Fatigability of Lower Limb Muscle in Older Adults: Protective Effects of Strength Training Exercise in Old Men and Women

Not Applicable

Recruiting

• Conditions: Aging
• Interventions: Other: Exercise

• Registration Number: NCT03888040
• Lead Sponsor: Marquette University

Brief Summary

The proposed studies will assess 1) the mechanisms for the age-related increase in fatigability during dynamic exercise (Aims 1 and 2) and 2) the effectiveness of high-velocity resistance training coupled with blood flow restriction (BFR) in improving muscle power output and fatigability in older adults (Aim 3). The first two aims are cross-sectional studies comparing young (18-35 years old) and older adults (≥60 yrs old) to test our central hypothesis that the greater accumulation of metabolites and increase in fatigability in older adults is due to either age-related impairments in skeletal muscle bioenergetics (Aim 1) and/or vascular dysfunction (Aim 2). These two aims will integrate techniques to assess whole-muscle bioenergetics (31P-MRS) and in vivo vascular function (near infrared spectroscopy; NIRS and doppler ultrasonography) with in vitro assessment of single fiber bioenergetics (epifluorescence microscopy) and vasoreactivity of isolated skeletal muscle arterioles (video microscopy). We will then determine whether bioenergetics, vascular function and fatigability are altered in older men and women in response to 8 weeks of resistance exercise training of the lower limb both with and without blood flow restriction (Aim 3).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-14
• Study First Submitted QC: 2019-03-21
• Study First Posted: 2019-03-25
• Study Start: 2020-09-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-25
• Last Update Posted: 2024-03-27
• Primary Completion: 2025-03-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• men and women aged 18-40 years and >60 years

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Exclusion Criteria

• body mass index ≥40 kg/m2;
• type 1 or type 2 diabetes;
• uncontrolled hypertension;
• active cancer, cancer in remission, or having received treatment for any form of cancer in the previous five years;
• coronary artery disease;
• cardiovascular disease (e.g., PAD, PVD);
• abnormal and untreated thyroid function;
• chronic and/or regular nonsteroidal anti-inflammatory drugs (NSAID) consumption,
• tobacco use (includes smoking);
• any condition that presents a limitation to exercise (e.g., severe arthritis, COPD, neuromuscular disorder, moderate or severe cognitive impairment, Alzheimer's Disease, severe untreated sleep apnea).
• women who are pregnant or likely to be pregnant.
• Subjects will be excluded if they have joint pain in the exercising leg or arm. Medication use. Medications currently taken or in the previous year and known to influence muscle mass (e.g., glucocorticoids, testosterone) and cortical and neuromuscular excitability will be exclusionary, while medications that may be prevalent among older adults (e.g., statins) will be accounted for with a covariate statistical model.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Resistance Training Only	Exercise	This leg will then perform low-load resistance training (30% of 1-RM) including 3 sets of 15 knee extensions performed as fast as possible while seated upright in a knee extension weight machine. Sets will be interspersed with 30 seconds rest. This leg will always perform the training without blood flow restriction.
Blood Flow Restriction Training	Exercise	This leg will then perform low-load resistance training (30% of 1-RM) including 3 sets of 15 knee extensions performed as fast as possible while seated upright in a knee extension weight machine. Sets will be interspersed with 30 seconds rest. This leg will always perform the training with blood flow restriction.

Primary Outcome Measures

Name	Time	Method
Change in muscle volume of the quadricep muscles form baseline to after 8 weeks training	Before and after completion of resistance training intervention of 8 weeks.	Magnetic resonance imaging (MRI) is used to detect the muscle volume.
Change in Fatigability of the knee extensor muscles from baseline to after 8 weeks training	One session before and then after 8 weeks of training	Fatigability will be quantified as the change in limb muscle power output from the start ot the end of a 4-minute dynamic fatiguing exercise.
Change in single muscle fiber function form baseline to after 8 weeks training	Before and after completion of resistance training intervention of 8 weeks.	Muscle Biopsies: An area of vastus lateralis will numbed by injection with local anesthetic. A small 1/4 inch incision will be made in the skin and a needle inserted briefly into the muscle to remove a piece of muscle about the size of a pencil eraser. The incision is pulled closed with a bandage and the area over the incision will be covered with an elastic pressure bandage. The whole muscle biopsy procedure will take a total of approximately 15 minutes, with the actual biopsy lasting only a few seconds. The biopsy samples will be stored for analyses and used to examine various aspects of skeletal muscle health.
Change in muscle metabolism during a fatiguing knee extensor exercise from baseline to after 8 weeks resistance training	Before and 2-days after completion of resistance training intervention of 8 weeks.	Phosphorus magnetic resonance spectroscopy (P-MRS) is used to noninvasively measure or calculate a measure of muscle metabolism using intracellular pH in the quadriceps.
Change in vascular function via flow-mediated dilation of the femoral artery from baseline to after 8 weeks of training	One session before and one after 8 weeks of training	Macrovascular endothelial function of the leg with doppler ultrasonography by measuring the blood flow response (velocity and arterial diameter) of the femoral artery after 5 minutes of lower limb occlusion
Change in myofibrillar-ATPase efficiency from baseline to after 8 weeks of training	One session before and after 8 weeks of training	Myofibrillar ATPase efficiency will be measured during shortening contractions in single fibers isolated from biopsies of the vastus lateralis via epifluorescence microscopy
Change in Oxygenation of the muscle between baseline to after 8 weeks of training	One session before and after 8 weeks of training	Tissue oxygenation levels of the knee extensors muscles will be measured during the 4-minute dynamic fatiguing exercise with near infrared spectroscopy
Change in arteriole Vasodilation from baseline to after 8 weeks of training	One session before and after 8 weeks of training	Acetylcholine-induced vasodilation will be measured in arterioles excised from muscle biopsies of the vastus lateralis via video microscopy

Secondary Outcome Measures

Name	Time	Method
Strength	One session before and after 8 weeks of training	1. The maximal load that can be lifted with each participant's knee extensor muscles will be assessed to determine the one repetition maximal strength (1-RM).; 2. Strength will also be assessed by measuring the isometric MVC of the knee extensors.

Trial Locations

Locations (1)

Marquette University; 🇺🇸 Milwaukee, Wisconsin, United States