Changes in muscle cross-sectional area during two menstrual cycles may not be exclusively attributed to resistance training.

This study investigated the impact of menstrual cycle (MC) phases and resistance training (RT) on muscle cross-sectional area (CSA) in two MCs utilizing a within-subject design. Twenty women with regular MCs had their legs randomly allocated to either the control (CON) or RT condition, which included 16 training sessions over two MCs. CSA, estradiol (E2), and progesterone (P4) were assessed during the menstruation (M), ovulation (O), and luteal (L) phases in the first (M1, O1, L1) and second (M2, O2, L2) MCs and at the beginning of the third MC (M3). P4 values were significantly higher during the luteal phase than during menstruation (P < 0.0001) and ovulation (P < 0.0001). No significant differences in E2 concentrations were observed between the MC phases (P = 0.08). For the RT condition, the CSA showed significant increases at O2, L2, and M3 compared to baseline (M1) (all P < 0.0001). No significant changes were observed for the CON condition during the two MCs (P > 0.05). However, RT condition showed a significant change in average CSA across two MCs. Additionally, individual analyses revealed that 19 participants showed variation in CSA above or below the minimum detectable difference during the two MCs. These findings suggest that changes in muscle CSA observed during two MCs may not be exclusively attributed to RT.

Androgen receptor markers do not differ between nonresponders and responders to resistance training-induced muscle hypertrophy.

The aim of this study was to investigate whether baseline values and acute and chronic changes in androgen receptors (AR) markers, including total AR, cytoplasmic (cAR), and nuclear (nAR) fractions, as well as DNA-binding activity (AR-DNA), are involved in muscle hypertrophy responsiveness by comparing young nonresponder and responder individuals. After 10 wk of resistance training (RT), participants were identified as nonresponders using two typical errors (TE) obtained through two muscle cross-sectional area (mCSA) ultrasound measurements (2 × TE; 4.94%), and the highest responders within our sample were numerically matched. Muscle biopsies were performed at baseline, 24 h after the first RT session (acute responses), and 96 h after the last session (chronic responses). AR, cAR, and nAR were analyzed using Western blotting, and AR-DNA was analyzed using an ELISA-oligonucleotide assay. Twelve participants were identified as nonresponders (ΔmCSA: -1.32%) and 12 as responders (ΔmCSA: 21.35%). There were no baseline differences between groups in mCSA, AR, cAR, nAR, or AR-DNA (P > 0.05). For acute responses, there was a significant difference between nonresponders (+19.5%) and responders (-14.4%) in AR-DNA [effect size (ES) = -1.39; 95% confidence interval (CI): -2.53 to -0.16; P = 0.015]. There were no acute between-group differences in any other AR markers (P > 0.05). No significant differences between groups were observed in chronic responses across any AR markers (P > 0.05). Nonresponders and responders presented similar baseline, acute, and chronic results for the majority of the AR markers. Thus, our findings do not support the influence of AR markers on muscle hypertrophy responsiveness to RT in untrained individuals.NEW & NOTEWORTHY We explored, for the first time, the influence of androgen receptor (AR) through the separation of cytoplasmic and nuclear cell fractions [i.e., cytoplasmic androgen receptor (cAR), nuclear androgen receptor (nAR), and androgen receptor DNA-binding activity (AR-DNA)] on muscle hypertrophy responsiveness to resistance training. The absence of muscle hypertrophy in naïve individuals does not seem to be explained by baseline values, and acute or chronic changes in AR markers.

Skeletal muscle myosin heavy chain fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.

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.

Exercise training effect on skeletal muscle motor drive in older adults: A systematic review with meta-analysis of randomized controlled trials.

The meta-analysis aimed to determine whether exercise training can positively change indices of motor drive, i.e., the input from the central nervous system to the muscle, and how training characteristics, motor drive assessment, assessed muscle, and testing specificity could modulate the changes in motor drive in older adults. A random-effect meta-analysis model using standardized mean differences (Hedges' g) determined treatment effects. Moderators (e.g., training type and intensity) and meta-regressors (e.g., number of sessions) were performed using mixed- and fixed-effect models. A significant Q-test, followed by pairwise post hoc comparisons, determined differences between levels of the categorical moderators. Methodological quality was assessed using the Cochrane risk of bias tool. Ten randomized controlled trials, 290 older adults, met the inclusion criteria. Only strength and power exercise training were retrieved from the search and included in the analysis. Strength (g = 0.60, 95 % CI 0.24 to 0.96) and power training (g = 0.51, 95 % CI 0.02 to 1.00) increased motor drive compared with a control condition. High (g = 0.66; 95 % CI 0.34 to 0.97) and low-high (g = 1.23; 95 % CI 0.19 to 2.27) combinations of training intensities increased motor drive compared to the control condition. The multi-joint training and testing exercise structure (g = 1.23; 95 % CI 0.79 to 1.67) was more effective in increasing motor drive (Qdf=2 = 14.15; p = 0.001) than the multi-single joint structure (g = 0.46; 95 % CI 0.06 to 0.85). Therefore, strength and power training with high volume and intensity associated with multi-joint training and testing combination of exercises seem to improve skeletal muscle motor drive in older adults effectively.

Skeletal muscle myosin heavy chain protein fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.

We sought to examine how resistance exercise (RE), cycling exercise, and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation in humans. In the first study (1boutRE), younger adult men (n=8; 5±2 years of RE experience) performed a lower body RE bout with vastus lateralis (VL) biopsies obtained immediately before, 3-, and 6-hours post-exercise. In the second study (10weekRT), VL biopsies were obtained in untrained younger adults (n=36, 18 men and 18 women) before and 24 hours (24h) after their first/naïve RE bout. These participants also engaged in 10 weeks (24 sessions) of resistance training and donated VL biopsies before and 24h after their last RE bout. VL biopsies were also examined from a third acute cycling study (n=7) and a fourth study involving two weeks of leg immobilization (n=20, 15 men and 5 women) to determine how MyHC fragmentation was affected. In the 1boutRE study, the fragmentation of all MyHC isoforms (MyHCTotal) increased 3 hours post-RE (~ +200%, p=0.018) and returned to pre-exercise levels by 6 hours post-RE. Immunoprecipitation of MyHCTotal revealed ubiquitination levels remained unaffected at the 3- and 6-hour post-RE time points. Interestingly, a greater increase in magnitude for MyHC type IIa versus I isoform fragmentation occurred 3-hours post-RE (8.6±6.3-fold versus 2.1±0.7-fold, p=0.018). In all 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24h post-RE (+65% and +36%, respectively; p<0.001); however, the last RE bout response was attenuated compared to the first bout (p=0.045). The first/naïve bout response was significantly elevated in females only (p<0.001), albeit females also demonstrated a last bout attenuation response (p=0.002). Although an acute cycling bout did not alter MyHCTotal fragmentation, ~8% VL atrophy with two weeks of leg immobilization led to robust MyHCTotal fragmentation (+108%, p<0.001), and no sex-based differences were observed. In summary, RE and disuse atrophy increase MyHC protein fragmentation. A dampened response with 10 weeks of resistance training, and more refined responses in well-trained men, suggest this is an adaptive process. Given the null polyubiquitination IP findings, more research is needed to determine how MyHC fragments are processed. Moreover, further research is needed to determine how aging and disease-associated muscle atrophy affect these outcomes, and whether MyHC fragmentation is a viable surrogate for muscle protein turnover rates.

Acute and Chronic Changes in Muscle Androgen Receptor Markers Are Not Associated with Muscle Hypertrophy in Women and Men.

PURPOSE: Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations between acute and chronic changes in skeletal muscle total AR, cytoplasmic AR (cAR), nuclear AR (nAR) and AR DNA-binding (AR-DNA) induced by resistance training (RT) and hypertrophy outcomes in women and men. This study aimed to investigate the acute and chronic effects of RT on skeletal muscle total AR, cAR, nAR contents and AR-DNA in women and men. Additionally, we investigated whether these acute and chronic changes in these markers were associated with muscle hypertrophy in both sexes. METHODS: Nineteen women and 19 men underwent 10 weeks of RT. Muscle biopsies were performed at baseline, 24 h after the first RT session and 96-120 h after the last session. AR, cAR and nAR were analyzed using Western blotting, and AR-DNA using an ELISA-oligonucleotide assay. Fiber cross-sectional area (fCSA) was analyzed through immunohistochemistry and muscle cross-sectional area (mCSA) by ultrasound. RESULTS: At baseline, men demonstrated greater nAR than women. Baseline cAR was significantly associated with type II fCSA hypertrophy in men. Acutely, both sexes decreased AR and cAR, whereas men demonstrated greater decreases in nAR. After 10 weeks of RT, AR and nAR remained unchanged, men demonstrated greater cAR compared to women, and both sexes decreased AR-DNA activity. Acute and chronic changes in AR markers did not correlate with muscle hypertrophy (type I/II fCSA and mCSA) in women or men. CONCLUSIONS: Baseline cAR content may influence hypertrophy in men, while neither RT-induced acute nor chronic changes in AR, cAR, nAR, and AR-DNA are associated with muscle hypertrophy in women or men.

Resistance training-induced changes in muscle proteolysis and extracellular matrix remodeling biomarkers in the untrained and trained states.

PURPOSE: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state. METHODS: Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period. RESULTS: There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged. CONCLUSION: Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.

Application of Artificial Intelligence to Automate the Reconstruction of Muscle Cross-Sectional Area Obtained by Ultrasound.

PURPOSE: Manual reconstruction (MR) of the vastus lateralis (VL) muscle cross-sectional area (CSA) from sequential ultrasound (US) images is accessible, is reproducible, and has concurrent validity with magnetic resonance imaging. However, this technique requires numerous controls and procedures during image acquisition and reconstruction, making it laborious and time-consuming. The aim of this study was to determine the concurrent validity of VL CSA assessments between MR and computer vision-based automated reconstruction (AR) of CSA from sequential images of the VL obtained by US. METHODS: The images from each sequence were manually rotated to align the fascia between images and thus visualize the VL CSA. For the AR, an artificial neural network model was utilized to segment areas of interest in the image, such as skin, fascia, deep aponeurosis, and femur. This segmentation was crucial to impose necessary constraints for the main assembly phase. At this stage, an image registration application, combined with differential evolution, was employed to achieve appropriate adjustments between the images. Next, the VL CSA obtained from the MR ( n = 488) and AR ( n = 488) techniques was used to determine their concurrent validity. RESULTS: Our findings demonstrated a low coefficient of variation (CV) (1.51%) for AR compared with MR. The Bland-Altman plot showed low bias and close limits of agreement (+1.18 cm 2 , -1.19 cm 2 ), containing more than 95% of the data points. CONCLUSIONS: The AR technique is valid compared with MR when measuring VL CSA in a heterogeneous sample.

Carbohydrate mouth rinse failed to reduce central fatigue, lower perceived exertion, and improve performance during incremental exercise.

We examined if carbohydrate (CHO) mouth rinse may reduce central fatigue and perceived exertion, thus improving maximal incremental test (MIT) performance. Nine recreational cyclists warmed up for 6 min before rinsing a carbohydrate (CHO) or placebo (PLA) solution in their mouth for 10 s in a double-blind, counterbalanced manner. Thereafter, they performed the MIT (25 W·min-1 increases until exhaustion) while cardiopulmonary and ratings of perceived exertion (RPE) responses were obtained. Pre- to post-MIT alterations in voluntary activation (VA) and peak twitch torque (Tw) were determined. Time-to-exhaustion (p = 0.24), peak power output (PPO; p = 0.45), and V̇O2MAX (p = 0.60) were comparable between conditions. Neither treatment main effect nor time-treatment interaction effect were observed in the first and second ventilatory threshold when expressed as absolute or relative V̇O2 (p = 0.78 and p = 0.96, respectively) and power output (p = 0.28 and p = 0.45, respectively) values, although with moderate-to-large effect sizes. RPE increased similarly throughout the tests and was comparable at the ventilatory thresholds (p = 0.56). Despite the time main effect revealing an MIT-induced central and peripheral fatigue as indicated by the reduced VA and Tw, CHO mouth rinse was ineffective in attenuating both fatigues. Hence, rinsing the mouth with CHO was ineffective in reducing central fatigue, lowering RPE, and improving MIT performance expressed as PPO and time-to-exhaustion. However, moderate-to-large effect sizes in power output values at VT1 and VT2 may suggest some beneficial CHO mouth rinse effects on these MIT outcomes.

Effects of low-load resistance training with blood flow restriction on muscle fiber myofibrillar and extracellular area.

Blood flow restriction applied during low-load resistance training (LL-BFR) induces a similar increase in the cross-sectional area of muscle fibers (fCSA) compared to traditional high-load resistance training (HL-RT). However, it is unclear whether LL-BFR leads to differential changes in myofibrillar spacing in muscle fibers and/or extracellular area compared to HL-RT. Therefore, this study aimed to investigate whether the hypertrophy of type I and II fibers induced by LL-BFR or HL-RT is accompanied by differential changes in myofibrillar and non-myofibrillar areas. In addition, we examined if extracellular spacing was differentially affected between these two training protocols. Twenty recreationally active participants were assigned to LL-BFR or HL-RT groups and underwent a 6-week training program. Muscle biopsies were taken before and after the training period. The fCSA of type I and II fibers, the area occupied by myofibrillar and non-myofibrillar components, and extracellular spacing were analyzed using immunohistochemistry techniques. Despite the significant increase in type II and mean (type I + II) fCSA (p < 0.05), there were no significant changes in the proportionality of the myofibrillar and non-myofibrillar areas [∼86% and ∼14%, respectively (p > 0.05)], indicating that initial adaptations to LL-BFR are primarily characterized by conventional hypertrophy rather than disproportionate non-myofibrillar expansion. Additionally, extracellular spacing was not significantly altered between protocols. In summary, our study reveals that LL-BFR, like HL-RT, induces skeletal muscle hypertrophy with proportional changes in the areas occupied by myofibrillar, non-myofibrillar, and extracellular components.

Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Effects of Resistance Training Overload Progression Protocols on Strength and Muscle Mass.

The aim of this study was to compare the effects of progressive overload in resistance training on muscle strength and cross-sectional area (CSA) by specifically comparing the impact of increasing load (LOADprog) versus an increase in repetitions (REPSprog). We used a within-subject experimental design in which 39 previously untrained young persons (20 men and 19 women) had their legs randomized to LOADprog and REPSprog. Outcomes were assessed before and after 10 weeks of training. Muscle strength was assessed using the one repetition maximum (1RM) test on the leg extension exercise, and the CSA of the vastus lateralis was assessed by ultrasonography. Both protocols increased 1RM values from pre (LOADprog: 52.90±16.32 kg; REPSprog: 51.67±15.84 kg) to post (LOADprog: 69.05±18.55 kg, REPSprog: 66.82±17.95 kg), with no difference between them (P+>+0.05). Similarly, both protocols also increased in CSA values from pre (LOADprog: 21.34±4.71 cm²; REPSprog: 21.08±4.62 cm²) to post (LOADprog: 23.53±5.41 cm², REPSprog: 23.39±5.19 cm²), with no difference between them (P+>+0.05). In conclusion, our findings indicate that the progression of overload through load or repetitions can be used to promote gains in strength and muscle hypertrophy in young men and women in the early stages of training.

Clinical and neuroimaging correlates in a pilot randomized trial of aerobic exercise for major depression.

BACKGROUND: Aerobic exercise (AE) combined with pharmacotherapy is known to reduce depressive symptoms; however, studies have not focused on long-term AE for volumetric changes of brain regions (amygdala, thalamus, and nucleus accumbens [NAcc]) linked to the control of affective responses and hopelessness in individuals with major depression (MD). In addition, AE with motor complexity (AEMC) would be more effective than AE in causing brain plasticity. We compared the effects of 24 weeks of AE and AEMC combined with pharmacotherapy on clinical and volumetric outcomes in individuals with MD. METHODS: Forty medicated individuals with MD were randomly assigned to nonexercising control (C), AE, and AEMC groups. The training groups exercised for 60 min, twice a week for 24 weeks. Clinical and volumetric outcomes were assessed before and after the 24 weeks. Effect size (ES) and confidence interval (CI) were calculated for within-group and between-groups changes. RESULTS: AE and AEMC reduced hopelessness (ES = -0.73 and ES = -0.62, respectively) and increased affective responses (ES = 1.24 and ES = 1.56, respectively). Only AE increased amygdala (ES = 0.27 left and ES = 0.34 right), thalamus (ES = 0.33 left and ES = 0.26 right) and left NAcc (ES = 0.54) volumes. AE was more effective than the C group in reducing hopelessness and causing brain plasticity. The changes in the right amygdala volume showed a strong trend in explaining 72 % of the changes in affective responses following AE (p = 0.06). LIMITATION: Lack of posttraining follow-up and small sample size. CONCLUSION: These preliminary data indicate that AE combined with pharmacotherapy can cause clinical improvement and brain plasticity in individuals with MD.

Time Course of Proteolysis Biomarker Responses to Resistance, High-Intensity Interval, and Concurrent Exercise Bouts.

ABSTRACT: Godwin, JS, Telles, GD, Vechin, FC, Conceição, MS, Ugrinowitsch, C, Roberts, MD, and Libardi, CA. Time course of proteolysis biomarker responses to resistance, high-intensity interval, and concurrent exercise bouts. J Strength Cond Res 37(12): 2326-2332, 2023-Concurrent exercise (CE) combines resistance exercise (RE) and high-intensity interval exercise (HIIE) in the same training routine, eliciting hypertrophy, strength, and cardiovascular benefits over time. Some studies suggest that CE training may hamper muscle hypertrophy and strength adaptations compared with RE training alone. However, the underlying mechanisms related to protein breakdown are not well understood. The purpose of this study was to examine how a bout of RE, HIIE, or CE affected ubiquitin-proteasome and calpain activity and the expression of a few associated genes, markers of skeletal muscle proteolysis. Nine untrained male subjects completed 1 bout of RE (4 sets of 8-12 reps), HIIE (12 × 1 minute sprints at V̇ o2 peak minimum velocity), and CE (RE followed by HIIE), in a crossover design, separated by 1-week washout periods. Muscle biopsies were obtained from the vastus lateralis before (Pre), immediately post, 4 hours (4 hours), and 8 hours (8 hours) after exercise. FBXO32 mRNA expression increased immediately after exercise (main time effect; p < 0.05), and RE and CE presented significant overall values compared with HIIE ( p < 0.05). There was a marginal time effect for calpain-2 mRNA expression ( p < 0.05), with no differences between time points ( p > 0.05). No significant changes occurred in TRIM63/MuRF-1 and FOXO3 mRNA expression, or 20S proteasome or calpain activities ( p > 0.05). In conclusion, our findings suggest that 1 bout of CE does not promote greater changes in markers of skeletal muscle proteolysis compared with 1 bout of RE or HIIE.

Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.

Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.

Acute changes in serum and skeletal muscle steroids in resistance-trained men.

Introduction: Resistance exercise can significantly increase serum steroid concentrations after an exercise bout. Steroid hormones are involved in the regulation of several important bodily functions (e.g., muscle growth) through both systemic delivery and local production. Thus, we aimed to determine whether resistance exercise-induced increases in serum steroid hormone concentrations are accompanied by enhanced skeletal muscle steroid concentrations, or whether muscle contractions per se induced by resistance exercise can increase intramuscular steroid concentrations. Methods: A counterbalanced, within-subject, crossover design was applied. Six resistance-trained men (26 ± 5 years; 79 ± 8 kg; 179 ± 10 cm) performed a single-arm lateral raise exercise (10 sets of 8 to 12 RM - 3 min rest between sets) targeting the deltoid muscle followed by either squat exercise (10 sets of 8 to 12 RM - 1 min rest) to induce a hormonal response (high hormone [HH] condition) or rest (low hormone [LH] condition). Blood samples were obtained pre-exercise and 15 min and 30 min post-exercise; muscle specimens were harvested pre-exercise and 45 min post-exercise. Immunoassays were used to measure serum and muscle steroids (total and free testosterone, dehydroepiandrosterone sulfate, dihydrotestosterone, and cortisol; free testosterone measured only in serum and dehydroepiandrosterone only in muscle) at these time points. Results: In the serum, only cortisol significantly increased after the HH protocol. There were no significant changes in muscle steroid concentrations after the protocols. Discussion: Our study provides evidence that serum steroid concentration increases (cortisol only) seem not to be aligned with muscle steroid concentrations. The lack of change in muscle steroid after protocols suggests that resistance-trained individuals were desensitized to the exercise stimuli. It is also possible that the single postexercise timepoint investigated in this study might be too early or too late to observe changes. Thus, additional timepoints should be examined to determine if RE can indeed change muscle steroid concentrations either by skeletal muscle uptake of these hormones or the intramuscular steroidogenesis process.

Interrelated but Not Time-Aligned Response in Myogenic Regulatory Factors Demethylation and mRNA Expression after Divergent Exercise Bouts.

INTRODUCTION: DNA methylation regulates exercise-induced changes in the skeletal muscle transcriptome. However, the specificity and the time course responses in the myogenic regulatory factors DNA methylation and mRNA expression after divergent exercise modes are unknown. PURPOSE: This study aimed to compare the time course changes in DNA methylation and mRNA expression for selected myogenic regulatory factors ( MYOD1 , MYF5 , and MYF6 ) immediately after, 4 h after, and 8 h after a single bout of resistance exercise (RE), high-intensity interval exercise (HIIE), and concurrent exercise (CE). METHODS: Nine healthy but untrained males (age, 23.9 ± 2.8 yr; body mass, 70.1 ± 14.9 kg; peak oxygen uptake [V̇O 2peak ], 41.4 ± 5.2 mL·kg -1 ·min -1 ; mean ± SD) performed a counterbalanced, randomized order of RE (4 × 8-12 repetition maximum), HIIE (12 × 1 min sprints at V̇O 2peak running velocity), and CE (RE followed by HIIE). Skeletal muscle biopsies (vastus lateralis) were taken before (REST) immediately (0 h), 4 h, and 8 h after each exercise bout. RESULTS: Compared with REST, MYOD1 , MYF5 , and MYF6 , mean methylation across all CpGs analyzed was reduced after 4 and 8 h in response to all exercise protocols ( P < 0.05). Reduced levels of MYOD1 methylation were observed after HIIE and CE compared with RE ( P < 0.05). Compared with REST, all exercise bouts increased mRNA expression over time ( MYOD1 at 4 and 8 h, and MYF6 at 4 h; P < 0.05). MYF5 mRNA expression was lower after 4 h compared with 0 h and higher at 8 h compared with 4 h ( P < 0.05). CONCLUSIONS: We observed an interrelated but not time-aligned response between the exercise-induced changes in myogenic regulatory factors demethylation and mRNA expression after divergent exercise modes. Despite divergent contractile stimuli, changes in DNA methylation and mRNA expression in skeletal muscle were largely confined to the late (4-8 h) recovery period and similar between the different exercise challenges.

Objective Physical Activity Accumulation and Brain Volume in Older Adults: An MRI and Whole-Brain Volume Study.

A decrease in brain volume (ie, brain atrophy) is a marker of cognitive health in older adults. Insufficient weekly accumulation of moderate and vigorous physical activity (MVPA) has been associated with lower brain volume. As this association has been established for a small number of brain areas and structures and atrophy rates seem to be nonuniform between them, more comprehensive analyses are warranted. We compared the volume of 71 brain areas and structures in 45 older adults who met and did not meet objectively measured MVPA recommendations. In addition, we used multiple regression models to determine whether cardiorespiratory fitness (VO2PEAK), MVPA, and health-related risk factors could affect the atrophy of brain areas and structures. An accelerometer (GT9-X ActiGraph) was worn for 7 days. Participants were then classified into 2 groups: <150 minutes MVPA (<150'MVPA; n = 20) and ≥150 minutes MVPA (≥150'MVPA; n = 25) per week. Older adults who accumulated ≥150'MVPA per week had significantly higher absolute and relative (% of intracranial volume) volumes of 39 and 9 brain areas and structures, respectively, than those who accumulated <150'MVPA per week. Higher VO2PEAK seems to be a key predictor of the atrophy of brain areas and structures. In conclusion, meeting weekly physical activity recommendations seems to have a widespread effect on preserving the volume of more than 30 brain areas and structures in older adults. VO2PEAK seems to be the most frequent and important predictor of brain volume preservation.

Increased sympathetic nervous system impairs prognosis in lung cancer patients: a scoping review of clinical studies.

Aim: To summarize current knowledge, gaps, quality of the evidence and show main results related to the role of the autonomic nervous system in lung cancer. Methods: Studies were identified through electronic databases (PubMed, Scopus, Embase and Cochrane Library) in October 2023, and a descriptive analysis was performed. Twenty-four studies were included, and most were observational. Results: Our data indicated an increased expression of ß-2-adrenergic receptors in lung cancer, which was associated with poor prognosis. However, the use of ß-blockers as an add-on to standard treatment promoted enhanced overall survival, recurrence-free survival and reduced metastasis occurrence. Conclusion: Although the results herein seem promising, future research using high-quality prospective clinical trials is required to draw directions to guide clinical interventions.

Lung cancer is one of the most common causes of cancer-related deaths in the world, which often goes undiagnosed until it is in an advanced stage. Recently, the autonomic nervous system (sympathetic and parasympathetic nervous systems) has been identified as a regulator of cancer growth and spread, including lung cancer. In fact, preclinical studies have demonstrated that autonomic innervation in lung cancer can trigger tumor progression, metastasis, and resistance to treatment, worsening the prognosis. In this sense, add-on strategies to standard cancer treatments have been investigating and one of them has stood out: the incidental use of ß-blockers (patients who used ß-blockers for the treatment of hypertension and/or cardiovascular diseases or anxiety) before surgeries or during chemotherapy, which has been associated with improved clinical outcomes. Thus, a scoping review was conducted to summarizing the current knowledge about the quality of evidence, gaps and main results related to the role of the autonomic nervous system in human lung cancer. Data from this review indicated an increase in sympathetic nervous system receptors associated with a worse prognosis in patients with lung cancer. Indeed, those patients who took ß-blockers along with lung cancer treatment showed an increase in survival and a reduction in the occurrence of metastases. Although the results herein seem promising, further prospective clinical studies are needed to investigate the effect of the intentional and controlled use of ß-blockers as an add-on strategy on the treatment of different types and stages of lung cancer.