Effect Of Aging On The Lateral Transmission Of Force In Skeletal Muscle
Aging of skeletal muscle, characterized by involuntary loss of muscle mass and strength during aging, has become one of extraordinary concerns for the increasing elderly population. The reduction of muscle strength is partially caused by decreased skeletal muscle cross-sectional area (CSA) with ageing; however, muscle force is lost to a greater extent than the loss of muscle mass, suggesting that other factors are involved. Changes in ATPase activity, metabolite levels, or myosin isoforms cannot fully explain the loss of specific force in aged muscles. These findings suggest that the force transmission pathway from myofibers to the tendon in aged muscles might be impaired, therefore, lead to the loss of skeletal muscle strength. The aim of this study is to characterize the effects of aging on force transmission in skeletal muscle and determine the underlying mechanisms. In current study, firstly, we studied the mechanism of lateral transmission of force in skeletal muscle by a finite element model of single muscle fiber. We found that most of the force generated in myofibers is transmitted near the end of the myofiber through shear stress to the surrounding ECM. Force transmitted to the end is affected by mechanical and geometrical properties of ECM. Secondly, effect of aging on lateral transmission was determined by isometric contractile tests on the extensor longus muscle with series of tenotomy and myotomy on young and old rats. Significant drop in force with myotomy was observed in old rats, indicating the impaired lateral transmission pathway with aging, which could be partly due to increased thickness of the ECM. Possible mechanisms of the age-related change in force transmission were further explored through combining the transmembrane proteins into finite element analysis. We found that force transmitted in the muscle is sensitive to the amount of proteins; more force could be transmitted in model with more transmembrane proteins. However, the force transmission is not sensitive to the stiffness of transmembrane proteins. The thesis was concluded by a discussion of study and possible future work.
Earls, Christopher J; Hernandez, Christopher J.
Ph. D., Mechanical Engineering
Doctor of Philosophy
dissertation or thesis