Myonuclear alterations associated with exercise are independent of age in humans

• Published in: The Journal of physiology
• Main Authors: Battey, E, Ross, J A, Hoang, A, Wilson, D G S, Han, Y, Levy, Y, Pollock, R D, Kalakoutis, M, Pugh, J N, Close, G L, Ellison-Hughes, G M, Lazarus, N R, Iskratsch, T, Harridge, S D R, Ochala, J, Stroud, M J
• Format: Journal Article
• Language: English
• Published: England 30.01.2023
• Subjects: nuclei; exercise; nuclear lamina; ageing; nuclear shape
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP284128

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 the 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 those from 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. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.