A loss of voluntary muscle strength predisposes elders to a 4-fold increase in functional limitations and a 2-fold increase in mortality. For decades, the loss of strength in aging has been largely attributed to the loss of muscle mass. However, recent findings clearly demonstrate that muscle size plays a relatively minor role, and our preliminary data suggests that weak elders activate a substantially smaller proportion of their total muscle during a maximal strength task in comparison to their stronger age-matched counterparts. Despite the significance of maintaining physical strength in aging, virtually all of the research on this topic has focused exclusively on maintaining muscle mass, and little is known regarding the neural mechanisms of weakness. We hypothesize that dynapenic elders have a decreased ability to voluntarily (neurologically) activate skeletal muscle maximally due to increased intracortical inhibition. To test our hypothesis we will conduct a case-control study on dynapenic (i.e., weak) and non-dynapenic elders (n=50/group;>65 yrs). Additionally, the dynapenic individuals will be randomly assigned to one of two interventions (motor imagery (MI) or unilateral resistance exercise (URE) training) to provide an experimental manipulation to increase strength and VA, which will permit us to better elucidate physiological mechanisms. This project will address three specific aims. The first is to determine whether dynapenic elders exhibit differences in knee extensor voluntary activation (VA) in comparison to non-dynapenic elders. The second is to determine whether dynapenic elders exhibit differences in intracortical excitability (assessed via paired-pulse transcranial magnetic stimulation) of the quadriceps femoris muscles in comparison to non-dynapenic elders, and to examine the association between measures of intracortical excitability and VA. The last is to determine the association between the changes in strength, VA, and intracortical excitability induced by motor imagery training and unilateral resistance exercise training in dynapenic individuals. MI of strong muscle contractions has been shown to enhance strength and VA. URE training has also been shown to enhance strength and VA in both the trained and untrained limbs. We will use these interventions as manipulations to enhance strength and VA. This will allow us to better elucidate the mechanistic role of intracortical excitability by examining the association/disassociation between the respective outcomes. While not part of the specific aims per se, we will obtain a number of additional outcomes to characterize the participants, serve as covariates, and use for secondary analyses (e.g., muscle size via MRI, muscle fatigue, white matter hyperintensity, physical activity, electrically-stimulated contractile properties, physical performance, trait and state measures related to exercise, etc.). The proposed work will provide evidence that weakness in the elderly is associated with impairments in VA and will provide insight on the neural mechanisms of this impairment. Collectively, this knowledge will guide the development of targeted strategies to ameliorate weakness and enhance physical function in seniors.
The proposed research is relevant to public health because it will advance the understanding of the physiological mechanisms of muscle weakness in older adults. Muscle weakness is a major risk factor for the development of physical disability in old age. As such, this application is highly relevant to NIH's mission of extending healthy living and reducing the burdens of physical disability in old age.
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|Consitt, L A; Clark, B C (2018) The Vicious Cycle of Myostatin Signaling in Sarcopenic Obesity: Myostatin Role in Skeletal Muscle Growth, Insulin Signaling and Implications for Clinical Trials. J Frailty Aging 7:21-27|
|Arnold, W David; Clark, Brian C (2017) Is sarcopenia driven by motor neuron/unit loss? An unresolved question. Muscle Nerve 55:930|
|Loucks, Anne B; Clark, Brian C; Bowman, Lyn (2017) Response to ""Clinical Evaluation of Bone Strength and Fracture Risk"". Curr Osteoporos Rep 15:396-397|
|Oki, Kentaro; Clark, Leatha A; Amano, Shinichi et al. (2017) Effect of Anodal Transcranial Direct Current Stimulation of the Motor Cortex on Elbow Flexor Muscle Strength in the Very Old. J Geriatr Phys Ther :|
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|Manini, Todd M; Clark, Brian C (2016) Letter to the editor: results from a Web-based survey to identify dynapenia screening tools and risk factors. J Cachexia Sarcopenia Muscle 7:499-500|
|Oki, Kentaro; Law, Timothy D; Loucks, Anne B et al. (2015) The effects of testosterone and insulin-like growth factor 1 on motor system form and function. Exp Gerontol 64:81-6|
|Clark, Brian C; Taylor, Janet L; Hong, S Lee et al. (2015) Weaker Seniors Exhibit Motor Cortex Hypoexcitability and Impairments in Voluntary Activation. J Gerontol A Biol Sci Med Sci 70:1112-9|
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