Dr Jason Tallis

CASE: Polyphenols as Therapeutic Agents for Skeletal Muscle Health: Implications in Muscle Pathology

University of Registration: Coventry University

Non-academic partner: Mr Daniel Herman (Bio-Synergy)

Secondary Supervisor(s): Dr Sam Oxford

Project Outline

Skeletal muscle (SkM) health is fundamental to whole-body health, exhibiting a bidirectional relationship with organ function, biological tissues, and systemic physiological regulation. Importantly, impaired SkM function is recognised as an independent risk factor for disease and all-cause mortality. As such, investigating the efficacy of non-pharmacological interventions for the prevention and treatment of SkM pathology holds significant potential for improving human health. Increasing age, obesity, and diabetes mellitus represent major population-level health threats that are both attributable to and exacerbated by skeletal muscle pathology. While the pathological SkM phenotype is complex and muscle-specific, mechanistically impaired SkM health has been attributed to reduced myogenesis, AMP-activated protein kinase activity, increased chronic low-grade inflammation, elevated intramuscular lipid accumulation, changes in fibre type composition and metabolic adaptations, degeneration in the process of excitation-contraction coupling, and altered function of cross-bridge machinery. Polyphenols are naturally occurring bioactive compounds found in plant-based foods, known for their antioxidant, anti-inflammatory, and metabolic regulatory properties. Polyphenols, particularly resveratrol, has been demonstrated to reduce markers of inflammation, activate AMPK, and increase SIRT1 and PGC-1α protein levels, leading to SkM mitochondrial biogenesis, enhanced mitochondrial function, and reduced intramyocellular lipids, adipocyte size and whole-body adiposity. Specifically, our recent in vitro work demonstrated that dietary resveratrol was able to prevent obesity-induced reductions in SkM function. A growing body of mechanistic evidence supports the translational potential of polyphenols in humans. While resveratrol has demonstrated promising anti-obesogenic effects, and there is strong mechanistic promise for enhanced SkM health, the evidence base remains limited and inconsistent. This PhD will address key knowledge gaps by examining the effects of resveratrol supplementation on SkM with a focus on dose-response relationships, intervention duration, and population-specific effects, but with a particular focus on reducing impaired muscle function with increasing age. Furthermore, this project will investigate the potential synergistic effects of resveratrol supplementation and resistance exercise on SkM health. Given resveratrol's established anti-inflammatory properties, the research will assess the potential of dietary supplementation to attenuate exercise-induced muscle damage resulting from interventions that emphasise eccentric muscle contractions, an approach increasingly recognised as a promising strategy for enhancing SkM function, particularly in individuals with metabolic syndrome.