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PLoS ONEPhysiologyPeer-reviewed journal article

Heavy Resistance Exercise Training in Older Men: A Responder and Inter-individual Variability Analysis

Casper SoendenbroeiD, Jesper L. AnderseniD, Mette F. Heisterberg, Michael KjæriD, Abigail Louise MackeyiD

PDFDOIPreprint

Abstract

BackgroundHeavy resistance exercise training (HReT) effectively increases muscle mass and strength in groups of older individuals. However, the extent of inter-individual variability in response to HReT, and the possible existence of non-responders, remains unclear. The primary aim was to determine the presence of inter-individual variability in the response to prolonged HReT in healthy older individuals. Secondary aims were to classify individual responsiveness using a combination of gold-standard assessment methods, and to explore training progression and baseline levels as possible response moderators. MethodsWe conducted a secondary analysis of an 8- and 16-week intervention of thrice weekly HReT (EX) or continuation of a sedentary lifestyle (SED). 58 healthy men (age 72{+/-}5) were randomized into EX (n=38) or SED (n=20). Assessments were conducted at baseline, mid-intervention (8wk), and post-intervention (16wk) for five outcomes: Maximal voluntary contraction strength (MVC), rate of force development (RFD), quadriceps cross-sectional area (qCSA), and type I and II myofibre cross-sectional area (fCSA). Training compliance and progression (as measured by 1-repetition maximum (1RM)) were monitored. Inter-individual variability was assessed using the standard deviation of individual responses (SDIR). Individual change scores relative to a Typical Error (TE) were used to classify individuals as Poor, Trivial, Robust or Excellent responders. ResultsAt the group level, EX increased MVC, RFD, qCSA and type II fCSA by 19{+/-}14 %, 58{+/-}80 %, 3{+/-}4 % and 14{+/-}25 %, respectively, with no changes in SED. Inter-individual variability was observed for all outcomes. Individual responses to HReT were outcome- and time-dependent, with 31 participants (82%) being classified as Robust or Excellent responders, and two participants (5%) being Poor responders, following 16wk of HReT. Training compliance and 1RM progression did not account for the observed response variability following HReT. Lower baseline levels were associated with greater improvements; however, this did not account for the observed inter-individual variability. ConclusionsThis study provides strong evidence of inter-individual variability in response to HReT among healthy older men. Given the rarity of true non-responders, HReT should remain the universally recommended first-line strategy for enhancing muscle mass and strength in this population.

In-depth summary

Claude Opus 5.5 · xhigh effort · 8 Nov 2026 · from the full text of version 1 (13 May 2025) · CC BY 4.0

Sixteen weeks of heavy resistance exercise in older men produces true inter-individual variability, yet multi-outcome classification shows 82% respond robustly or excellently and only 5% respond poorly.

Apparent variability in muscle mass and strength gains after resistance training in older adults often conflates true treatment heterogeneity with measurement error and biological fluctuation. Using a non-exercising control group and four structural and functional outcomes, this study isolates intervention-induced variability and demonstrates that true non-responders are rare.

Key results

  1. ShownHeavy resistance exercise training significantly increased group-level isometric strength, rapid force generation, whole-muscle cross-sectional area, and fast-twitch fiber size over 16 weeks compared with sedentary controls.

    In the exercise group (n=38, ~95% compliance over 48 sessions), maximal voluntary contraction (MVC) increased by 19.4 +/- 14.0%, rate of force development (RFD) by 58.4 +/- 79.5%, quadriceps cross-sectional area (qCSA) by 3.4 +/- 3.6%, and type II myofibre cross-sectional area (fCSA) by 14.2 +/- 24.9% at 16 weeks, with no significant group changes in controls (n=20). · Abstract; 3.2. Effectiveness of HReT at group level; Tables

  2. ShownTrue intervention-induced inter-individual response variability was present across the majority of strength and hypertrophy outcomes at both 8 and 16 weeks.

    A positive standard deviation of individual responses (SDIR, where exercise group change SD exceeded sedentary control change SD) occurred in 4 of 5 outcomes at 8 and 16 weeks across all participants, and in 4 of 5 (8 weeks) and 5 of 5 outcomes (16 weeks) among losartan-treated participants only. · Abstract; 3.3. HReT inter-individual variability at the…; Tables

  3. ShownIntegrating four hypertrophy and strength outcomes relative to control-group typical errors classified 82% of older men as robust or excellent responders by 16 weeks.

    Multi-outcome classification across MVC, RFD, qCSA, and type II fCSA categorized 16 (42%) and 15 (39%) participants as Robust and Excellent responders at 16 weeks, while Poor and Trivial responders declined from 32% (3 Poor [8%], 9 Trivial [24%]) at 8 weeks to 18% (2 Poor [5%], 5 Trivial [13%]) at 16 weeks. · Abstract; 3.5. Responder classification; 4. Discussion; Figure legends

  4. ShownLower baseline strength and fast-twitch fiber size correlated with larger relative training gains, whereas 1-repetition maximum progression did not differentiate responder classes.

    Baseline levels correlated negatively with 16-week percentage gains in type II fCSA (R^2 = 0.29, p < 0.005), MVC (R^2 = 0.29, p < 0.0005), and RFD (R^2 = 0.40, p < 0.0001), while mixed-effects models across sessions 1, 7, 16, 25, 34, and 43 showed no session-by-responder interaction for 1RM. · Abstract; 3.6.1. Training progression; 3.6.2. Baseline levels; Figure legends

Methods, data and reproducibility

Secondary analysis of a 16-week randomized controlled trial in 58 older men comparing thrice-weekly heavy resistance exercise training against sedentary controls across five strength and hypertrophy outcomes (dynamometry, thigh MRI, and muscle biopsy ATPase histology). Global response variability was quantified via the standard deviation of individual responses and classified against control typical errors.

  • Healthy normotensive non-smoking older men (age 72 +/- 5 years, BMI 19-34 kg/m^2) randomized to heavy resistance exercise (EX) or sedentary lifestyle (SED) in Copenhagen · human · n = 58 (EX n=38, SED n=20)
Methods & tools
OsiriX 8.5, Prism v.10, Microsoft Excel, Kinetic Communicator 500-11, Philips Ingenia 3.0 T scanner
Reagents & environment
OsiriX 8.5 (Pixmeo SARL); Prism v.10 (GraphPad Software); Excel (Microsoft) [S9, S15].
Reproducibility gaps
No public code or individual-level data repositories are provided; raw outcome group means were published in prior primary trial reports [S8-S11].
Limitations (3)
  • This was a secondary analysis of a trial in which all 20 sedentary controls and 20 of 38 exercising participants received daily losartan (50-100 mg), leaving no placebo-sedentary control group [S3, S5, S7, S27]. · stated by the authors
  • One participant classified as a Poor responder exhibited an implausible 5% decline in quadriceps cross-sectional area over 16 weeks (already present at 8 weeks), suggesting a baseline MRI scan error not prevented by control-group adjustment [S27]. · stated by the authors
  • The cohort was restricted to healthy, normotensive, non-smoking older men aged 64 years or above from a single center, excluding women and frail or diseased older adults [S3, S4]. · noted in this summary

Read this if you design exercise physiology interventions or analyze inter-individual treatment response variability against control-group typical errors in human cohorts.

Citations
7
FWCI
47.30
Field percentile
top 1%

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