Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with nuclear lamina protein Lamin A regulating nuclear shape, nuclear mechanics, and ultimately gene expression. Defective Lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than untrained individuals. Complementary to this, exercise resulted in increased levels of Lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. Abstract figure legend Structural and mechanical properties of myonuclei in trained young and aged individuals. In skeletal muscle fibres from trained individuals, myonuclei are more spherical, have greater Lamin A and are stiffer compared to untrained counterparts. This may protect nuclei from damage when subjected to contractile forces during exercise, and permit effective transduction of these forces to regulate gene expression and signalling pathways (mechanotransduction). In skeletal muscle from untrained older individuals, myonuclei are more elongated, nuclear lamina levels are lower, and myonuclei are more deformable. This may increase susceptibility to myonuclear damage and defective mechanotransduction, contributing to declines in muscle mass and function. This article is protected by copyright. All rights reserved.