Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.05.08.652615

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

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.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Soendenbroe, C., Andersen, J. L., Heisterberg, M. F., Kjaer, M., Mackey, A. L.. 2025-05-13. Heavy Resistance Exercise Training in Older Men: A Responder and Inter-individual Variability Analysis. https://doi.org/10.1101/2025.05.08.652615

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

28S-rsRNA facilitates PASMC proliferation through PKM2 β-hydroxybutyrylation

Ribosomal RNA-derived small RNAs (rsRNAs) are nucleic acid fragments originating from rRNA, the functions and roles of which in diseases remain incompletely understood. We identified 28S rsRNA-CTC_L20, an rsRNA whose expression is upregulated in hypoxic pulmonary artery smooth muscle cells (PASMCs) and in lung tissues of pulmonary hypertension (PH) models. In hypoxic cells, 28S rsRNA-CTC_L20 promotes PASMC proliferation, and its knockdown mitigates SuHx-induced pulmonary hypertension and vascular remodeling. Mechanistically, 28S rsRNA-CTC_L20 modulates {beta}-hydroxybutyrate (BHB) production by maintaining the stability of ketogenic enzyme mRNAs through its "CTGNNGG" motif. Elevated levels of BHB enhance the {beta}-hydroxybutyrylation modification at K166 of pyruvate kinase M2 (PKM2), increasing its activity and driving glycolysis to sustain proliferation. These results link ketone body metabolism to glycolysis in hypoxic cells and define an rsRNA-BHB-PKM2 {beta}-hydroxybutyrylation axis in PH. They also point to 28S rsRNA-CTC_L20 as a potential target for treating vascular remodeling.

physiology↗

Selective activation of estrogen receptors modulates electrical activity and insulin secretion in human EndoC-βH1 cells

Estrogen receptors (ERs), ER and ER{beta} have important roles in the physiology of the endocrine pancreas in animal models, but the effects of ER activation on insulin-secreting human cells are still poorly understood. Here, we investigated the role of ER and ER{beta} as modulators of electrical activity and insulin secretion in the insulin-secreting human cell line EndoC-{beta}H1. Immunocytochemical analysis revealed a widespread cellular distribution of ER, while ER{beta} was predominantly localized outside the nucleus. We observed that both estradiol (E2) and the ER{beta} agonist diarylpropionitrile (DPN) led to a decrease in insulin secretion in the absence of stimulatory glucose concentrations, without affecting insulin content. Patch-clamp experiments revealed that a 48-hour treatment with either the ER agonist PPT or DPN resulted in depolarization of the resting membrane potential, increased action potential firing frequency, and altered the action potential waveform in EndoC-{beta}H1 cells. PPT increased voltage-dependent Ca2+ channel currents, while DPN reduced K+ and Na+ currents. These results suggest that activation of ER and ER{beta} modulates beta-cell electrical activity through distinct pathways involving ion channels. The effects of E2, PPT, and DPN were not caused by altered expression levels of ion channel genes after 48 hours of treatment. This suggests that these receptors act extranuclearly without affecting gene expression. Together, our findings demonstrate that selective activation of ER and ER{beta} modulates beta-cell excitability through distinct electrophysiological mechanisms and that E2 and DPN reduce basal insulin secretion in human EndoC-{beta}H1 cells. These results support ER and ER{beta} as potential targets for modulating human pancreatic beta-cell function.

physiology↗

Body weight modifies the efficacy of lifespan-extending interventions in ad libitum-fed mice

Geroprotective interventions are often assessed by extension of lifespan in ad libitum-fed mice. Increased lifespan could therefore reflect rescue of adverse phenotypes of unhealthy controls. We analysed body weight and survival for 33,780 mice in the Interventions Testing Program (ITP) to test whether treatment effects varied with body weight. In males, each added standard deviation of attained adult weight made treatment 6% more favourable (HR 0.94), more apparent for interventions that lowered body weight (HR 0.90). Median lifespan increase rose from 6.2% in mice in the lightest quartile to 20.2% in the heaviest pre-dosing weight quartile among those experiments, mainly because control survival declined more steeply with weight than that of the intervention group. The effect of body weight was consistent across 13 of 14 compounds and reflected weight attained during adulthood rather than in early life. Weight-dependence of intervention effects was weak in ITP females, possibly because median survival of controls exceeded that of every sampled non-ITP female control group. Amelioration of weight-associated risk is therefore implicated as a major contributor to lifespan increases relative to heavy, short-lived controls. The geroprotective effects of these interventions may thus be less apparent in metabolically healthier mice or humans.

physiology↗