Exercise and nutritional strategies for human muscle metabolic regulation with ageing and inactivity

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Marshall, Ryan Neil (2023). Exercise and nutritional strategies for human muscle metabolic regulation with ageing and inactivity. University of Birmingham. Ph.D.

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Abstract

Age-related skeletal muscle wasting, or "sarcopenia", negatively impacts physical function and health. The mechanisms relating to sarcopenia are complex and unclear but are thought to be underpinned by a blunted response of skeletal muscle to anabolic stimuli and the accumulation of dysfunctional mitochondria. Moreover, these issues may be further worsened with brief periods of disuse and inactivity. Therefore, resistance exercise (RE) and nutritional strategies are of paramount importance to offset the further decline. Accordingly, Chapter 2 explored the molecular consequences of a brief five-day period of bed rest in older adults. Moreover, I explored how RE prehabilitation prior to bed rest may potentially offset declines in mitochondrial protein expression. However, I showed that neither 5-days of bed rest or prior RE prehabilitation affects markers of mitochondrial content, function, or fission-fusion dynamics. Chapter 3 determined the effect of lifelong exercise on skeletal muscle mitochondrial content and quality control in a cohort of 'master athletes' and sedentary older adults in a rested and 1 hr post-RE. I observed significantly elevated abundance in a range of mitochondrial proteins in MA compared to untrained older adults, suggesting greater mitochondrial health and function. However, acute RE was unable to alter mitochondrial protein expression or phosphorylation status involved in biosynthesis and fission-fusion dynamics. Chapter 4 investigated the acute neuromuscular response to a pragmatic RE mode, elastic band exercise (EB-RE), and how this compared to traditional machine RE (MN-RE) in younger and older adults. I observed no significant differences in EMG activity between EB-RE and MN-RE in either group. Thereby providing preliminary evidence for EB-RE as a potential RE stimulus in the absence of MN-RE equipment. Following this, Chapter 5 assessed the integrated muscle protein synthetic (iMyoPS) response with an oral D2O tracer methodology in younger and older adults. I observed a robust increase in iMyoPS following EB-RE in both groups. However, iMyoPS was blunted in older adults, independent of similarities in acute mTORC1 signalling. Chapter 6 provides a study protocol for a currently ongoing randomised, double-blind, placebo-control study investigating the potential protective effects of a high-dose, leucine-enriched essential amino acids (Leu-EAA) at preventing muscle atrophy, muscle proteostatic imbalance, and mitochondrial dysfunction following period of reduced activity, in a cohort of healthy older adults. In conclusion, this thesis enhanced our understanding of the mechanisms underpinning ageing and sarcopenia by investigating the effects of disuse and inactivity and their effects on whole-body and muscle-specific metabolism/signalling, overall demonstrating the protective role of acute and lifelong exercise, as well as nutritional support on musculoskeletal health.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):