The ability of human skeletal muscle to perform work over a period of time is critical to the maintenance of health and competent physical functioning. In old age, there are profound changes that occur in the neuromuscular system, many of which are exacerbated by disuse. In this project we will continue pursuit of our long-term goal of elucidating the mechanisms and impact of skeletal muscle fatigue in aging humans by integrating measures of neural, contractile and metabolic function to test novel hypotheses related to the ability of old muscle to produce energy and force. At the same time, we will provide new information about fatigue (defined as the fall of maximal force-generating capacity) in older adults with early signs of impaired physical function.
Our Specific Aims are to determine the effects of: 1) old age and physical impairment on the neural and muscular components of muscle metabolic economy, and 2) age and physical impairment on the mechanisms of muscle fatigue. To accomplish our goals, we will use an integrative approach in which we measure the neural signals to the muscle, the ability of the muscle to provide energy, and its capacity to maintain vigorous contractions. This unique set of studies will be conducted using state-of-the-art methodologies, including in-dwelling electrodes and non-invasive magnetic resonance spectroscopy and imaging. Using a cross-sectional design, we will compare the magnitude and mechanisms of muscle fatigue, while accounting for differences in physical activity level and physical functioning in our study subjects. Over the course of this 4-year project, we will study the ankle dorsiflexor muscles of young (aged 21-35 years) and older (65-80) healthy and mobility-impaired men and women. The dorsiflexors provide an excellent model for the planned studies, and they are particularly important to competent locomotion. This project will provide a unique body of knowledge about how neural and metabolic factors may mediate age-related changes in fatigue resistance in a range of older subjects. We will address the long-standing gap that exists in our understanding of how the neural, contractile and metabolic systems are integrated to regulate neuromuscular function in young and older adults, and how that integration may be disrupted with the decline in physical performance in the elderly. PULBIC

Public Health Relevance

The age-related changes in the neuromuscular system are profound. Despite the vital importance of the neuromuscular system to health and independence in old age, the interactions between and regulation of the neural, energetic and muscular factors that support competent physical functioning are not clear at this time. By addressing these key gaps in knowledge, we will respond to two important priorities in geriatric research: 1) we will determine the ability of both healthy and physically-impaired older adults to """"""""respond to the stressor"""""""" of muscular work, and 2) we will identify potential """"""""preventable aspects of frailty"""""""" relatively early in the impairment-disability-frailty cascade.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Dutta, Chhanda
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University of Massachusetts Amherst
Other Health Professions
Schools of Public Health
United States
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Callahan, Damien M; Umberger, Brian R; Kent, Jane A (2016) Mechanisms of in vivo muscle fatigue in humans: investigating age-related fatigue resistance with a computational model. J Physiol 594:3407-21
Christie, Anita D; Foulis, Stephen A; Kent, Jane A (2016) ATP cost of muscle contraction is associated with motor unit discharge rate in humans. Neurosci Lett 629:186-188
Christie, Anita D; Seery, Emily; Kent, Jane A (2016) Physical activity, sleep quality, and self-reported fatigue across the adult lifespan. Exp Gerontol 77:7-11
Christie, Anita D; Tonson, Anne; Larsen, Ryan G et al. (2014) Human skeletal muscle metabolic economy in vivo: effects of contraction intensity, age, and mobility impairment. Am J Physiol Regul Integr Comp Physiol 307:R1124-35
Tevald, Michael A; Foulis, Stephen A; Kent, Jane A (2014) Effect of age on in vivo oxidative capacity in two locomotory muscles of the leg. Age (Dordr) 36:9713
Larsen, Ryan G; Callahan, Damien M; Foulis, Stephen A et al. (2012) Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior. Appl Physiol Nutr Metab 37:88-99
Christie, Anita; Snook, Erin M; Kent-Braun, Jane A (2011) Systematic review and meta-analysis of skeletal muscle fatigue in old age. Med Sci Sports Exerc 43:568-77
Callahan, Damien M; Kent-Braun, Jane A (2011) Effect of old age on human skeletal muscle force-velocity and fatigue properties. J Appl Physiol 111:1345-52
Tevald, Michael A; Foulis, Stephen A; Lanza, Ian R et al. (2010) Lower energy cost of skeletal muscle contractions in older humans. Am J Physiol Regul Integr Comp Physiol 298:R729-39
Tevald, Michael A; Lanza, Ian R; Befroy, Douglas E et al. (2009) Intramyocellular oxygenation during ischemic muscle contractions in vivo. Eur J Appl Physiol 106:333-43

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