Dynamic transcriptomic responses to divergent acute exercise stimuli in young adults.

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n = 21, 12 M/9 F, 22 ± 3 yr) or HITT (n = 19, 11 M/8 F, 22 ± 2 yr). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR ≤ 0.05) immediately (h0, EVs only), h3, and h24 postexercise within and between exercise protocols. In aaddition, all apparently responsive transcripts (FDR < 0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and interregulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but less intense stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.NEW & NOTEWORTHY We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.

Muscle transcriptomic circuits linked to periarticular physiology in end-stage osteoarthritis.

The ability of individuals with end-stage osteoarthritis (OA) to functionally recover from total joint arthroplasty is highly inconsistent. The molecular mechanisms driving this heterogeneity have yet to be elucidated. Furthermore, OA disproportionately impacts females, suggesting a need for identifying female-specific therapeutic targets. We profiled the skeletal muscle transcriptome in females with end-stage OA (n = 20) undergoing total knee or hip arthroplasty using RNA-Seq. Single-gene differential expression (DE) analyses tested for DE genes between skeletal muscle overlaying the surgical (SX) joint and muscle from the contralateral (CTRL) leg. Network analyses were performed using Pathway-Level Information ExtractoR (PLIER) to summarize genes into latent variables (LVs), i.e., gene circuits, and link them to biological pathways. LV differences in SX versus CTRL muscle and across sources of muscle tissue (vastus medialis, vastus lateralis, or tensor fascia latae) were determined with ANOVA. Linear models tested for associations between LVs and muscle phenotype on the SX side (inflammation, function, and integrity). DE analysis revealed 360 DE genes (|Log2 fold-difference| ≥ 1, FDR ≤ 0.05) between the SX and CTRL limbs, many associated with inflammation and lipid metabolism. PLIER analyses revealed circuits associated with protein degradation and fibro-adipogenic cell gene expression. Muscle inflammation and function were linked to an LV associated with endothelial cell gene expression highlighting a potential regulatory role of endothelial cells within skeletal muscle. These findings may provide insight into potential therapeutic targets to improve OA rehabilitation before and/or following total joint replacement.

Resistance training variable manipulations are less relevant than intrinsic biology in affecting muscle fiber hypertrophy.

We aimed to investigate whether muscle fiber cross-sectional area (fCSA) and associated molecular processes could be differently affected at the group and individual level by manipulating resistance training (RT) variables. Twenty resistance-trained subjects had each leg randomly allocated to either a standard RT (RT-CON: without specific variables manipulations) or a variable RT (RT-VAR: manipulation of load, volume, muscle action, and rest interval at each RT session). Muscle fCSA, satellite cell (SC) pool, myonuclei content, and gene expression were assessed before and after training (chronic effect). Gene expression was assessed 24 h after the last training session (acute effect). RT-CON and RT-VAR increased fCSA and myonuclei domain in type I and II fibers after training (p < 0.05). SC and myonuclei content did not change for both conditions (p > 0.05). Pax-7, MyoD, MMP-2 and COL3A1 (chronic) and MGF, Pax-7, and MMP-9 (acute) increased similar for RT-CON and RT-VAR (p < 0.05). The increase in acute MyoG expression was significantly higher for the RT-VAR than RT-CON (p < 0.05). We found significant correlation between RT-CON and RT-VAR for the fCSA changes (r = 0.89). fCSA changes were also correlated to satellite cells (r = 0.42) and myonuclei (r = 0.50) changes. Heatmap analyses showed coupled changes in fCSA, SC, and myonuclei responses at the individual level, regardless of the RT protocol. The high between and low within-subject variability regardless of RT protocol suggests that the intrinsic biological factors seem to be more important to explain the magnitude of fCSA gains in resistance-trained subjects.

Session Rating of Perceived Exertion as an Efficient Tool for Individualized Resistance Training Progression.

ABSTRACT: Gomes, RL, Lixandrão, ME, Ugrinowitsch, C, Moreira, A, Tricoli, V, and Roschel, H. Session rating of perceived exertion as an efficient tool for individualized resistance training progression. J Strength Cond Res 36(4): 971-976, 2022-The present study aimed to investigate the effects of an individualized resistance training (RT) progression model based on the session rating of perceived exertion (RPE) on gains in muscle mass and strength when compared with a conventional predetermined progression method (PP). Twenty previously trained young male subjects were randomly allocated to 1 of the 2 groups: RPE (n = 10) or PP (n = 10). Muscle cross-sectional area (CSA) and maximum dynamic strength were assessed at baseline and after 6 weeks. The RPE-based progression model resulted in a lower number of high-intensity sessions compared with the PP-based model. Despite this, both groups showed significant and similar increases in CSA (p < 0.0001; RPE = 6.55 ± 5.27% and PP = 9.65 ± 3.63%) and strength (p < 0.0001; RPE = 9.68 ± 4.57% and PP = 9.28 ± 4.01%) after the intervention period. No significant between-group difference was observed for total training volume (RPE = 45,366.00 ± 10,190.00 kg and PP = 47,779.00 ± 5,685.00 kg; p = 0.52). Our results showed that an RT progression model based on session-to-session physiological response assessments resulted in fewer high-intensity training sessions while allowing for similar gains in muscle strength and mass. Thus, trainees are encouraged to adopt session RPE as a potential tool to control workload progression throughout a training period and allowing the optimization of training stimulus on an individual basis.

Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men.

ß-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day-1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day-1) improved isometric, but not isokinetic or isotonic endurance performance.

Individual Muscle Hypertrophy and Strength Responses to High vs. Low Resistance Training Frequencies.

Damas, F, Barcelos, C, Nóbrega, SR, Ugrinowitsch, C, Lixandrão, ME, Santos, LMEd, Conceição, MS, Vechin, FC, and Libardi, CA. Individual muscle hypertrophy and strength responses to high vs. low resistance training frequencies. J Strength Cond Res 33(4): 897-901, 2019-The aim of this short communication was to compare the individual muscle mass and strength gains with high (HF) vs. low (LF) resistance training (RT) frequencies using data from our previous study. We used a within-subject design in which 20 subjects had one leg randomly assigned to HF (5× per week) and the other to LF (2 or 3× per week). Muscle cross-sectional area and 1 repetition maximum were assessed at baseline and after 8 weeks of RT. HF showed a higher 8-week accumulated total training volume (TTV) (p < 0.0001) compared with LF. Muscle cross-sectional area and 1 repetition maximum values increased significantly and similarly for HF and LF protocols (p > 0.05). This short communication highlights that some individuals showed greater muscle mass and strength gains after HF (31.6 and 26.3% of individuals, respectively), other had greater gains with LF (36.8 and 15.8% of individuals, respectively), and even others showed similar responses between HF and LF, regardless of the consequent higher or lower TTV resulted from HF and LF, respectively. Importantly, individual manipulation of RT frequency can improve the intrasubject responsiveness to training, but the effect is limited to each individual's capacity to respond to RT. Finally, individual response to different frequencies and resulted TTV does not necessarily agree between muscle hypertrophy and strength gains.

Blood-Flow Restriction Resistance Exercise Promotes Lower Pain and Ratings of Perceived Exertion Compared With Either High- or Low-Intensity Resistance Exercise Performed to Muscular Failure.

CONTEXT: Given the comparable muscle hypertrophy constantly observed between blood-flow restriction exercise (BFR-RE) and conventional resistance exercise, understanding their particular rating of perceived exertion (RPE) and pain may help to better prescribe exercise at a low-discomfort level, thus increasing its feasibility. DESIGN: Randomized crossover study. OBJECTIVE: To compare the RPE and pain response between conventional high- (HI-RE) and low-intensity resistance exercise (LI-RE) protocols to failure with a nonmuscular failure LI-RE associated with BFR-RE. PARTICIPANTS: A total of 12 men (age: 20 [3] y; body mass: 73.5 [9] kg; height: 174 [6] cm). INTERVENTIONS: Four sets of 45° leg-press exercises in 3 different conditions: (1) BFR-RE (15 repetitions; 30% 1-repetition maximum), (2) HI-RE (80% 1-repetition maximum to muscular failure), and (3) LI-RE (30% 1-repetition maximum to muscular failure). MAIN OUTCOME MEASURES: RPE and pain were assessed immediately before exercise session and after the end of each of the 4 sets. RESULTS: RPE and pain levels increased throughout the exercise sets for all RE protocols (all, Ps < .05). HI-RE and LI-RE protocols showed similar increase in RPE and pain levels during all exercise sets (P < .05); however, both protocols demonstrated higher RPE and pain response compared with BFR-RE after each of the 4 sets (all Ps < .05 between-group comparisons). CONCLUSIONS: Our results demonstrated that both HI-RE and LI-RE to muscular failure resulted in similar and significant increases in RPE and pain levels, regardless of exercise intensity. In addition, nonmuscular failure BFR-RE also increased RPE and pain response, however, to a lower extent compared with either HI-RE or LI-RE.

Resistance training in young men induces muscle transcriptome-wide changes associated with muscle structure and metabolism refining the response to exercise-induced stress.

BACKGROUND: Gene expression is an important process underpinning the acute and chronic adaptive response to resistance exercise (RE) training. PURPOSE: To investigate the effect of training status on vastus lateralis muscle global transcriptome at rest and following acute RE. METHODS: Muscle biopsies of nine young men (age: 26(2) years; body mass: 69(9) kg; height 172(6) cm) who undertook RE training for 10 weeks were collected pre and 24 h post-RE in the untrained (W1) and trained (W10) states and analysed using microarray. Tests of differential expression were conducted for rested and after RE contrasts in both training states. To control for false discovery rate (FDR), multiple testing correction was performed at a cut-off of FDR < 0.05. RESULTS: Unaccustomed RE (at W1) upregulated muscle gene transcripts related to stress (e.g., heat shock proteins), damage and inflammation, structural remodelling, protein turnover and increased translational capacity. Trained muscles (at W10) showed changes in the transcriptome signature regarding the regulation of energy metabolism, favouring a more oxidative one, upregulated antioxidant- and immune-related genes/terms, and gene transcripts related to the cytoskeleton and extracellular matrix, muscle contraction, development and growth. CONCLUSIONS: These results highlight that chronic repetition of RE changes muscle transcriptome response towards a more refined response to RE-induced stress.

Effects of weightlifting exercise, traditional resistance and plyometric training on countermovement jump performance: a meta-analysis.

Jump performance is considered an important factor in many sports. Thus, strategies such as weightlifting (WL) exercises, traditional resistance training (TRT) and plyometric training (PT) are effective at improving jump performance. However, it is not entirely clear which of these strategies can enable greater improvements on jump height. Thus, the purpose of the meta-analysis was to compare the improvements on countermovement jump (CMJ) performance between training methods which focus on WL exercises, TRT, and PT. Seven studies were included, of which one study performed both comparison. Therefore, four studies comparing WL exercises vs. TRT (total n = 78) and four studies comparing WL exercises vs. PT (total n = 76). The results showed greater improvements on CMJ performance for WL exercises compared to TRT (ESdiff: 0.72 ± 0.23; 95%CI: 0.26, 1.19; P = 0.002; Δ % = 7.5 and 2.1, respectively). The comparison between WL exercises vs. PT revealed no significant difference between protocols (ESdiff: 0.15 ± 0.23; 95%CI: -0.30, 0.60; P = 0.518; Δ % = 8.8 and 8.1, respectively). In conclusion, WL exercises are superior to promote positive changes on CMJ performance compared to TRT; however, WL exercises and PT are equally effective at improving CMJ performance.

Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage.

KEY POINTS: Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes in myofibrillar protein synthesis (MyoPS) after an initial resistance exercise (RE) bout in the first week of RT (T1) were greater than those seen post-RE at the third (T2) and tenth week (T3) of RT, with values being similar at T2 and T3. Muscle damage (Z-band streaming) was the highest during post-RE recovery at T1, lower at T2 and minimal at T3. When muscle damage was the highest, so was the integrated MyoPS (at T1), but neither were related to hypertrophy; however, integrated MyoPS at T2 and T3 were correlated with hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent increases in MyoPS mainly after a progressive attenuation of muscle damage. ABSTRACT: Skeletal muscle hypertrophy is one of the main outcomes of resistance training (RT), but how hypertrophy is modulated and the mechanisms regulating it are still unknown. To investigate how muscle hypertrophy is modulated through RT, we measured day-to-day integrated myofibrillar protein synthesis (MyoPS) using deuterium oxide and assessed muscle damage at the beginning (T1), at 3 weeks (T2) and at 10 weeks of RT (T3). Ten young men (27 (1) years, mean (SEM)) had muscle biopsies (vastus lateralis) taken to measure integrated MyoPS and muscle damage (Z-band streaming and indirect parameters) before, and 24 h and 48 h post resistance exercise (post-RE) at T1, T2 and T3. Fibre cross-sectional area (fCSA) was evaluated using biopsies at T1, T2 and T3. Increases in fCSA were observed only at T3 (P = 0.017). Changes in MyoPS post-RE at T1, T2 and T3 were greater at T1 (P < 0.03) than at T2 and T3 (similar values between T2 and T3). Muscle damage was the highest during post-RE recovery at T1, attenuated at T2 and further attenuated at T3. The change in MyoPS post-RE at both T2 and T3, but not at T1, was strongly correlated (r ≈ 0.9, P < 0.04) with muscle hypertrophy. Initial MyoPS response post-RE in an RT programme is not directed to support muscle hypertrophy, coinciding with the greatest muscle damage. However, integrated MyoPS is quickly 'refined' by 3 weeks of RT, and is related to muscle hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent changes in MyoPS post-RE in RT, which coincides with progressive attenuation of muscle damage.

Early resistance training-induced increases in muscle cross-sectional area are concomitant with edema-induced muscle swelling.

PURPOSE: It has been proposed that skeletal muscle shows signs of resistance training (RT)-induced muscle hypertrophy much earlier (i.e., ~3-4 weeks of RT) than previously thought. We determined if early increases in whole muscle cross-sectional area (CSA) during a period of RT were concomitant with edematous muscle swelling and thus not completely attributable to hypertrophy. METHODS: We analyzed vastus lateralis muscle ultrasound CSA images and their respective echo intensities (CSA-USecho) at the beginning (T1), in the 3rd week of RT (T2) and at the end (T3) of a 10-week RT period in ten untrained young men. Functional parameters [training volume (TV = load × reps × sets) and maximal voluntary contraction (MVC)] and muscle damage markers (myoglobin and interleukin-6) were also assessed. RESULT: Muscle CSA increased significantly at T2 (~2.7%) and T3 (~10.4%) versus T1. Similarly, CSA-USecho increased at T2 (~17.2%) and T3 (~13.7%). However, when CSA-USecho was normalized to the increase in muscle CSA, only T2 showed a significantly higher USecho versus T1. Additionally, TV increased at T2 and T3 versus T1, but MVC increased only at T3. Myoglobin and Interleukin-6 were elevated at T2 versus T1, and myoglobin was also higher at T2 versus T3. CONCLUSION: We propose that early RT-induced increases in muscle CSA in untrained young individuals are not purely hypertrophy, since there is concomitant edema-induced muscle swelling, probably due to muscle damage, which may account for a large proportion of the increase. Therefore, muscle CSA increases (particularly early in an RT program) should not be labeled as hypertrophy without some concomitant measure of muscle edema/damage.

Time Course of Resistance Training-Induced Muscle Hypertrophy in the Elderly.

Extended periods of resistance training (RT) induce muscle hypertrophy. Nevertheless, to date, no study has investigated the time window necessary to observe significant changes in muscle cross-sectional area (CSA) in older adults. Therefore, this study investigated the time course of muscle hypertrophy after 10 weeks (20 sessions) of RT in the elderly. Fourteen healthy older subjects were randomly allocated in either the RT (n: 6) or control group (n: 8). The RT was composed of 4 sets × 10 repetitions (70-80% 1 repetition maximum [1RM]) in a leg press machine. The time course of vastus lateralis muscle hypertrophy (CSA) was assessed on a weekly basis by mode-B ultrasonography. Leg press muscle strength was assessed by dynamic 1RM test. Our results demonstrated that the RT group increased leg press 1RM by 42% (p ≤ 0.05) after 10 weeks of training. Significant increases in vastus lateralis muscle CSA were observed only after 18 sessions of training (9 weeks; p ≤ 0.05; 7.1%). In conclusion, our training protocol promoted muscle mass accrual in older subjects, and this was only observable after 18 sessions of RT (9 weeks).

Effects of exercise intensity and occlusion pressure after 12 weeks of resistance training with blood-flow restriction.

PURPOSE: We compared the effects of different protocols of blood-flow restriction training (BFRT) with different occlusion pressures and/or exercise intensities on muscle mass and strength. We also compared BFRT protocols with conventional high-intensity resistance training (RT). METHODS: Twenty-six subjects had each leg allocated to two of five protocols. BFRT protocols were performed at either 20 or 40 % 1-RM with either 40 or 80 % occlusion pressure: BFRT20/40, BFRT20/80, BFRT40/40, and BFRT40/80. Conventional RT was performed at 80 % 1-RM (RT80) without blood-flow restriction. Maximum dynamic strength (1-RM) and quadriceps cross-sectional area (CSA) were assessed at baseline and after 12 weeks. RESULTS: Regarding muscle mass, increasing occlusion pressure was effective only at very low intensity (BFRT20/40 0.78 % vs. BFRT20/80 3.22 %). No additional increase was observed at higher intensities (BFRT40/40 4.45 % vs. BFRT40/80 5.30 %), with no difference between the latter protocols and RT80 (5.90 %). Exercise intensity played a role in CSA when comparing groups with similar occlusion pressure. Muscle strength was similarly increased among BFRT groups (~12.10 %) but to a lesser extent than RT80 (21.60 %). CONCLUSION: In conclusion, BFRT protocols benefit from higher occlusion pressure (80 %) when exercising at very low intensities. Conversely, occlusion pressure seems secondary to exercise intensity in more intense (40 % 1-RM) BFRT protocols. Finally, when considering muscle strength, BFRT protocols seem less effective than high-intensity RT.

Comparisons between low-intensity resistance training with blood flow restriction and high-intensity resistance training on quadriceps muscle mass and strength in elderly.

High-intensity resistance training (HRT) has been recommended to offset age-related loss in muscle strength and mass. However, part of the elderly population is often unable to exercise at high intensities. Alternatively, low-intensity resistance training with blood flow restriction (LRT-BFR) has emerged. The purpose of this study was to compare the effects of LRT-BFR and HRT on quadriceps muscle strength and mass in elderly. Twenty-three elderly individuals, 14 men and 9 women (age, 64.04 ± 3.81 years; weight, 72.55 ± 16.52 kg; height, 163 ± 11 cm), undertook 12 weeks of training. Subjects were ranked according to their pretraining quadriceps cross-sectional area (CSA) values and then randomly allocated into one of the following groups: (a) control group, (b) HRT: 4 × 10 repetitions, 70-80% one repetition maximum (1RM), and (c) LRT-BFR: 4 sets (1 × 30 and 3 × 15 repetitions), 20-30% 1RM. The occlusion pressure was set at 50% of maximum tibial arterial pressure and sustained during the whole training session. Leg press 1RM and quadriceps CSA were evaluated at before and after training. A mixed-model analysis was performed, and the significance level was set at p ≤ 0.05. Both training regimes were effective in increasing pre- to post-training leg press 1RM (HRT: ∼54%, p < 0.001; LRT-BFR: ∼17%, p = 0.067) and quadriceps CSA (HRT: 7.9%, p < 0.001; LRT-BFR: 6.6%, p < 0.001); however, HRT seems to induce greater strength gains. In summary, LRT-BFR constitutes an important surrogate approach to HRT as an effective training method to induce gains in muscle strength and mass in elderly.

Vastus lateralis muscle cross-sectional area ultrasonography validity for image fitting in humans.

The present study aimed to determine the concurrent validity of ultrasound (US) measurement of the vastus lateralis muscle (VL) cross-sectional area (CSA) having magnetic resonance imaging (MRI) as the gold standard measurement, in a heterogeneous sample of participants. Thirty-one individuals (52.44 ± 16.37 years; 1.67 ± 0.11 m; 75.25 ± 13.82 kg) volunteered to participate in the study. All the images were performed in the right leg. Image-fitting technique (US) and computerized planimetry technique (US and MRI) were used to determine the VL CSA. The typical error (TE) of measurement was used to determine the concurrent validity of the US measurements. Our results demonstrated good validity of the US compared with the MRI measurements (TE = 0.37 cm; coefficient of variation = 1.75%). The Bland-Altman plot demonstrated bias of 0.07 ± 0.53 cm and limits of agreement of 0.96-1.11 cm. Based on our TE, bias and limits of agreement, we concluded that the US image-fitting technique is valid to assess the VL CSA in a heterogeneous sample of participants. Thereby, US can be used instead of MRI to assess changes in skeletal muscle morphology.

Higher resistance training volume offsets muscle hypertrophy nonresponsiveness in older individuals.

The magnitude of muscle hypertrophy in response to resistance training (RT) is highly variable between individuals (response heterogeneity). Manipulations in RT variables may modulate RT-related response heterogeneity; yet, this remains to be determined. Using a within-subject unilateral design, we aimed to investigate the effects of RT volume manipulation on whole muscle hypertrophy [quadriceps muscle cross-sectional area (qCSA)] among nonresponders and responders to a low RT dose (single-set). We also investigated the effects of RT volume manipulation on muscle strength in these responsiveness groups. Eighty-five older individuals [41M/44F, age = 68 ± 4 yr; body mass index (BMI) = 26.4 ± 3.7 kg/m2] had one leg randomly allocated to a single (1)-set and the contralateral leg allocated to four sets of unilateral knee-extension RT at 8-15 repetition maximum (RM) for 10-wk 2 days/wk. Pre- and postintervention, participants underwent magnetic resonance imaging (MRI) and unilateral knee-extension 1-RM strength testing. MRI typical error (2× TE = 3.27%) was used to classify individuals according to responsiveness patterns. n = 51 were classified as nonresponders (≤2× TE) and n = 34 as responders (>2× TE) based on pre- to postintervention change qCSA following the single-set RT protocol. Nonresponders to single-set training showed a dose response, with significant time × set interactions for qCSA and 1-RM strength, indicating greater gains in response to the higher volume prescription (time × set: P < 0.05 for both outcomes). Responders improved qCSA (time: P < 0.001), with a tendency toward higher benefit from the four sets RT protocol (time × set: P = 0.08); on the other hand, 1-RM increased similarly irrespectively of RT volume prescription (time × set: P > 0.05). Our findings support the use of higher RT volume to mitigate nonresponsiveness among older adults.NEW & NOTEWORTHY Using a within-subject unilateral design, we demonstrated that increasing resistance training (RT) volume may be a simple, effective strategy to improve muscle hypertrophy and strength gains among older adults who do not respond to low-volume RT. In addition, it could most likely be used to further improve hypertrophic outcomes in responders.

Adipocyte hypertrophy in mesenchymal stem cells from infants of mothers with obesity.

OBJECTIVE: Fat content of adipocytes derived from infant umbilical cord mesenchymal stem cells (MSCs) predicts adiposity in children through 4 to 6 years of age. This study tested the hypothesis that MSCs from infants born to mothers with obesity (Ob-MSCs) exhibit adipocyte hypertrophy and perturbations in genes regulating adipogenesis compared with MSCs from infants of mothers with normal weight (NW-MSCs). METHODS: Adipogenesis was induced in MSCs embedded in three-dimensional hydrogel structures, and cell size and number were measured by three-dimensional imaging. Proliferation and protein markers of proliferation and adipogenesis in undifferentiated and adipocyte differentiating cells were measured. RNA sequencing was performed to determine pathways linked to adipogenesis phenotype. RESULTS: In undifferentiated MSCs, greater zinc finger protein (Zfp)423 protein content was observed in Ob- versus NW-MSCs. Adipocytes from Ob-MSCs were larger but fewer than adipocytes from NW-MSCs. RNA sequencing analysis showed that Zfp423 protein correlated with mRNA expression of genes enriched for cell cycle, MSC lineage specification, inflammation, and metabolism pathways. MSC proliferation was not different before differentiation but declined faster in Ob-MSCs upon adipogenic induction. CONCLUSIONS: Ob-MSCs have an intrinsic propensity for adipocyte hypertrophy and reduced hyperplasia during adipogenesis in vitro, perhaps linked to greater Zfp423 content and changes in cell cycle pathway gene expression.

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.