Age-related declines in cellular structure and function can be initiated or accelerated by physical inactivity. Ageing is associated with aberrant nuclear morphology, architecture and translation of forces to biochemical signals (mechanotransduction); this project focuses on whether, in skeletal muscle, these changes are influenced by physical activity status. Nuclear morphology and the distribution of nuclear envelope proteins important for nuclear architecture and mechanotransduction (SUN1 and LEM2) were studied in isolated human muscle fibres from individuals of different ages and physical activity statuses. So far, the data indicate that in humans, changes in myonuclear morphology occur in response to exercise regardless of age, indicated by a 25-30% reduction in myonuclear aspect ratio in young and older exercise-trained individuals compared to inactive young and older counterparts. No differences in the distribution of proteins SUN1 or LEM2 were revealed through super-resolution microscopy. Exercise therefore appears to influence nuclear morphology in a manner unaffected by age; alterations to nuclear envelope proteins other than SUN1 and LEM2 may be involved in this process. Future research will be focused on analysing myonuclear morphology in 3D, the distribution of nuclear envelope proteins Lamin A and Nesprin-1 and muscle-specific cytoskeletal protein Desmin. Whether alterations to myonuclear mechanics influence gene transcription will also be assessed through cell microharpooning and RNA sequencing.