# Fatigability of Limb Muscle in Older Adults: Protective Effects of Exercise

> **NIH NIH R01** · MARQUETTE UNIVERSITY · 2021 · $618,678

## Abstract

ABSTRACT
 Losses in limb muscle mass and increased fatigability compromise the ability of older adults (≥65 yrs) to
generate the power necessary to maintain mobility and perform daily activities. Recently, we showed that the
age-related increase in fatigability during dynamic contractions is due to a greater accumulation of metabolites,
hydrogen (H+), inorganic phosphate (Pi) and diprotonated phosphate (H2PO4-), eliciting greater disruptions in
contractile function within the muscle. However, the mechanisms for the greater metabolite accumulation are
unknown. Our central hypothesis is that the greater accumulation of metabolites and increased fatigability are
due to age-related impairments in skeletal muscle bioenergetics and/or vascular function. To test this hypothesis,
we will use cutting-edge techniques to assess whole-muscle and single fiber bioenergetics and macro- and
micro-vascular function. Additionally, we will study the effectiveness of a novel exercise-training intervention in
older men and women aimed at improving contractile economy, vascular function, muscle power and fatigability.
Aim 1 will determine the bioenergetic basis for the age-related increase in fatigability in the whole quadriceps
muscle and in single fibers isolated from muscle biopsies of the vastus lateralis. Quadriceps muscle contractile
economy and the accumulation of intracellular metabolites (H+, Pi, H2PO4-) will be assessed with 31phosphorus
nuclear magnetic resonance spectroscopy (31P-MRS) during dynamic knee extension exercise. Myofibrillar and
sarcoplasmic reticulum-Ca2+ ATPase activity and fiber efficiency will also be measured during shortening
contractions of single fibers using epifluorescence microscopy. We hypothesize that older adults will have a
lower whole muscle and single fiber contractile economy compared with young adults. Aim 2 will assess whether
dysfunction of the macro- and micro-vasculature is a mechanism for the increased fatigability with aging. During
dynamic knee extension exercise, femoral artery blood flow will be quantified via Doppler ultrasonography and
tissue oxygenation measured with near infrared spectroscopy (NIRS). Microvascular function will be assessed
in arterioles isolated from vastus lateralis biopsies using video microscopy. We hypothesize that older adults will
have reduced femoral artery blood flow and greater reductions in quadriceps muscle oxygenation compared with
young adults, in part, due to a blunted vasoreactivity of arterioles. Aim 3 will determine the effectiveness of a
high-velocity resistance exercise training coupled with blood flow restriction to improve fatigability in older men
and women. Older adults will perform 8 weeks of dynamic unilateral resistance exercise, where one leg is
exercised with freely perfused conditions and the other with blood flow restriction. We hypothesize that
fatigability, bioenergetics and vascular function will improve in the exercise training leg with blood flow restriction
and...

## Key facts

- **NIH application ID:** 10240716
- **Project number:** 5R01AG048262-07
- **Recipient organization:** MARQUETTE UNIVERSITY
- **Principal Investigator:** Robert H Fitts
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $618,678
- **Award type:** 5
- **Project period:** 2015-09-01 → 2025-04-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240716

## Citation

> US National Institutes of Health, RePORTER application 10240716, Fatigability of Limb Muscle in Older Adults: Protective Effects of Exercise (5R01AG048262-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10240716. Licensed CC0.

---

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