# Muscle Fatigue and its Impact on Mobility Function in Aging

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $518,073

## Abstract

PROJECT SUMMARY
Compared with young adults, people over the age of 65 years experience greater muscle fatigue at high
contraction velocities, such as those that occur during walking. Although fatigue, or the acute decrease in
maximal force or power, is a fundamental characteristic of skeletal muscle, the pathway from impaired
cellular energetics, contractile function and fatigue to age-related changes in mobility function remains
unknown. Mobility reduction in older adults carries an increased risk for morbidities and a poor quality of life,
which in turn creates tremendous personal and societal burdens. Mobility dysfunction in older adults is
associated with decrements in knee extensor muscle (KE) function. Notably, the KE of older adults exhibit a
deficit in oxidative energy production in vivo, as well as greater fatigue compared with young adults. A novel
means to address the clinical problem of KE fatigue and its impact on mobility in aging is to determine the
fundamental molecular and cellular deficits that contribute to greater fatigue in older adults, and how these
fatigue mechanisms lead to mobility dysfunction. The overall goal of our research is to provide this new
knowledge and mitigate decreased mobility in our aging population. Our central hypothesis is that the KE of
older adults, particularly those with mobility dysfunction, will have deficits of in vivo mitochondrial energy
production that exacerbate impaired contractile function and result in greater fatigue during energetically-
demanding work, including walking. To test this hypothesis, data will be gathered before and after fatiguing
high-velocity contractions in 30 healthy young (30-40 yr), 30 healthy older (70-80) and 30 older (70-80)
adults with mobility impairment. All groups will be relatively sedentary, which will be verified quantitatively
using accelerometry. We will use an integrated and translational approach to build from the molecular to the
behavioral, by measuring: intracellular energetics using non-invasive magnetic resonance (MR) spectrosopy;
muscle morphology by MR imaging; single muscle fiber calcium sensitivity and myosin-actin cross-bridge
kinetics during fatigue conditions; force-velocity relationships of single fibers and intact muscle; lower
extremity joint mechanics, the energy cost of walking, perceived exertion and mobility tasks (chair rises,
balance) before and after fatigue. We will determine the role of deficits in both energy production (Aim 1) and
contractile function (Aim 2) in the greater muscle fatigue of older adults, as well as the impact of fatigue on gait
mechanics, the energy cost of transport, and mobility (Aim 3). Potential sex-based differences will be
evaluated in each Aim. The problem to be addressed- the causes of greater fatigue and how it impacts mobility
in older adults- tackles stated goals of the NIH and NIA. Our success will have a significant, positive impact by
bridging an existing knowledge gap that currently limits our ab...

## Key facts

- **NIH application ID:** 10198744
- **Project number:** 5R01AG058607-03
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** JANE A KENT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $518,073
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198744

## Citation

> US National Institutes of Health, RePORTER application 10198744, Muscle Fatigue and its Impact on Mobility Function in Aging (5R01AG058607-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10198744. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*