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 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.

Muscle paralysis and myosin loss in a patient with cancer cachexia.

Cancer cachexia has a significant negative effect on quality of life, survival and the response to treatment. Recent in vitro and experimental animal studies have shown that myosin may be the primary target of the muscle wasting associated with cancer cachexia. In this study, we have extended these analyses to detailed studies of regulation of myofibrillar protein synthesis at the gene level, myofibrillar protein expression and regulation of muscle contraction at the muscle cell level in a 63-year old man with a newly diagnosed small cell lung cancer and a rapidly progressing lower extremity muscle wasting and paralysis. A significant preferential loss of the motor protein myosin together with a downregulation of protein synthesis at the transcriptional level was observed in the patient with cancer cachexia. This had a significant negative impact on muscle fiber size as well as maximum force normalized to muscle fiber cross-sectional area (specific tension).

The influence of ageing on the force-velocity-power characteristics of human elbow flexor muscles.

The purpose of this study was to quantify the effects of ageing on the maximal power (P(max)) of the elbow flexor muscles and to determine the impact of velocity on the loss of power in older people. Sixteen elderly subjects (7 men and 9 women, age range 61-78 years) and 17 young subjects (11 men and 6 women, age range 18-27 years) participated in this study. Maximal elbow flexions were performed against increasing inertia. The maximal force (F(max)), maximal shortening velocity (V(max)), P(max), dynamic constants (a, b and a/F(max)), optimal force (F(opt)), optimal velocity (V(opt)) and V(opt)/V(max) were determined from Hill's equation. Myoelectrical activity (EMG) of the biceps and triceps muscles was quantified as an root mean square (RMS) value. F(max), V(max), P(max), F(opt), and V(opt) were significantly lower in elderly than in young subjects (28, 31, 45, 24 and 28% lower, respectively; p<0.05), whereas a/F(max) and V(opt)/V(max) were not different between the two age groups. In women, the greater decrease in P(max) appears to be more dependent on V(opt) than F(opt). In addition, V(max) decreased with age in women but not in men. The absence of significant differences between age groups in normalised RMS values indicates that P(max) and V(max) loss with increasing age could result more from changes in the properties of contractile element than from changes in muscular activity.