Skeletal Muscle Bioenergetics in Ageing and Chronic Disease: Insights from Longitudinal and Interventional Studies

Over the past century, global life expectancy has risen markedly. This has been accompanied by an increased prevalence of age-related disorders and functional decline. One of the key manifestations of ageing is the deterioration of skeletal muscle, characterized by losses in mass, strength, and power, as well as a decline in aerobic capacity. Mitochondria play a critical role in regulating aerobic capacity; however, the extent to which ageing directly affects these organelles remains debated, due to contrasting findings from cross-sectional studies and a paucity of longitudinal data. To address this gap, the first aim of my Ph.D was to investigate potential longitudinal changes in skeletal muscle oxidative metabolism associated with ageing. Exercise training represents a key intervention to counteract the detrimental effects of conditions such as disease, disuse, and ageing. Nevertheless, the optimal training strategy to simultaneously improve muscle mass, strength, and oxidative metabolism in older adults remains uncertain. To better understand these mechanisms, part of my work examined the effects of moderate eccentric resistance training on mitochondrial adaptations in ageing, Ageing increases the risk of cardiovascular diseases such as heart failure with reduced ejection fraction (HFrEF), a condition characterized by both cardiac dysfunction and skeletal muscle bioenergetic impairment. Myosin plays a central role in skeletal muscle bioenergetics, as it can exist in two distinct resting biochemical states that influence ATP turnover. Alterations in these states may contribute to inefficient energy utilization, disrupted fiber homeostasis, muscle wasting, and exercise intolerance. Building on this, we explored myosin dynamics as a potential biochemical target to optimize skeletal muscle energy efficiency in HFrEF. Finally, this thesis included a methodological study aimed at evaluating whether cryopreserved samples could reliably substitute fresh tissue in the assessment of mitochondrial function, given that the use of fresh samples for high-resolution respirometry analyses poses economic, temporal, and logistical challenges.