Schoenfeld, B. J. | bioRxiv Science

bioRxiv2026

Aging concomitantly reduces skeletal muscle proteome plasticity and hypertrophic responses to resistance training

Skeletal muscle mass and training adaptations decline with aging, yet the proteomic basis of these attenuated responses remains unclear. We hypothesized that aging is accompanied by diminished proteome plasticity in response to resistance training (RT). The soluble proteome of VL biopsies was profiled in 17 younger (21.9 {+/-} 2.5 yr) and 15 older (57.5 {+/-} 6.9 yr) untrained males before and after 10-12 weeks of supervised RT using data-independent acquisition mass spectrometry (2,113 quantified proteins). At baseline, we detected 196 differentially expressed proteins (DEPs) significantly differed between age groups by {Pi}-score (278 by FDR). A 5.6-fold difference in training-responsive was observed in younger vs. older adults (100 vs. 18 {Pi}-score DEPs; 134 vs. 0 FDR-significant). Despite this quantitative attenuation, 61.6% of proteins changed in the same direction in both age groups (Spearman {rho} = 0.284, p = 3.46 x 10-), indicating conserved but amplitude-compressed training responses (median |log2FC|: 0.13 young vs. 0.09 old). RT in older adults partially reversed the aging proteome in that directionally different changes were observed in 75.2% of aging- or training-significant proteins in aging and training contrasts, with ribosomal and translational machinery showing the strongest reversal (cytoplasmic translation NES: -2.90 with aging, +2.60 with training). Ten WGCNA co-expression modules were identified, with age emerging as the dominant organizing principle (Turquoise module r-equiv = +0.59, p < 0.001). Module eigengenes discriminated age groups at the univariate level (Turquoise/Lipid Catabolism AUC = 0.96, q < 0.012), and training-induced module changes correlated with hypertrophic outcomes. Aging markedly attenuates but does not qualitatively alter skeletal muscle proteome plasticity. RT partially reverses aging proteome signatures, with translational machinery being the most responsive and mitochondrial programs the least responsive. Baseline proteomic state constrains adaptive capacity, suggesting that the molecular features distinguishing aging muscle directly may limit its hypertrophic response to RT.

physiology↗

bioRxiv2025

Resistance training-induced appendicular lean tissue mass changes are largely unrelated to pre-training bone characteristics in a larger cohort of untrained adults

We sought to determine if pre-intervention bone characteristics measured by dual-energy x-ray absorptiometry (DXA) were associated with changes in bone-free lean tissue mass following a period of resistance training in a large cohort of untrained adults (n=119, 62M/57F, 26.0{+/-}4.7 kg/m2, age range = 18-70 years old). Participants completed 10-12 weeks of supervised whole-body resistance training twice weekly, and DXA scans were obtained approximately the same time of day prior to the intervention and 48-72 hours following the final training bout. Associations between baseline skeletal measures (e.g., appendicular bone characteristics, shoulder and hip widths) and training induced changes in appendicular lean mass were examined by estimating correlations between participant-level random slopes (reflecting change over time) and baseline skeletal measures. The same approach was used to evaluate associations between other participant attributes (e.g., age, training volume-load, self-reported energy intake) and appendicular lean tissue mass changes. Modeling was also used to explore whether baseline skeletal characteristics (e.g., shoulder and hip widths) moderated the change in appendicular lean tissue mass from training. All analyses used a Bayesian framework, and interpretation focused on estimated effect sizes and their associated credible intervals rather than formal null hypothesis testing. Strong positive associations were observed between pre-intervention characteristics including dual-arm lean tissue mass and dual-arm bone mineral content (r=0.90), dual-leg lean tissue mass and dual-leg bone mineral content (r=0.86), dual-leg lean tissue mass and pelvic mineral content (r=0.73), and dual-arm lean tissue mass and shoulder width (r=0.76). In contrast, weak associations were observed between training-induced changes in appendicular lean tissue mass versus bone characteristics, training volume-load, self-reported energy intake, self-reported protein intake, BMI, and age (-0.08[≤]r[≤] 0.24). After adjusting for sex, multivariable analyses indicated minimal evidence that skeletal characteristics moderated the hypertrophic response to training. These findings do not support a meaningful role of pre-training bone characteristics in influencing the lean tissue mass adaptations to shorter-term resistance training.

physiology↗