Muscle Fatigue, Gait Alterations and Increased Energy Cost of Walking in Aging

PROJECT SUMMARY
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.

Grant Number: 5R01AG068102-05
NIH Institute/Center: NIH
Principal Investigator: Katherine Boyer