NCT06539078

Skeletal Muscle Mitochondria in Ageing

Exercise as a Countermeasure Against the Effects of Ageing on Muscle Mitochondria, Diffusive Oxygen Transport and Muscle Volume

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 60 (estimated)
• Sponsor: VU University of Amsterdam · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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.

Detailed description

Healthy ageing is associated with a loss of muscle mass and physical function. This loss of physical function is underpinned by reductions in characteristics such as muscle strength, power, and maximal oxygen uptake (V̇O2max; reflecting exercise capacity). However, the causal contributors to these age-associated impairments, and the role of exercise training status in mitigating them, remain poorly defined. Skeletal muscle mitochondrial function has been proposed to be a key contributor to age-associated effects on physical function, however many conflicting results are present in the extant human literature. Moreover, diffusion of oxygen from capillaries to mitochondria is a key determinant of V̇O2max, however, whether the skeletal muscle diffusive capacity for oxygen (DmO2) declines with age is unknown. A new technique utilizing near-infrared spectroscopy (NIRS) will enable the non-invasive assessment of skeletal muscle diffusive capacity in young and elderly subjects for the first time to resolve this issue. The primary aims of this study are therefore to 1) compare DmO2 derived via NIRS between young sedentary, young endurance-trained, older sedentary, and older endurance-trained subjects; 2) to compare non-invasive (i.e. with NIRS and 31phosphorous magnetic resonance spectroscopy \[31P-MRS\]) and invasive (i.e. measures of mitochondrial morphology and respiration obtained by skeletal muscle biopsy) markers of mitochondrial function between the same groups, and 3) to assess the relationships between DmO2, mitochondrial measures and assessments of capillarization with functional measurements of muscle strength, power, and V̇O2max.

Conditions

• Aging

Interventions

Type	Name	Description
OTHER	Maximal exercise test	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.
OTHER	3D Ultrasound	Muscle volume and morphological characteristics will be assessed via 3D ultrasound imaging.
OTHER	Dynamometry	To determine the contractile properties of the knee extensors, participants will perform maximal isometric and isoinertial contractions of the knee extensors on a dynamometer.
OTHER	Exercise test and occlusions	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.
OTHER	Exercise test in MRI	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 \[31P-MRS\].
PROCEDURE	Muscle biopsy	A muscle biopsy will be obtained from the vastus lateralis using a modified Bergström needle technique with suction.

Timeline

• Start date: 2024-03-25
• Primary completion: 2025-12-01
• Completion: 2026-12-01
• First posted: 2024-08-06
• Last updated: 2024-08-06

Locations

1 site across 1 country: Netherlands