Ageing of human myofibres in the Vastus Lateralis muscle: A narrative review

Human skeletal muscle is a complex, dynamic tissue that changes profoundly with age. It comprises heterogenous cells including long, contractile, multinucleated myofibres, broadly classified into type I (slow-twitch/oxidative) fibres and type II (fast-twitch/glycolytic) fibres, as well as a variety of mononucleated cells (e.g., immune, satellite, and endothelial cells), and the extracellular matrix (ECM). Ageing as well as sarcopenia, a muscle condition characterised by progressive loss of muscle strength and mass observed mostly in older adults, appear to disproportionately affect type II fibres. In histomorphometric studies of ageing muscle this has been described as type II myofibres loss, fibre atrophy, and redistribution of fibre types, although some inconsistent findings exist. The precise mechanisms underlying this selective vulnerability remains elusive but are likely attributable to dysregulated nutrient sensing contributing to the deregulation of muscle protein synthesis and degradation cycle, and neuromuscular junction, satellite cells, ECM and mitochondrial dysfunction. This narrative review focuses on the Vastus Lateralis (VL) muscle-a major limb muscle involved in locomotion and one of the most extensively studied human skeletal muscles-and summarises key structural and phenotypic changes that occur with ageing at the organ, tissue, and cell levels, and their relevance to sarcopenia. We also briefly discuss external influences of these changes, highlight gaps in knowledge, and suggest future directions.