods remain understudied. Trained, college-aged men (n = 30) performed 6 weeks of whole-body RT starting at 10 sets of 10 repetitions per exercise per week and finishing at 32 sets of 10 repetitions per exercise per week. After this period, subjects performed either active (AR; n = 16) or passive recovery (PR; n = 14) for 1 week where AR completed ∼15% of the week 6 training volume and PR ceased training. Variables related to body composition and recovery examined before RT (PRE), after 6 weeks of RT (POST), and after the 1-week recovery period (DL). Vastus lateralis (VL) muscle biopsies and blood samples were collected at each timepoint, and various biochemical and histological assays were performed. Group × time interactions (p < 0.05) existed for skeletal muscle myosin heavy chain (MHC)-IIa mRNA (AR > PR at POST and DL) and 20S proteasome activity (post-hoc tests revealed no significance in groups over time). Time effects (P < 0.05) existed for total mood disturbance and serum creatine kinase and mechano growth factor mRNA (POST > PRE &D L), VL pressure to pain threshold and MHC-IIx mRNA (PRE&DL > POST), Atrogin-1 and MuRF-1 mRNA (PRE < POST < DL), MHC-I mRNA (PRE < POST & DL), myostatin mRNA (PRE & POST < DL), and mechanistic target of rapamycin (PRE > POST & DL). No interactions or time effects were observed for barbell squat velocity, various hormones, histological metrics, polyubiquitinated proteins, or phosphorylated/pan protein levels of 4E-BP1, p70S6k, and AMPK. One week of AR after a high-volume training block instigates marginal molecular differences in skeletal muscle relative to PR. From a practical standpoint, however, both paradigms elicited largely similar responses.

An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men.

We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2 ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10-7 for rs4675569, 1.7 × 10-6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.