The Inter-Individual Variation in Resistance Training Response Conference was hosted at the University of Jyväskylä, Finland November 19-21, 2025. This paper summarizes key themes that emerged across lectures and discussions. First, resistance training induces multidimensional adaptations at the tissue, muscle fiber, and ultrastructural levels, including radial muscle fiber hypertrophy through increased myofibril number, longitudinal growth through sarcomere addition throughout the length (not ends) of muscle fibers, and metabolic adaptations that emulate other models of rapid cell growth. Second, training program variables including weekly sets, volume-load, rest interval duration, and training proximity to failure meaningfully influence hypertrophic outcomes in the general population, whereas exercise selection can be flexible. Third, age as well as molecular signatures before and in response to training influence interindividual response heterogeneity. Finally, while interindividual variability in observed hypertrophic responses is considerable, delineating true inter-individual variability from random variation remains challenging. Hence, study design considerations that can be thoughtfully applied to enhance rigor include repeat validation trials, unilateral within-subject designs, minimum clinically important difference thresholds, and multivariate composite responder classifications. This paper aims to summarize conference highlights while also providing meaningful implications for both researchers and practitioners and advancing current thinking on heterogeneity in the resistance training response.

The American College of Sports Medicine has included a description of the components of physical fitness (PF) in their publications for 40 yr. Because new scientific evidence has emerged, the American College of Sports Medicine convened a scientific roundtable to reexamine the components of PF. The scientific roundtable agreed upon standardized definitions and an updated evidence-informed model of PF consisting of five interconnected components of PF: 1) cardiorespiratory fitness, 2) muscular fitness, 3) body composition, 4) neuromotor fitness, and 5) flexibility, with muscular fitness, body composition, and neuromotor fitness further separated into subcomponents. These components met four inclusion criteria: they 1) are changeable by exercise, 2) affect the ability to participate in physical activity or exercise, 3) contribute to health, and 4) can be feasibly assessed in professional practice. Additional overriding themes that emerged from the scientific roundtable included the complexity of PF and the interrelated nature of the components. Furthermore, it was agreed that when applied in practice, PF is best addressed in an individualized manner. Therefore, the components of PF should be considered dynamic as the focus on any given component can shift when considering individual needs, goals, health status, and priorities/interests.

BACKGROUND:The sit-to-stand (STS) test can assess physical function in people with chronic obstructive pulmonary disease (COPD); however, there are multiple versions. No study has used current guidelines to assess the measurement properties of the STS tests in people with COPD. METHODS:We conducted a systematic review using current COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. Full text peer-reviewed publications were included if they assessed the measurement properties (validity, reliability and/or responsiveness) of at least one STS test among community-dwelling people with COPD. We searched six databases and imported results into Covidence where title/abstract screening and full text selection was completed independently and in duplicate. Extraction was conducted independently and in duplicate using the COSMIN extraction file. We assessed study risk of bias (very good, adequate, doubtful or inadequate), measurement property quality (sufficient, indeterminate or insufficient) and overall certainty of evidence (high, moderate, low or very low) using the COSMIN recommended tools. RESULTS:We assessed 2577 titles/abstracts and 102 full texts for inclusion; 30 publications met eligibility. Seven unique STS tests were located with the most common being the 1 min STS test (n=14, 39%), 5-repetition STS test (n=10, 28%) and the 30 s STS test (n=8, 22%). Where assessed, reliability was sufficient for the 1 min, the 5-repetition and the 30 s STS tests. Only the 1 min STS test had high-quality evidence of sufficient construct validity, while the 30 s STS test was the sole test with at least moderate quality evidence of sufficient responsiveness. CONCLUSIONS:The 1 min STS test has the most robust measurement properties for cross-sectional assessments while the 30 s STS test is more robust to assess change.

AIM:We investigated the influence of MCPBT on muscle hypertrophy and strength in response to RET over three MCs. METHODS:Employing a randomized, unilateral design, twenty-four healthy, eumenorrheic females completed a within-participant resistance training trial across three consecutive MCs (12.2 ± 1.3 weeks; mean ± SD). Each individual's legs were randomly assigned to one of four conditions: non-exercising control (CON), continuous exercise training (balanced across both MC phases; EX), high-volume in the follicular phase with low volume in the luteal phase (HV-FOL), or the converse (HV-LUT). HV was defined as five sets per exercise twice weekly (≥10 sets·muscle⁻¹·week⁻¹), and low volume comprised one set per exercise twice weekly (≤5 sets·muscle⁻¹·week⁻¹). The primary outcome was thigh lean mass via dual-energy x-ray absorptiometry. Secondary outcomes were vastus lateralis cross-sectional area (VL CSA), leg fat-free mass (FFM) via bioelectrical impedance analysis, one-repetition maximum (1RM) strength and maximal voluntary isometric contraction. RESULTS:All RET conditions produced greater gains than CON for thigh lean mass, VL CSA, FFM, and 1RM strength (all, p < 0.001), with no differences (all, p ≥ 0.17) between any of the training conditions (EX, HV-FOL, and HV-LUT). CONCLUSIONS:MCPBT confers neither hypertrophy nor strength advantages over traditional continuous RET. Training volume-load, not MCPBT, was associated with several adaptations. MC phase-based adjustments in RET could be based on individual preference but are not necessary to achieve muscular adaptations to RET.

BACKGROUND AND PURPOSE:Strength training is recommended after stroke to retain strength and function. Muscle power is important for mobility, presenting an opportunity for power training programs. The objectives of this study were to (1) determine the feasibility and (2) effects of the power exercise for stroke recovery (POWER) intervention in people with mild to moderate chronic stroke. METHODS:This was a single-group trial in people with mild to moderate chronic stroke (modified Rankin Scale < 4). The POWER intervention was delivered in a community-based gym over 3 phases: familiarization (week 1), strength (weeks 2-5), and power (weeks 6-10), where repetitions were performed as quickly as possible. Feasibility was the primary outcome, measured using preestablished indicators. Effects were measured with the timed up and go test, short physical performance battery, 30-second chair stand test, fast-paced walking speed, isokinetic strength, power, and the stroke impact scale. RESULTS:Fifteen people (61.5 years, 4.9 years poststroke, n = 7 female) were recruited within 6 months. Attendance was high (96%), with minimal attrition (n = 1) and no serious adverse events or exaggerated blood pressure responses to exercise. Most (71%) exercise sets were adhered to. There were improvements in timed up and go performance (-1.6 seconds [95% confidence interval, CI: -0.6, -2.6]), short physical performance battery (+0.9, 95% CI: 0.1, 1.8), fast-paced walking (+0.1 m/s, 95% CI: 0.01, 0.2), and the 30-second chair stand test (+3.0, 95% CI: 1.7, 4.2). There were also moderate to large improvements in muscle strength, power, and health-related quality of life. DISCUSSION AND CONCLUSIONS:POWER was feasible and shows potential effects on muscle strength, power, physical function, and health-related quality of life in community-dwelling people with mild to moderate chronic stroke.

Abstract The effects of high‐load (HL) versus high‐volume (HV) resistance training (RT) on various molecular outcomes are similar. However, mitochondrial responses remain understudied. Therefore, the purpose of this study was to interrogate mitochondrial mRNA and protein responses to acute and chronic HL versus HV RT. Vastus lateralis biopsies from resistance trained males in two prior studies were assessed. In Study 1, 11 college‐aged men completed an acute bout of either HL or HV RT exercises to failure. Biopsies were collected at PRE, 3‐h post‐, and 6‐h post‐exercise. In Study 2, 15 college‐aged men participated in 6 weeks of supervised unilateral RT where each leg was assigned to either HL or HV RT. Biopsies were collected from both legs prior to and 72 h following last training bout of the intervention. Biopsies from both studies were used to assess mitochondrial mRNAs, and Study 2 biopsies were assayed for mitochondrial proteins and citrate synthase (CS) activity. Results from both studies revealed several significant main effects of time but no significant interactions. Additionally, CS activity, a surrogate of mitochondrial content, decreased following chronic RT (P = 0.016) but no interaction was observed between the HV and the HL leg over time (P = 0.882). In conclusion, while RT resulted in both acute mitochondrial mRNA and chronic CS activity and mitochondrial protein responses, there were no differences in the HL versus HV paradigms on these outcomes.

Mitochondrial subcellular area influences function. Muscle disuse reduces mitochondrial content; however, its effect on mitochondrial subcellular location is unclear. Omega-3 fatty acid (n-3) attenuates declines in muscle mass and mitochondrial function during disuse; however, whether n-3 supplementation prevents the decline in mitochondrial content has not been examined. We investigated the effects of 2 weeks of leg immobilization followed by 2 weeks of remobilization on skeletal muscle mitochondrial content and subcellular localization with and without n-3 supplementation. Twenty healthy females supplemented with n-3 (2.97 g EPA and 2.03 g DHA) or control (isoenergetic sunflower oil) during 2 weeks of unilateral leg immobilization and 2 weeks of remobilization. Vastus lateralis biopsies were taken for electron microscopic analysis of mitochondrial content. Subsarcolemmal (SS) mitochondrial content decreased during immobilization (control: -9%, n-3: -66%, p = 0.009) and remained lower following recovery (control: -41%, n-3: -42%, p = 0.005). This effect was driven by the n-3 group (p < 0.02). Intermyofibrillar (IMF) mitochondrial content did not decline during immobilization, but was lower than baseline following recovery in the central (p = 0.01) IMF. The effects of leg immobilization on mitochondrial content differ by location, are not reversed with short-term recovery, and are influenced by n-3 supplementation.

Skeletal muscle metabolic and physical capacities are influenced by both genetics and load status and decline with age. Recent advances in sequencing have detailed cell types at unprecedented detail; yet these approaches do not scale to adequately model human muscle physiological heterogeneity. We produced a powerful resource for ageing studies, including consistent deep transcriptomic profiles of 1,675 human muscle biopsies (∼28,000 genes per profile) and multiple single-cell spatial transcriptomic technologies. We present several novel models of tissue ageing. Five Quantitative network models (QNMs), built using >40 trillion calculations and 930 human muscle transcriptomes, modelled aging and the influence of load status. Additional differential expression (DE) signatures for atrophy, hypertrophy and cardio-respiratory adaptation were integrated with single-cell RNAseq and cell-specific bulk profiles to reveal cell-enriched modules and the topology of human skeletal aging. Rapamycin transcriptomes from cultured muscle and endothelial cells, along with in vivo signatures for insulin resistance and sex, were integrated into these analyses. We show that >3,000 genes are DE with muscle age (equally up and down); that a novel pre-frailty signature in elderly subjects has a remarkably strong overlap with the response of healthy muscle during experimental atrophy and that the hypertrophy signature in elderly muscle, but not young muscle, opposes the age-regulated transcriptome. We report that non-responders for hypertrophy or gains in cardio-respiratory capacity have highly distinct genome-level response to exercise. QNM revealed cell-specific processes in endothelial cells and fibroblasts, including novel interactions between insulin sensitivity, age and senescence. From two hundred and eighty-six hub genes consistent in both young and old muscle network models, 27% had known roles in muscle biology, while of the top 50 hub genes (45% protein coding), 80% were newly linked to human muscle biology, including ARHGAP4, CEP131 and IFITM10 and many short- and long-noncoding RNAs. Many genes demonstrated extreme changes in topology in old muscle, such as the neddylation and aging linked gene, DCUN1D5. GeoMX-based spatial muscle fibre-type profiling (57 regions), along with Xenium (8 regions) and Merscope (54 regions) single-cell spatial technologies located key aging, frailty and load-responsive genes to individual cell types and provided novel insight into the location of autocrine/paracrine secreted factors such as GDNF, while IL6 was located to rare endothelial cells. A machine-learning model ranked the factors most associated with the topological changes with age. This prioritised network features over DE signatures, highlighting positive correlating edges to down-regulated genes during atrophy, genes up-regulated by Rapamycin and both positive and negative correlating insulin sensitivity features, along with gene hub status, best explained muscle ageing. Genome level modelling produced an independently validated transcriptomic 'age clock' and found it to be invariant to muscle load status in people >50y, while we revealed novel interactions between gene length and age. Release of an unprecedented level of consistently aligned genomic data, along with QNMs with >7,000 searchable modules, provides a powerful resource for the aging research communities.

Adults aged ≥ 80 years experience the highest rates of fall-related injury and mortality, yet remain underrepresented in prospective fall research. Although reduced muscle strength is recognised as a risk factor for falls, prospective evidence linking muscle strength to severe fall injuries in the oldest old remains limited. This prospective cohort study included 3059 individuals aged ≥ 80 years from the fourth Trøndelag Health Study (HUNT4) 70 + Survey in Norway. Using sex-specific reference values, handgrip and leg strength were classified as strong, moderately reduced, or reduced. Cox proportional hazards regression was used to examine associations between strength categories and severe fall injuries, ascertained from national health registries. Baseline median age was 84 years (interquartile range 82–89; 59

BACKGROUND:Resistance training (RT) is increasingly recognized as a promising exercise modality for enhancing health and fitness in children and adolescents. However, evidence remains inconsistent in those with overweight/obesity. This umbrella review synthesized evidence from systematic reviews to evaluate RT effects on body composition, physical fitness, and cardiometabolic health in this population. METHODS:We searched seven databases from inception to February 2026 for systematic reviews with meta-analyses comparing RT versus controls in children and adolescents with overweight/obesity. Main outcomes included percent body fat, fat-free/lean mass, muscular strength, cardiorespiratory fitness, and cardiometabolic markers. We conducted meta-analyses on unique primary data, with subgroup analyses by comparator type (active vs. inactive), training frequency (1-2 vs. ≥ 3 sessions/week), duration (≤ 12 vs. > 12 weeks), and age (≤ 12 vs. > 12 years). RESULTS:Sixteen systematic reviews (67 primary studies, 5112 participants) were included. Compared with all non-RT control conditions, RT decreased percent body fat (mean difference [MD]: -0.53%; 95% confidence interval [CI]: -1.00 to -0.06) and increased fat-free/lean mass (MD: 0.48 kg; 95% CI: 0.23 to 0.74). Muscular strength also improved significantly, with consistent benefits across body regions, training frequencies, durations, and age groups. Subgroup analyses indicated significant improvements in cardiorespiratory fitness, visceral fat, and fasting insulin versus inactive controls. CONCLUSION:This umbrella review demonstrates that RT significantly improves body composition and physical fitness in children and adolescents with overweight/obesity, alongside modest cardiometabolic health benefits. Our findings support integrating RT into school- and community-based programs for pediatric obesity management.

Abstract Endurance (END) or resistance exercise (RE) training results in adaptations that give rise to distinct skeletal muscle phenotypes. Hallmarks of RE include increases in muscle fibre and muscle cross-sectional area and strength, whereas END increases mitochondrial content. Such distinct phenotypes arise from differential metabolic and mechanical signal transduction, transcriptional, and protein translation pathways, culminating in exercise mode-specific adaptations in the muscle proteome. However, little empirical data exist on the protein-specific dynamic responses underlying training-mode-specific adaptations in humans. Using a model of unilateral exercise combined with stable isotope labelling with deuterium oxide, we measured changes in synthesis and abundance from baseline and during early (week 1) and later (week 10) periods of adaptation to END and RE training in young healthy adults (n = 14; 8 female, 6 male; 20 ± 1 y, 70 ± 10 kg). We quantified changes in the abundance (n = 1146 proteins) and synthesis (n = 247 proteins) profiles of skeletal muscle across a 5-day pre-training baseline period and during early and later adaptation to RE and END. Abundance profiling revealed mode-specific proteome remodelling, whereby RE increased ribosomal and contractile protein networks, whereas END increased mitochondrial inner membrane proteins after 10 weeks of training. The protein-specific synthesis rates of 119 proteins showed training-induced differences (P < 0.1 and log2 fold change > 1), including subsets of structural proteins that responded differently to RE and END training modes. Notably, distinct Z-disc proteins, such as XIRP1 (RE-specific) and LDB3 (END-specific), exhibited mode-specific regulation despite sharing a similar subcellular localisation. We report, for the first time, that divergent phenotypic adaptations to RE and END extend beyond changes in bulk fraction-specific synthesis rates and are regulated by training-mode-specific adaptations in distinct protein subsets within similar subcellular protein locations.

PURPOSE:The aim of this overview of reviews was to determine the impact of resistance training (RT) prescription on muscle function and hypertrophy, utilizing evidence synthesis methods. It updates the American College of Sports Medicine 2009 Position Stand, "Progression models in resistance training for healthy adults." DATA SOURCES:Ovid MEDLINE(R) ALL, Ovid Emcare, Ovid Embase, Cochrane Database of Systematic Reviews, EBSCOhost SPORTDiscus, and Web of Science Core Collection current to October 2024. ELIGIBILITY CRITERIA:Eligible systematic reviews synthesized randomized trials of healthy adults (≥18 yr) who completed RT (≥6 wk; range: 6-52 wk), compared with a group that completed no exercise or an alternative RT program, and reported the change in muscle function, size, or physical performance. RESULTS:We synthesized data from 137 systematic reviews (>30,000 participants). Compared with no exercise (control), RT significantly improved muscle strength, size (hypertrophy), power, endurance, contraction velocity, gait speed, balance, and multiple physical function outcomes. Few RT prescription (RTx) variables affected primary adaptations. However, voluntary strength was enhanced by lifting heavier loads (≥80% one-repetition maximum), through a complete range of motion, for 2-3 sets, at the beginning of training sessions, and ≥2 sessions/wk. Muscle hypertrophy was enhanced by higher volumes (≥10 sets/wk) and eccentric overload. Power was enhanced by moderate loads (30%-70% one-repetition maximum), low-to-moderate volume (≤24 repetitions⋅sets), Olympic-style weightlifting, and power RT (fast concentric phase). Power RT enhanced physical function. Training to momentary muscle fatigue, equipment type, exercise complexity, set structure, time under tension, blood flow restriction, and periodization did not consistently impact training outcomes. CONCLUSIONS:Healthy adults should perform progressive RT, with variable prescription consistent with our findings, to improve muscle function, size, and physical performance. Muscle strength, hypertrophy, power, and certain components of physical function can be enhanced by manipulating the RT variables highlighted.

BACKGROUND:The prognostic value of obesity in cardiovascular disease is complex. Measures such as body mass index and waist-to-height ratio show differing associations with outcomes, especially in heart failure. Assessing sarcopenic obesity, the coexistence of excess fat and low muscle mass, may clarify this relationship; however, quantifying sarcopenia in clinical practice remains challenging. OBJECTIVES:The goal was to establish a translatable method of assessing sarcopenic obesity from cardiovascular imaging and assess its clinical relevance using long-term follow-up, genomic, and transcriptomic data. METHODS:We developed a deep learning pipeline to quantify pectoralis major muscle mass from 55,768 cardiovascular magnetic resonance examinations and combined this with body weight to derive a novel sarcopenic obesity index. Associations with cardiac remodeling phenotypes and adverse cardiovascular and mortality outcomes were tested in multivariable models. Genome-wide association analysis, colocalization, and polygenic risk score evaluation were performed for the sarcopenic obesity index. Transcriptomic profiling of skeletal muscle across 7 pathophysiological states assessed differential gene expression. RESULTS:A higher sarcopenic obesity index was associated with adverse cardiac remodeling, and with increased risk of incident heart failure (HR: 1.31; 95% CI: 1.16-1.49), cardiovascular death (HR: 1.51; 95% CI: 1.25-1.81), and all-cause mortality (HR: 1.37; 95% CI: 1.26-1.49). Genome-wide association analysis identified 16 loci for sarcopenic obesity. Loci included genes associated with heart failure and nonischemic cardiomyopathy, with colocalization implicating shared causal variants in heart failure. Transcriptomic profiling demonstrated that sarcopenic obesity loci were specifically modulated during muscle atrophy. Analyses identified ACVR2B, the target of bimagrumab, which is being tested with semaglutide to enhance fat loss while maintaining lean mass. CONCLUSIONS:These results establish sarcopenic obesity as a clinically meaningful cardiovascular risk phenotype and point to viable therapeutic targets.

Resistance training (RT) is an effective intervention for improving muscle health and metabolism in ageing, but the degree of responsiveness (hypertrophy) to RT varies substantially. We examined muscle metabolomic profiles before and after 10-weeks RT in older adults classified into upper (UPPER) and lower (LOWER) tertiles of hypertrophy to identify key metabolic adaptation differences. Fifty older adults (23 males, 27 females, mean 68.2 years old) completed 10 weeks of RT combined with whey protein supplementation. Quadriceps cross-sectional area (CSA) was assessed via magnetic resonance imaging before and after RT. Participants were grouped into UPPER (n = 25, 10.3 ± 2

IntroductionMany survivors of critical illness experience lasting physical disability. Post-hospital rehabilitation has the potential to reduce this physical disability; however, primary studies have reported inconsistent results. We aimed to answer the following question: Among community-dwelling adults who survived critical illness, does participation in post-hospital physical rehabilitation, compared with no rehabilitation or alternative non-physical interventions, improve physical functioning 12 months after discharge from acute care?Materials and methodsThis is a systematic review protocol that was registered with PROSPERO (CRD 420251174065). It will be conducted with Cochrane methods and reported according to the 2020 Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. To optimize the impact of this review, our study team includes a patient partner to guide our methods and interpretation. To be eligible, peer-reviewed randomized controlled trials must have enrolled community-dwelling adults (≥ 18 years) previously admitted to the ICU (≥24 hours) to a post-hospital physical rehabilitation program compared to any control. Outcomes of interest include physical function, return to work, and health care utilization. We will search five databases from their inception. Study screening, selection and extraction will be conducted independently and in duplicate using Covidence. Disagreements will be resolved through discussion or with a third reviewer. We will assess risk of bias using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Where appropriate, we will conduct meta-analyses using random-effects modeling. Certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).ConclusionA recent international multiprofessional expert panel highlighted the importance of understanding how follow-up care models can optimize long-term recovery after critical illness. Our review will provide a comprehensive synthesis of the impact of post-hospital rehabilitation on long-term recovery of survivors of critical illness.

The essentiality of protein in the human diet is unequivocal. Yet researchers, clinicians, and lay people often believe numerous propositions about dietary protein despite insufficient supporting or refuting data in some instances. To address this disconnect, and to "pressure-test" current beliefs about dietary protein, the Indiana University School of Public Health-Bloomington convened a workshop in February 2025 titled "Human Dietary Protein Needs and Benefits: A Critical Assessment of Postulated Propositions." More than 20 international experts discussed (1) methodologic issues affecting data acquisition and interpretation; (2) "optimal" dietary protein intakes and effects on muscle protein synthesis rates, muscle protein accretion, muscle growth, and muscle repair; (3) protein needs during weight loss; (4) acute protein intake thresholds above and below which protein is no longer related to anabolism; and (5) dietary protein intakes above which protein may be detrimental to health. The experts rated each proposition on a scale from "existing evidence strongly supports the proposition" to "existing evidence seems sufficient to rule out the viability of the proposition." In most instances, the experts believed additional research was warranted. For many propositions the research base was insufficient in terms of quality (rigor), quantity (sample size, study duration), or pertinence (e.g., use of surrogate markers).