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We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post‐RE (+65% and +36%, P < 0.001); however, the last RE bout response was attenuated compared to the first bout (P = 0.045). Although cycling exercise did not alter MyHCTotal fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHCTotal fragmentation (∼108%, P < 0.001). Mechanistic C2C12 myotube experiments indicated that MyHCTotal fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease‐associated muscle atrophy affect these outcomes is needed. Highlights: What is the central question of this study?How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation.What is the main finding and its importance?This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We recently reported that vastus lateralis (VL) cross‐sectional area (CSA) increases after 7 weeks of resistance training (RT, 2 days/week), with declines occurring following 7 weeks of subsequent treadmill high‐intensity interval training (HIIT) (3 days/week). Herein, we examined the effects of this training paradigm on skeletal muscle proteolytic markers. VL biopsies were obtained from 11 untrained college‐aged males at baseline (PRE), after 7 weeks of RT (MID), and after 7 weeks of HIIT (POST). Tissues were analysed for proteolysis markers, and in vitro experiments were performed to provide additional insights. Atrogene mRNAs (TRIM63, FBXO32, FOXO3A) were upregulated at POST versus both PRE and MID (P < 0.05). 20S proteasome core protein abundance increased at POST versus PRE (P = 0.031) and MID (P = 0.049). 20S proteasome activity, and protein levels for calpain‐2 and Beclin‐1 increased at MID and POST versus PRE (P < 0.05). Ubiquitinated proteins showed model significance (P = 0.019) with non‐significant increases at MID and POST (P > 0.05). in vitro experiments recapitulated the training phenotype when stimulated with a hypertrophic stimulus (insulin‐like growth factor 1; IGF1) followed by a subsequent AMP‐activated protein kinase activator (5‐aminoimidazole‐4‐carboxamide ribonucleotide; AICAR), as demonstrated by larger myotube diameter in IGF1‐treated cells versus IGF1 followed by AICAR treatments (I+A; P = 0.017). Muscle protein synthesis (MPS) levels were also greater in IGF1‐treated versus I+A myotubes (P < 0.001). In summary, the loss in RT‐induced VL CSA with HIIT coincided with increases in several proteolytic markers, and sustained proteolysis may have driven this response. Moreover, while not measured in humans, we interpret our in vitro data to suggest that (unlike RT) HIIT does not stimulate MPS. New Findings: What is the central question of this study?Determining if HIIT‐induced reductions in muscle hypertrophy following a period of resistance training coincided with increases in proteolytic markers.What is the main finding and its importance?Several proteolytic markers were elevated during the HIIT training period implying that increases in muscle proteolysis may have played a role in HIIT‐induced reductions in muscle hypertrophy. [ABSTRACT FROM AUTHOR]

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. V̇O2max${\dot V_{{{\mathrm{O}}_2}\max }}$, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We investigated the effects of aging and long‐term physical activity on markers of mitochondrial function and dynamics in the cortex and cerebellum of female rats. Additionally, we interrogated markers of oxidative damage and antioxidants. Thirty‐four female Lewis rats were separated into three groups. A young group (YNG, n = 10) was euthanized at 6 months of age. Two other groups were aged to 15 months and included a physical activity group (MA‐PA, n = 12) and a sedentary group (MA‐SED, n = 12). There were no age effects for any of the variables investigated, except for SOD2 protein levels in the cortex (+6.5%, p = 0.012). Long‐term physical activity increased mitochondrial complex IV activity in the cortex compared to YNG (+85%, p = 0.016) and MA‐SED (+82%, p = 0.023) and decreased carbonyl levels in the cortex compared to YNG (−12.49%, p = 0.034). Our results suggest that the mitochondrial network and redox state of the brain of females may be more resilient to the aging process than initially thought. Further, voluntary wheel running had minimal beneficial effects on brain markers of oxidative damage and mitochondrial physiology. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

R5475 --> 886.13 --> Objective: To determine if markers of skeletal muscle extracellular matrix (ECM) content and ECM remodeling are indicators of hypertrophy in previously untrained collage aged males. Hypotheses: Higher‐responders (HR) to resistance training would demonstrate more malleable changes in assayed ECM markers than lower‐responders (LR). Methods: Untrained, college‐aged males (n=38, 21±3 years old) participated in 10 weeks of full‐body progressive resistance training (2x weekly) which included the leg press, bench press, leg extension, deadlift, and lat pulldown exercises. Participants completed a pre‐testing battery (DXA, ultrasound, pQCT and strength testing) and donated a vastus lateralis (VL) biopsy approximately one week prior to training. Participants completed post‐testing 72 hours following their last training bout, and this mimicked pre‐testing. Participants were then sorted into HR (n=10) and LR (n=10) based on changes in lean body mass, mid‐thigh cross‐sectional area (CSA), VL thickness, and deadlift strength changes. Muscle tissue from these 20 participants were processed for western blotting targeting MMP‐2, MMP‐9, MMP‐14, TIMP‐1, TIMP‐2, collagen‐1, and collagen‐4 protein levels. Global MMP activity was also performed on whole tissue lysates, and fascial thickness was measured from ultrasound images. All dependent variables were analyzed in SPSS (v22.0) using two‐way (group*time) repeated measures ANOVAs. Results: No significant group*time interactions or main effects of time were detected for MMP‐2, MMP‐9, TIMP‐1, TIMP‐2, Collagen‐1, or Collagen‐4 protein levels (p > 0.05). MMP activity and VL fascial thickness also revealed no significant group*time interactions or main effects of time (p > 0.05). A significant main effect of time (p = 0.009) and group*time interaction (p = 0.007) was detected for MMP‐14. Further analysis revealed a significant difference between HR and LR prior to training (p = 0.026) along with a significant decrease from pre to post in HR (p = 0.002) Conclusions: Our data suggest that skeletal muscle ECM markers did not differentiate higher‐responders versus lower‐responders to resistance training. However, MMP‐14 was responsive to resistance training and significantly different between response clusters prior to resistance training, and this warrants further investigation. [ABSTRACT FROM AUTHOR]