Key points For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross‐sectional area, strength and type II fibre‐type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Out of 34 participants, thirteen displayed clear benefit of MOD on muscle hypertrophy and sixteen showed clear benefit of MOD on muscle strength gains. This coincided with greater total RNA accumulation in the early phase of the training period, suggesting that ribosomal biogenesis regulates the dose–response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose‐dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis. Abstract Resistance‐exercise volume is a determinant of training outcomes. However not all individuals respond in a dose‐dependent fashion. In this study, 34 healthy individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3) years) performed moderate‐ (3 sets per exercise, MOD) and low‐volume (1 set, LOW) resistance training in a contralateral fashion for 12 weeks (2–3 sessions per week). Muscle cross‐sectional area (CSA) and strength were assessed at Weeks 0 and 12, along with biopsy sampling (m. vastus lateralis). Muscle biopsies were also sampled before and 1 h after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4–7.7% difference, all P < 0.05. This coincided with greater reductions in type IIX fibres from Week 0 to Week 12 (MOD, −4.6 percentage points; LOW −3.2 percentage points), greater phosphorylation of S6‐kinase 1 (p85 S6K1Thr412, 19%; p70 S6K1Thr389, 58%) and ribosomal protein S6Ser235/236 (37%), greater rested‐state total RNA (8.8%) and greater exercise‐induced c‐Myc mRNA expression (25%; Week 2, all P < 0.05). Thirteen and sixteen participants, respectively, displayed clear benefits in response to MOD on muscle hypertrophy and strength. Benefits were associated with greater accumulation of total RNA at Week 2 in the MOD leg, with every 1% difference increasing the odds of MOD benefit by 7.0% (P = 0.005) and 9.8% (P = 0.002). In conclusion, MOD led to greater functional and biological adaptations than LOW. Associations between dose‐dependent total RNA accumulation and increases in muscle mass and strength point to ribosome biogenesis as a determinant of dose‐dependent training responses.

Background Lifestyle therapy with resistance training is a potent measure to counteract age‐related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those with chronic diseases (e.g. chronic obstructive pulmonary disease, COPD) and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored. Methods Ninety‐five male and female participants (healthy, n = 71; COPD, n = 24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double‐blinded manner (latitude 61°N, September–May). Seventy‐eight participants completed the RCT, which was initiated by 12 weeks of supplementation‐only (two weeks with 10 000 IU/day, followed by 2000 IU/day), followed by 13 weeks of combined supplementation (2000 IU/day) and supervised whole‐body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (nvariables = 7), endurance performance (n = 6), and muscle mass (n = 3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health‐related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments. Results Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%), and endurance performance (one‐legged, 23% ± 15%; whole‐body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, −6% ± 21%; [LDL]serum, −4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, −3% points), myonuclei per fibre (30% ± 65%), total RNA/rRNA abundances (15%/6–19%), and transcriptome profiles (e.g. 312 differentially expressed genes). Vitamin D3 supplementation did not affect training‐associated changes for any of the main outcome domains, despite robust increases in [25(OH)D]serum (∆49% vs. placebo). No conditional effects were observed for COPD vs. healthy or pre‐RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue and strength gains in participants with high fat mass, which advocates further study. Conclusions Vitamin D3 supplementation did not affect muscular responses to resistance training in older adults with or without COPD.

Background Subjects with chronic obstructive pulmonary disease (COPD) are prone to accelerated decay of muscle strength and mass with advancing age. This is believed to be driven by disease-inherent systemic pathophysiologies, which are also assumed to drive muscle cells into a state of anabolic resistance, leading to impaired abilities to adapt to resistance exercise training. Currently, this phenomenon remains largely unstudied. In this study, we aimed to investigate the assumed negative effects of COPD for health- and muscle-related responsiveness to resistance training using a healthy control-based translational approach. Methods Subjects with COPD (n = 20, GOLD II-III, FEV1predicted 57 ± 11%, age 69 ± 5) and healthy controls (Healthy, n = 58, FEV1predicted 112 ± 16%, age 67 ± 4) conducted identical whole-body resistance training interventions for 13 weeks, consisting of two weekly supervised training sessions. Leg exercises were performed unilaterally, with one leg conducting high-load training (10RM) and the contralateral leg conducting low-load training (30RM). Measurements included muscle strength (nvariables = 7), endurance performance (nvariables = 6), muscle mass (nvariables = 3), muscle quality, muscle biology (m. vastus lateralis; muscle fiber characteristics, RNA content including transcriptome) and health variables (body composition, blood). For core outcome domains, weighted combined factors were calculated from the range of singular assessments. Results COPD displayed well-known pathophysiologies at baseline, including elevated levels of systemic low-grade inflammation ([c-reactive protein]serum), reduced muscle mass and functionality, and muscle biological aberrancies. Despite this, resistance training led to improved lower-limb muscle strength (15 ± 8%), muscle mass (7 ± 5%), muscle quality (8 ± 8%) and lower-limb/whole-body endurance performance (26 ± 12%/8 ± 9%) in COPD, resembling or exceeding responses in Healthy, measured in both relative and numeric change terms. Within the COPD cluster, lower FEV1predicted was associated with larger numeric and relative increases in muscle mass and superior relative improvements in maximal muscle strength. This was accompanied by similar changes in hallmarks of muscle biology such as rRNA-content↑, muscle fiber cross-sectional area↑, type IIX proportions↓, and changes in mRNA transcriptomics. Neither of the core outcome domains were differentially affected by resistance training load. Conclusions COPD showed hitherto largely unrecognized responsiveness to resistance training, rejecting the notion of disease-related impairments and rather advocating such training as a potent measure to relieve pathophysiologies. Trial registration: ClinicalTrials.gov ID: NCT02598830. Registered November 6th 2015, https://clinicaltrials.gov/ct2/show/NCT02598830

Key points For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross‐sectional area, strength and type II fibre‐type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Out of 34 participants, thirteen displayed clear benefit of MOD on muscle hypertrophy and sixteen showed clear benefit of MOD on muscle strength gains. This coincided with greater total RNA accumulation in the early phase of the training period, suggesting that ribosomal biogenesis regulates the dose–response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose‐dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis. Abstract Resistance‐exercise volume is a determinant of training outcomes. However not all individuals respond in a dose‐dependent fashion. In this study, 34 healthy individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3) years) performed moderate‐ (3 sets per exercise, MOD) and low‐volume (1 set, LOW) resistance training in a contralateral fashion for 12 weeks (2–3 sessions per week). Muscle cross‐sectional area (CSA) and strength were assessed at Weeks 0 and 12, along with biopsy sampling (m. vastus lateralis). Muscle biopsies were also sampled before and 1 h after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4–7.7% difference, all P < 0.05. This coincided with greater reductions in type IIX fibres from Week 0 to Week 12 (MOD, −4.6 percentage points; LOW −3.2 percentage points), greater phosphorylation of S6‐kinase 1 (p85 S6K1Thr412, 19%; p70 S6K1Thr389, 58%) and ribosomal protein S6Ser235/236 (37%), greater rested‐state total RNA (8.8%) and greater exercise‐induced c‐Myc mRNA expression (25%; Week 2, all P < 0.05). Thirteen and sixteen participants, respectively, displayed clear benefits in response to MOD on muscle hypertrophy and strength. Benefits were associated with greater accumulation of total RNA at Week 2 in the MOD leg, with every 1% difference increasing the odds of MOD benefit by 7.0% (P = 0.005) and 9.8% (P = 0.002). In conclusion, MOD led to greater functional and biological adaptations than LOW. Associations between dose‐dependent total RNA accumulation and increases in muscle mass and strength point to ribosome biogenesis as a determinant of dose‐dependent training responses.

Background: Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those chronically diseased (e.g. chronic obstructive pulmonary disease, COPD), and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored. Methods: Ninety-five male and female participants (healthy, n=71; COPD, n=24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double-blinded manner (latitude 61°N, September-May). Seventy-eight participants completed the RCT, which was initiated by 12 weeks of supplementation-only (in average, 3333 IU.day-1), followed by 13 weeks of combined supplementation (2000 IU.day-1) and supervised whole-body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (n=7), endurance performance (n=6), and muscle mass (n=3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health-related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments. Results: Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%) and endurance performance (one-legged, 23% ± 15%; whole-body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, -6% ± 21%; [LDL]serum, -4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, -3%-points), myonuclei.fibre-1 (30% ± 65%), total RNA/rRNA abundances (15%/6-19%), and transcriptome profiles (e.g. ~336 differentially expressed genes). Vitamin D3 supplementation led to robust increases in [25(OH)D]serum (Δ49% vs placebo), but did not affect training-associated changes for any of the main outcome domains, with no interaction being evident with disease status or pre-RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue, strength gains in participants with high fat mass, and [cortisol]serum (Δ20%), all of which advocate further study. Conclusions: Vitamin D3 supplementation did not affect muscular responses to resistance training in old adults with or without COPD.