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 endurance training status. Nuclear morphology and the distribution of nuclear envelope proteins important for nuclear architecture and mechanotransduction (SUN1) were studied in isolated human muscle fibres from individuals of different ages and endurance training statuses. So far, the data indicate that in humans, changes in myonuclear morphology occur in response to exercise regardless of age, indicated by a 6-10% reduction in myonuclear sphericity and 25-30% reduction in myonuclear aspect ratio in young and older exercise-trained individuals compared to inactive young and older counterparts (n = 6 per group, p < 0.05 one-way ANOVA). No differences in the distribution of SUN1 were revealed through super-resolution microscopy. Endurance training therefore appears to influence nuclear morphology in a manner unaffected by age; alterations to nuclear envelope proteins other than SUN1 may be involved in this process. Ongoing research is focused on whether these changes are recapitulated in mice and if the distribution of nuclear envelope proteins Lamin A and Nesprin-1 and muscle-specific cytoskeletal protein Desmin are altered with endurance training. Whether alterations to myonuclear mechanics influences gene transcription will also be assessed through cell microharpooning and RNA sequencing.