Author(s): EDMONDSON, J., J A. EDMONDSON, C A. STEAD, M R. VIGGARS, H SUTHERLAND, J G. BURNISTON AND J C. JARVIS, Institution: LIVERPOOL JOHN MOORES UNIVERSITY, Country: UNITED KINGDOM, Abstract-ID: 2414

INTRODUCTION:
Resistance exercise is a primary intervention shown to maintain muscle mass during ageing, yet older adults show attenuated hypertrophic responses. Anabolic resistance contributes to sarcopenia, affecting 10–27% of older adults (Petermann‐Rocha et al., 2022). While previous studies have examined acute transcriptional responses to resistance exercise, how the transcriptome adapts over repeated training bouts, and whether this differs with age, remains poorly understood.
METHODS:
Twelve young (6-month) and fifteen aged (22–28-month) rats underwent unilateral programmed resistance training of the tibialis anterior, unstimulated contralateral muscle served as control. Muscles were harvested after 2, 10, 20, and 30 days of daily training with 5 sets of 10 loaded contractions. RNA-sequencing (Illumina NovaSeq) was analysed using limma-voom for differential expression and gene set enrichment analysis (GSEA) for pathway-level responses. sPLS-DA identified a 200-gene signature that was distinct in young and aged responses and in an independent ageing dataset (Shavlakadze et al., 2023).
RESULTS:
Aged muscle showed attenuated hypertrophy compared to young (Day 30: 13% vs 21% muscle mass increase; age p < 0.001, age×stim p=0.016). Both ages mounted robust transcriptional responses with similar numbers of differentially expressed genes, highly correlated between ages (r=0.76 at Day 2, declining to r=0.62 by Day 30). However, pathway-level analysis revealed progressive divergence. Young muscle showed reduced enrichment of oxidative phosphorylation gene expression while upregulating transcription of MYC targets, E2F targets, and ribosome biogenesis pathways. Aged muscle upregulates oxidative metabolism gene expression and showed progressive loss of growth-related pathway enrichment. This divergence was most pronounced at Days 10–20, where young muscle showed coordinated upregulation related to ribosome biogenesis and cell proliferation pathways while aged muscle prioritised metabolic gene expression.
CONCLUSION:
Young and aged muscle mount a similar acute transcriptional response to resistance training but progressively diverge in pathway-level execution. Young muscle sustains ribosome biogenesis and cell proliferation gene expression while suppressing oxidative metabolism genes. Aged muscle fails to sustain this shift, maintaining energy metabolism gene expression at the expense of growth-related programmes. These findings suggest that age-related anabolic resistance may arise not from a failure to respond to loading, but from an inability to sustain growth-oriented programmes over repeated bouts, and that interventions targeting metabolic capacity alongside resistance training may help restore the adaptive response in older adults.