The Effects of Ageing and Obesity on the Contractile Properties of Isolated Locomotory and Respiratory Skeletal Muscles

Abstract

Ageing is associated with a decline in skeletal muscle strength and power resulting in impaired in vivo locomotory and respiratory muscle function. It has been suggested that obesity in old age can exacerbate the reduction in skeletal muscle contractile function, though findings in older humans are equivocal. Ageing and obesity are associated with a significant decline in muscle quality in isolated skeletal muscles, though the capacity for producing and sustaining power, both concentrically and eccentrically, in isolated male and female locomotory and respiratory skeletal muscles is poorly understood. This is primarily due to the usage of contractility modes, such as isometric and isovelocity contractions, in isolated skeletal muscles poorly replicating in vivo contractile function. The work loop technique better replicates the in vivo contractile function of skeletal muscles by accounting for the power production during muscle shortening, and the passive forces during lengthening, thus providing a better model for examining isolated skeletal muscle contractile function. Using the work loop technique, this thesis examines the muscle-specific, sex-based differences in skeletal muscle ageing at multiple ages using males and females mouse skeletal muscles, and examines the effect of dietary-induced obesity in old age has on muscle function. The present work also outlines the differences in isometric force, concentric power across a range of contractile speeds and changes in eccentric power with increasing age. Between each study, absolute performance and performance normalised to muscle mass is calculated to provide an indication of changes in muscle quality. Finally, the ability of isolated muscles to withstand fatigue with age and obesity is determined. The results indicate that absolute concentric and eccentric power output and isometric force are well maintained with increasing age, with absolute power usually greater in males than females. When power output is normalised to muscle mass, there are few sex-based differences in the age-related decline in power output, though normalised performance in the oldest animals is worse for males than females. Furthermore, acute eccentric power output is well maintained with age, and older locomotor muscles are more fatigue resistant when fatigued eccentrically compared to young counterparts. Obesity in old age, however, does not further worsen locomotory performance normalised to muscle mass, nor fatigue resistance, but is deleterious to diaphragmatic power. Increasing age results in greater body mass, with larger muscles of poorer quality. When considered in vivo, larger muscles of poorer quality contribute to an already elevated body mass and consequently may impair acute and sustained locomotor and respiratory function in vivo, where muscles of poorer quality are required to work against a greater bodily inertia. Although there is some evidence that obesity may accelerate the age-related decline in function, this was not uniform across all of the muscles assessed. As such, the functional impairments seen in the sarcopenic-obese populations is largely the result of weakened muscles moving and controlling a greater muscle mass.

Date of Award	4 Apr 2019
Original language	English
Awarding Institution	Coventry University
Supervisor	Jason Tallis (Supervisor), Rob S James (Supervisor) & Val M Cox (Supervisor)