Investigating the influence of exercise on myofibrillar protein synthesis and FOXO3-related molecular signalling in middle-aged women

Myofibrillar protein synthesis (MYOPS) is regulated by key molecular pathways, including MTOR, FOXO3, and ribosome biogenesis. While these pathways are well-characterised in animal models, their roles across varying physical activity levels in humans remain underexplored. Existing studies have largely focused on younger males, with limited data on middle-aged females. Through two experimental chapters this thesis investigated the impact of physical activity, particularly resistance training, on MYOPS and its regulatory pathways in human skeletal muscle. The first chapter examined how varying physical activity levels influence MYOPS and associated gene expression in young adults. To address the gap in middle-aged female populations, the second study evaluated the effects of a 12-week elastic band resistance training programme on lean mass and its underlying mechanisms of MYOPS and gene signalling through deuterium oxide labelling and qPCR, respectively. Results revealed an inverse relationship between FOXO3 activity and MYOPS across activity levels. Although resistance training improved hip abduction (+18.5%), hip flexion (+20.2%), and lean mass (~0.7 kg; ~1.7%), it did not increase post-training MYOPS. Molecular analyses showed selective upregulation of a single ribosome biogenesis gene (NCL), with no significant changes in MTOR or FOXO3 transcripts, aligning with the unchanged MYOPS response. These findings provide novel insight into FOXO3 as a negative regulator of MYOPS and offer the first evidence that muscle adaptations in middle-aged females may occur independently of increased MYOPS. This work contributes to a more nuanced understanding of muscle remodelling in ageing females and highlights the potential role of muscle protein breakdown in mediating resistance training adaptations.<p></p>