Understanding n-3 Pufa: A Dosing Approach To Study Incorporation, Washout, And Molecular Mechanisms In Ageing

Abstract

The global population is getting older. Ageing is associated with a loss in skeletal muscle mass (SMM) and strength. SMM, accounting for ~40% of total body weight, is crucial for health. Reductions in SMM result in increased frailty and decrease quality of life. Therefore, it is essential to elucidate new strategies that can counteract the loss of SMM with age. Accumulating evidence has demonstrated that omega-3 polyunsaturated fatty acids (n-3 PUFA) can positively regulate skeletal muscle health via incorporation into phospholipid membranes of skeletal muscle. However, the relationship between dietary intake of n-3 PUFA and its incorporation into phospholipid membranes, as well as its impact on SMM regulation, remains unclear. Additionally, the washout rates after stopping supplementation have not been determined. Hence, the overall aim of this thesis is to gain insight into the incorporation, washout, and underlying mechanisms of n-3 PUFA following different doses in young and older adults, with a focus on muscle and ageing. Chapter 1 provides a comprehensive background to place the thesis in context, addresses gaps in the literature, and provides the reader with the aims and objectives of this thesis. Chapter 2 assesses the incorporation and washout of EPA and DHA, administered in a 3:2 ratio, over time at low and high concentrations in cell lysates and phospholipid membranes of C2C12 myotubes, with measurements of muscle protein synthesis and associated signalling pathways. Chapter 3 continues with a human trial investigating incorporation and washout of n-3 PUFA in erythrocytes, skeletal muscle phospholipid membranes, and adipose tissue, comparing two different dosing strategies in young and older adults. Finally, Chapter 4 aims to identify global changes in skeletal muscle transcriptome in response to n-3 PUFA supplementation in young and older adults. Chapter 5 discusses findings of this thesis in a broader context and addresses future directions. Overall, the outcomes from this thesis contribute to the body of literature concerning n-3 PUFA supplementation, incorporation, and washout while also aiming to elucidate some of the underlying mechanisms.