The overall goal is to determine the magnitude and mechanisms of age-related changes in muscle fatigue (decrease in maximal force-generating capacity, MVC). Clarification of the influence of age on fatigue has important implications for health and the maintenance of independent living in aging. We will study the ankle dorsiflexor and knee extensor muscles of healthy young (20-35 yrs) and older (70-85 yrs) adults. Muscle Metabolism and Perfusion (Years 1-2). ATP for muscular work is synthesized by 3 pathways: the creatine kinase (CK) reaction, oxidative phosphorylation and anaerobic glycolysis. Inadequate ATP supply can result in fatigue.
Specific Aim I, Metabolic Capacity: To determine whether older muscle exhibits a decreased capacity to produce ATP. we will use magnetic resonance spectroscopy (MRS) to measure the capacities of these pathways. Hypotheses IA-C: Dorsiflexors will show A) similar CK kinetics, B) similar oxidative capacities, C) lower peak glycolytic rates in older adults. Hypotheses ID-F: Knee extensors will show D) similar CK kinetics, E) lower oxidative capacity in older, F) lower peak glycolytic rates in older adults.
Specific Aim 2, Muscle Perfusion: To examine the relationships between dorsiflexor muscle strength, contraction intensity and blood flow occlusion, we will measure the reactive hyperemia of young and older adults using functional MR imaging during a series of isometric contractions. Hypothesis 2A: There will be no difference by age in the force (N) at the intersection of the bilinear relationship between the hyperemic response and absolute force. Hypothesis 2B: The intersection of the relationship between the hyperemic response and relative force will occur at a higher percentage of MVC. Muscle Fatigue (Years 3-5). Both muscle group and type of contraction may alter the outcome in studies of muscle fatigue in aging.
Specific Aim 3, Muscle Group Specificity in Fatigue: To determine the impact of muscle and contraction type on the extent and mechanisms of fatigue in aging, we will compare dorsiflexor and knee extensor fatigue during maximal intermittent and maximal sustained isometric contractions We will measure activation, contractile function, metabolism and hyperemia. Hypothesis 3A: During the intermittent protocols, older will fatigue less and show less decrease in muscle pH. Hypothesis 3B: During the sustained protocols, older and young will fatigue similarly and have the same metabolic response. Hypothesis 3C: The magnitude of the age-based increase in fatigue resistance during the intermittent protocol will be greater in the dorsiflexors compared to the knee extensors.
Specific Aim 4, Task Spec Specificity in Fatigue (Exploratory): In Years 4 and 5, we will 1) measure fatigue, activation and contractile function in the 2 muscle groups using isovelocity contractions, 2) use the Hill Model to investigate the role of contractile and series elastic properties in fatigue, and 3) develop methods to perform dynamic fatigue studies in the MRS system.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-GRM (01))
Program Officer
Dutta, Chhanda
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Massachusetts Amherst
Other Health Professions
Schools of Public Health
United States
Zip Code
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

Showing the most recent 10 out of 25 publications