University of Vermont

College of Medicine

Toth Laboratory



Skeletal muscle size and function are progressively lost with age, a process that has been termed sarcopenia. The mechanisms underlying these changes, however, have not been clearly defined. Work from our laboratory has sought to determine the effects of aging on skeletal muscle protein metabolism, with a specific focus on myosin protein expression (Toth et al. 2005, 2006). These results confirmed earlier studies that had shown diminished skeletal muscle protein synthesis with age and advanced this work to suggest that diminished rates of protein turnover may be related to elevated inflammatory tone (Toth et al. 2005). Studies in animal models have buttressed this notion by showing that medications which diminish chronic inflammation may counteract sarcopenia (Rieu et al. 2009). Translation of these studies to humans to confirm the involvement of inflammation in the loss of skeletal muscle size and function, however, awaits further study.

We have been collaborating with colleagues in the Department of Molecular Physiology and Biophysics (Dr. Mark Miller) to evaluate the effects of aging on skeletal muscle size, structure and function. Healthy young and elderly individuals matched for sex and weight-bearing activity were compared for skeletal muscle structure and function at the whole muscle, cellular and molecular levels. After adjusting for muscle size, older adults had similar knee extensor isometric torque values compared to young, but had lower isokinetic power, most notably in females. At the single fiber and molecular levels, aging was associated with increased isometric tension, slowed myosin-actin cross-bridge kinetics (longer myosin attachment times and reduced rates of myosin force production), greater myofilament lattice stiffness and reduced phosphorylation of the fast myosin regulatory light chain; however, the age effect was driven primarily by females. Functional alterations at the molecular and cellular level were related to diminished function at the whole muscle and body level. These results suggest that age-related alterations in the myosin molecule contribute to skeletal muscle dysfunction and physical disability, and that this effect is stronger in females. This sex dimorphism may partially explain the greater rates of physical disability in older women. A preliminary report of these data has recently been published (Miller and Toth, 2013).

Last modified December 18 2013 02:38 PM