Maintaining mobility is fundamental to extending our healthspan. Reduced mobility may be driven by fatigability, a new metric that quantifies deterioration in performance and the accompanying increase in perceived effort. Muscle fatigue (decrease in maximal power with activity) in older adults, and to a greater degree in those with mobility impairments, could contribute to greater fatigability in aging through changes in muscle coordination, leading to altered gait mechanics and a higher metabolic cost of walking. Ourscientific premise for the proposed role of muscle fatigue is built on robust evidence that older adults have greater muscle fatigue in major locomotor muscles during low-load, high-velocity maximal concentric contractions; and greater knee extensor muscle fatigue in response to a treadmill walk than younger adults. However, evidence is lacking for how muscle fatigue compounds age- or impairment-related muscle weakness to alter gait neuromechanics, and the connections to cost of walking and fatigability. Our overall goal is to generate a new framework for understanding fatigability by quantifying the neuromechanical effects and energetic consequences of muscle fatigue on gait, so that efficacious interventions to prevent or reverse fatigability can be pursued. Our central hypothesis is that muscle fatigue contributes to fatigability by exacerbating age-related changes in gait mechanics and variability (Aim 1) through changes in the control and coordination of gait (Aim 2), such that with muscle fatigue greater energy is required for walking in older adults (Aim 3). To test this hypothesis, data will be gathered for 4 groups of 15 men and 15 women each: sedentary young (30-40 yr) and older (70-80) healthy adults, mobility-impaired older adults (70-80), and active older adults (70-80 yr). This combination of groups will allow us to evaluate the independent effects of age, physical activity and mobility impairment, and test for sex effects. All groups, except the active older, will be relatively sedentary, similar to the general US population. We will use our new, physiologically- and clinically-relevant 30 minute treadmill walk to cause lower-extremity muscle fatigue and quantify the response with measures of gait mechanics and variability, electromyography, and energy cost of walking. Computer simulations of walking based on models representing the 4 groups will help provide a mechanistic understanding of the muscular basis for the gait adaptations and consequences for whole body energetics. The modeling and experimental approaches are tightly integrated to identify how individual muscles contribute to fatigue-induced altered gait mechanics and increased energy cost of walking with age and impairment (Aim 2 & 3). The problem to be addressed- fatigability and its impact on mobility in aging- tackles stated goals of the NIH and NIA. Project success will have a significant impact by bridging an existing knowledge gap from muscle weakness and fatigue to the fatigability that currently prevents many older adults from achieving an optimal healthspan.
The proposed research will address a critical public health problem, fatigability- a predictor of future mobility problems in aging, by determining biomechanical and energetic consequences of greater muscle fatigue in older adults. Our innovative, translational approach, which combines state-of-the-art experimental and computational approaches from tissue to behavioral levels, will provide the new information necessary to bridge an existing knowledge gap and thus enable translation of basic science to public health. Our mechanistic outcomes of fatigability will identify promising targets for intervention to mitigate or prevent fatigability and related mobility decline in our aging population, as such, this project is highly relevant to the missions of NIH and NIA.
