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…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Healthy ageing
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcomes are: maximal oxygen uptake (V*O2max), muscle volume,
muscle strength, muscle power, muscle diffusing capacity for oxygen (DmO2), and
indicators of mitochondrial morphology.
Secondary outcome
The secondary parameters can be categorised into the following groups of
variables: exercise capacity, mitochondrial content and morphology, ex-vivo
mitochondrial respiratory function, in vivo mitochondrial energetics, histology
and immunohistochemistry, muscle morphological variables, mitochondrial
dynamics proteins, and physical activity status. Further details are given in
the protocol section 8.1.2.
Background summary
Healthy ageing is associated with a loss of muscle mass and physical function.
This loss of physical function is underpinned by reductions ins characteristics
such as muscle strength, power, and maximal oxygen uptake (V*O2max; 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
V*O2max, 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.
Study objective
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 V*O2max.
Study design
This study will be a cross-sectional study comparing young sedentary, young
endurance-trained, middle-aged sedentary, and middle-aged endurance-trained
subjects. Assessments of muscle strength and power will be performed via
isometric and isoinertial dynamometry; muscle volume will be determined via
3D-ultrasound; exercise capacity and V*O2max will be assessed via an
incremental exercise test. DmO2 will be assessed via NIRS and 31P-MRS-derived
[phosphocreatine] recovery kinetics will be used to validate NIRS-based
assessment of DmO2. Skeletal muscle biopsies will be obtained from the vastus
lateralis muscle of the quadriceps to assess mitochondrial respiration,
morphology, and the concentrations of proteins involved in mitochondrial
dynamics.
Study burden and risks
Participants in this study will be asked to perform physical exercise tests,
give a muscle biopsy, fingertip blood samples (three times), and undergo a
series of brief (5-10 s) intermittent arterial occlusions as well as a
prolonged (120 s) arterial occlusion. There is some extent of burden and risk
associated with obtaining muscle biopsies, however, this will be mitigated by
the fact that these procedures will only be carried out by highly trained
physicians.The risks of the physical exercise measurements and fingertip blood
samples are negligible. The arterial occlusion procedures are uncomfortable,
however they are not associated with any adverse effects and are regularly used
and well-tolerated in our laboratory.
There is a significant time investment on behalf of the participants, since
participants are required to visit the laboratory on six occasions for a total
of 8 hours. Participants will receive compensation for parking, travel costs,
and will receive 100 Euros upon completion of the study. However, there are no
direct benefits related to participating in this research. The findings of this
research will provide insight into the skeletal muscle ageing process and the
mediating influence of exercise.
Van der Boechorststraat 7
Amsterdam 1081BT
NL
Van der Boechorststraat 7
Amsterdam 1081BT
NL
Listed location countries
Age
Inclusion criteria
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
In order to be eligible to participate in this study, older trained
participants must meet all of the following criteria:
• Aged between 50-65 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
Exclusion criteria
• 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
• Contraindication for MRI (e.g. pacemaker, claustrophobia; see F1
vragenlijsten screening MRI Amsterdam )
• Being under investigation for non-diagnosed disease at the time of
investigation
• Risk factors for exercise testing registered by a Dutch version of the
pre-participation questionnaire (American college of sports medicine and
American Heart association). Possible risk factors will be discussed with a
medical specialist or general practitioner before a subject can be included
• BMI >30 due to adiposity, since this is known to cause difficulties in
obtaining muscle biopsies and NIRS measurements
• Vastus lateralis adipose tissue thickness >10 mm due to difficulties in
obtaining high quality NIRS data
• Pregnancy
• Are current smokers or have been a regular smoker within the last 12 months
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85101.018.23 |