Skeletal Muscle Mitochondria in Ageing

NCT06539078 | Recruiting DMC

• 1 other identifier: 2023.0746
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Healthy ageing is associated with the loss of muscle mass and physical function. As a result, older people are limited in their independence. The aging of muscles typically begins around the age of 30. From this age onward, muscle strength, muscle mass, and the maximum oxygen uptake of muscles decrease. The reasons for this are not entirely clear, but it seems to be partly related to how oxygen moves from our blood vessels to the muscles and how muscles burn energy. The precise role of age and physical fitness, as well as whether exercise can counteract the effects of ageing, is still unknown. Therefore, in this study, we aim to investigate the muscle function of both physically active and inactive young and middle-aged individuals. We hypothesise that endurance training can mitigate some of the effects of ageing.

Conditions

Aging

Keywords

Exercise; Mitochondria; Skeletal muscle

Outcome Measures

Primary Outcomes (6)

• Maximal oxygen uptake (V̇O2max)

  ml/min/kg

  Baseline (visit 1)

• Muscle volume

  cm\^3

  Baseline (visit 1)

• Muscle strength

  Newton-metre (Nm)

  Baseline (visit 1)

• Muscle power

  Watt (W)

  Baseline (visit 1)

• Muscle diffusing capacity for oxygen (DmO2)

  Differences in recovery constant k (min-1) obtained under conditions of high, medium or low O2 availability

  Baseline (visit 1) and visit 2-4. In total 4 weeks.

• Muscle mitochondrial fragmentation index (A.U.)

  Degree of fragmentation of the mitochondrial pool.

  Visit 6 muscle biopsy (+/- after 4 weeks).

Secondary Outcomes (58)

• Gas exchange and ventilatory variables (gas exchange threshold, respiratory compensation point, maximal ventilation)

  Baseline (visit 1)

• (Peak) power output

  Baseline (visit 1)

• Mean response time of the V̇O2 slope during ramp exercise

  Baseline (visit 1)

• (Maximum) heart rate (HR)

  Baseline (visit 1) and during visit 2-4 (max 4 weeks in total)

• Maximal O2 pulse

  Baseline (visit 1)

Study Arms (4)

Young, sedentary participants

* Aged between 18-30 years * Male or female * Not currently engaging in any formal exercise training or competitive sports * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise

Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy

Young endurance-trained participants

* Aged between 18-30 years * Male or female * Currently engaging in formal training (at least 3 times per week) in competitive endurance sports (i.e. running, cycling, swimming, triathlon, etc.) * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise

Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy

Middle-aged, sedentary participants

* Aged between 50-65 years * Male or female * Not currently engaging in any formal exercise training or competitive sports * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise

Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy

Middle-aged endurance-trained participants

* Aged between 50-65 years * Male or female * Currently engaging in formal training (at least 3 times per week) in competitive endurance sports (i.e. running, cycling, swimming, triathlon, etc.) * No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise

Other: Maximal exercise test; Other: 3D Ultrasound; Other: Dynamometry; Other: Exercise test and occlusions; Other: Exercise test in MRI; Procedure: Muscle biopsy

Interventions

Maximal exercise test OTHER

Participants will undertake an incremental ramp test on a cycle ergometer to determine maximal oxygen uptake (V̇O2max) and the gas exchange threshold (GET). Throughout the exercise test, muscle oxygenation and deoxygenation will be monitored by NIRS.

Middle-aged endurance-trained participants; Middle-aged, sedentary participants; Young endurance-trained participants; Young, sedentary participants

3D Ultrasound OTHER

Muscle volume and morphological characteristics will be assessed via 3D ultrasound imaging.

Middle-aged endurance-trained participants; Middle-aged, sedentary participants; Young endurance-trained participants; Young, sedentary participants

Dynamometry OTHER

To determine the contractile properties of the knee extensors, participants will perform maximal isometric and isoinertial contractions of the knee extensors on a dynamometer.

Middle-aged endurance-trained participants; Middle-aged, sedentary participants; Young endurance-trained participants; Young, sedentary participants

Exercise test and occlusions OTHER

Participants will perform a series of moderate-intensity constant power output exercise bouts on a cycle ergometer following which the recovery rates of muscle V̇O2 will be determined via a series of intermittent arterial occlusions. Throughout all tests, pulmonary gas exchange and ventilation will be determined and muscle oxygenation and deoxygenation will be monitored by NIRS.

Middle-aged endurance-trained participants; Middle-aged, sedentary participants; Young endurance-trained participants; Young, sedentary participants

Exercise test in MRI OTHER

Exercise will be performed on a custom-built magnetic resonance-compatible cycle ergometer in supine position for determination of muscle phosphocreatine recovery kinetics using 31phosphorous magnetic resonance spectroscopy \[31P-MRS\].

Middle-aged endurance-trained participants; Middle-aged, sedentary participants; Young endurance-trained participants; Young, sedentary participants

Muscle biopsy PROCEDURE

A muscle biopsy will be obtained from the vastus lateralis using a modified Bergström needle technique with suction.

Middle-aged endurance-trained participants; Middle-aged, sedentary participants; Young endurance-trained participants; Young, sedentary participants

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

15 sedentary and 15 endurance-trained young and middle-aged individuals will be recruited per age group (i.e. a total of 60 individuals spanning 4 groups). An equal balance of the sexes will be aimed for in each group. All participants will be recruited from specific social media groups, through personal networks of friends, family and colleagues, flyers and posters at local sports clubs and on the VU Campus. All testing will be conducted at the VU or in the Department of Radiology and Nuclear Medicine at Amsterdam UMC location AMC. Therefore, participants should be currently residing in or willing to travel to Amsterdam.

You may qualify if:

• In order to be eligible to participate in this study, young sedentary participants must meet all of the following criteria:
• Aged between 18-30 years
• Male or female
• Not currently engaging in any formal exercise training or competitive sports
• No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
• In order to be eligible to participate in this study, young trained participants must meet all of the following criteria:
• Aged between 18-30 years
• Male or female
• Currently engaging in formal training (at least 3 times per week) in competitive endurance sports
• No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise
• In order to be eligible to participate in this study, older sedentary participants must meet all of the following criteria:
• Aged between 50-65 years
• Male or female
• Not currently engaging in any formal exercise training or competitive sports
• No chronic health conditions likely to affect exercise tolerance or the physiological responses to exercise

You may not qualify if:

• Age that falls outside of 18-30 years (young groups) or 50-65 years (middle-aged groups)
• Inability to provide informed consent
• History of claustrophobia
• Ineligibility to perform the exercise test described in this study protocol or follow instructions
• Taking any medications known to interfere with the physiological responses to exercise, e.g. e.g. systemic corticosteroids, statins, SGLT2 inhibitors, GLP1 receptor agonists
• Contraindication for MRI (e.g. pacemaker, claustrophobia)
• Being under investigation for non-diagnosed disease at the time of investigation
• Body Mass Index (BMI) \>30 due to adiposity, since this is known to cause difficulties in obtaining muscle biopsies and NIRS measurements
• Pregnancy
• Are current smokers or have been a regular smoker within the last 12 months

Sponsors & Collaborators

• VU University of Amsterdam: lead

Study Sites (1)

Vrije Universiteit Amsterdam

Amsterdam, North Holland, 1081HV, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Muscle biopsies

MeSH Terms

Conditions

Motor Activity

Interventions

Exercise Test; Dental Occlusion; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Dentistry; Dental Physiological Phenomena; Digestive System and Oral Physiological Phenomena; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Richie Goulding, PhD

  VU University of Amsterdam

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ellen Breedveld, MSc

CONTACT

+31636318844; e.a.breedveld@vu.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: August 6, 2024
• Study Start: March 25, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)