TY - JOUR T1 - Exercise induces myonuclear remodelling in humans independently of age JF - bioRxiv DO - 10.1101/2022.09.20.506578 SP - 2022.09.20.506578 AU - E. Battey AU - J.A Ross AU - A. Hoang AU - D.G.S. Wilson AU - Y. Levy AU - R.D. Pollock AU - M. Kalakoutis AU - J.N. Pugh AU - G.L. Close AU - G. M. Ellison-Hughes AU - N.R. Lazarus AU - T. Iskratsch AU - S.D.R. Harridge AU - J. Ochala AU - M.J. Stroud Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/09/21/2022.09.20.506578.abstract N2 - 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 training resulted in increased levels of Lamin A and increased myonuclear stiffness in mice. We conclude that exercise induces myonuclear remodelling, regardless of age, which contributes to the preservative effects of exercise on muscle function throughout the lifespan.Competing Interest StatementThe authors have declared no competing interest. ER -