Effects of Aging on Proteolysis Signaling in Skeletal Muscles Following Electrically Stimulated Contractions

  • Chen, Chiao-Nan Joyce (PI)
  • Chang, Ya-Ju (CoPI)
  • Chen, Hsin-Yung (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Skeletal muscles, especially type II muscle fibers, become smaller and weaker with aging, which has a deleterious effect on the independence and quality of life of the elderly. Neuromuscular electrical stimulation (electrical stimulation), a modality for the increase of muscle mass and muscle strength, is a potential adjunct tool to prevent or rehabilitate muscle atrophy for the elderly since type II muscle fibers are more easily activated in electrical stimulation compared to that in voluntary muscle contractions. Nevertheless, electrically stimulated muscles are found to have greater inflammation and oxidative stress, which are two factors that trigger protein degradation (proteolysis) in skeletal muscles. In addition, scientific evidence of the influence of aging on proteolysis of muscles following electrically stimulated contractions is lacking. Our overall hypothesis is that electrically stimulated contractions cause more stress in aging muscles, which consequently results in greater protein degradation in muscles from old animals compared to that in muscles from adult animals. This hypothesis is based on previous studies, which indicated that aging muscles have higher baseline levels of inflammation and oxidative stress, impairment in defense systems to stimuli, and greater oxidative stress after muscle contractions. There are three specific aims in this three-year proposal: Aim1. To determine the effects of aging on inflammation and oxidative stress in skeletal muscles following electrically stimulated contractions. Aim 2. To determine the effects of aging on ubiquitin/proteasome proteolysis in skeletal muscles following electrically stimulated contractions. Aim 3. To determine the effects of aging on calpains, caspases, and autophagy/lysosome proteolysis pathways in skeletal muscles following electrically stimulated contractions. In order to test systematically whether aging muscles have greater stress and protein degradation following electrically stimulated contractions compared to that in adult muscles, we propose to conduct a two-factor mixed experimental study where one factor is age and the other factor is electrically stimulated muscle contractions. Sprague-Dawley rats at three different ages (12, 21 and 24 month-old) will be used representing the critical ages that show significant changes of muscle functions. Electrical stimulation will be performed on the sciatic nerve (anesthetized rats) with a protocol that has been shown to induce muscle hypertrophy of rats. The contralateral, non-stimulated, muscles will be used as control. Tibialis anterior muscles from stimulated and contralateral control hindlimbs will be removed immediately after electrically stimulated contractions. Markers of inflammation and oxidative stress, and the expressions of the key proteins and genes in the proteolysis pathways will be determined. Techniques including Western blot, enzyme assays, real time quantitative PCR will be used to collect data. The data will be analyzed statistically using two way ANOVA and the Tukey-Kramer Multiple Comparison Test. Relevance: Results of the proposed study will not only increase the knowledge in the field of muscle biology and rehabilitation but also provide the foundation for future studies that determine the optimal use of electrical stimulation for the elderly.

Project IDs

Project ID:PC10107-0294
External Project ID:NSC101-2314-B182-006-MY3
StatusFinished
Effective start/end date01/08/1231/07/13

Keywords

  • muscle
  • aging
  • electrical stimulation
  • protein degradation

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