The primary objective of this study is to measure mitochondrial capacity using NIRS in young and older healthy males in three different muscles (vastus lateralis, gastrocnemius and the tibialis anterior) to give insights on how age-related changes…
ID
Source
Brief title
Condition
- Other condition
- Muscle disorders
Synonym
Health condition
Veroudering
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is mitochondrial capacity, measured as the rate of
recovery of muscle oxygen consumption after exercise measured using NIRS in the
vastus lateralis, gastrocnemius and tibialis anterior.
Secondary outcome
Muscle acylation status is analysed in muscle biopsies from the vastus
lateralis. Physical activity is monitored using a wearable accelerometer over a
period of seven days and a 24 hour urine is collected in order to analyse
markers of mitochondrial function in urine. Blood is collected to analyse
markers of mitochondrial function in plasma.
Background summary
Ageing is associated with a decline in muscle mitochondrial function. Measuring
muscle mitochondrial function is challenging and to routinely assess
mitochondrial function in response to exercise and dietary interventions,
practical, non-invasive and robust measurements are needed. Near-infrared
spectroscopy (NIRS) is a novel technique that allows to non-invasively measure
mitochondrial capacity in the human muscle. Although the technique is promising
for measuring mitochondrial function during ageing, it is yet be established
how age-related changes in mitochondrial function differ between different
muscle types.
Apart from monitoring mitochondrial function non-invasively, there is a need to
mechanistically understand the ageing process in the mitochondrion. The
post-translational modification (PTM) of histones and other proteins by
acylation has been identified to impact metabolism and gene transcription in
the cell. Age-related changes in metabolism are likely to affect levels of acyl
groups in the cell, hereby altering acylation patterns and regulating
transcription and protein functionality. Sirtuins are a class of enzymes that
exert deacylation activity and regulate acylation levels in the cell. Sirtuins
are dependent on the cofactor nicotinamide adenine dinucleotide (NAD). Levels
of NAD decline during ageing in humans, possibly further impacting acylation
status in the cell. The reversible nature of PTMs suggests an interesting
target for dietary and exercise interventions in vivo. Further research on how
acylation is affected by age is needed, especially in apparently ageing tissues
such as the skeletal muscle.
Study objective
The primary objective of this study is to measure mitochondrial capacity using
NIRS in young and older healthy males in three different muscles (vastus
lateralis, gastrocnemius and the tibialis anterior) to give insights on how
age-related changes in mitochondrial function differ between different muscle
types. The secondary objective is to analyse the effect of age on acylation
status of the muscle. The relationship between mitochondrial function and
acylation status will be explored. Furthermore, physical activity is monitored
using accelerometry and plasma and 24-hour urine in collected to scan for
markers of mitochondrial function.
Study design
Cross sectional study
Study burden and risks
No direct health benefits for the subjects are expected. The experimental
procedures are safe, but can cause discomfort to a certain degree. The invasive
measurements, blood sampling and muscle biopsy, can cause pain and local
hematoma or bruising. Non-invasive measurement of mitochondrial capacity using
NIRS makes use of arterial occlusions by external pressure, which can be
painful or uncomfortable and possibly could bruise the site of the occlusion.
Slight adjustments in daily life are asked from the subjects; e.g. the subject
is asked to refrain from physical activity and alcohol before the test days and
are expected to fast overnight. A financial compensation for the time
investment of ¤75 is offered when completing the study.
De Elst 1
Wageningen 6708 WD
NL
De Elst 1
Wageningen 6708 WD
NL
Listed location countries
Age
Inclusion criteria
Young
* Male, 19-25 years
* BMI 18.5-27 kg/m2
* Normal activity levels: 1-2 times per week engaged in a structured exercise session ;Elderly
* Male, 65-71 years
* BMI 18.5-27 kg/m2
* Normal activity levels: 1-2 times per week engaged in a structured exercise session
* Short physical performance battery score >6
Exclusion criteria
* (known symptoms of) Metabolic diseases, e.g. type I or II diabetes,
* Health concerns regarding respiratory and pulmonary diseases, e.g. COPD, (exercise induced) asthma and cardiovascular disease.
* Impaired physical performance (defined as short physical performance battery score < 6) (only for elderly)
* Contraindications for electrical stimulation, e.g. cardiac pacemaker
* Contraindications for muscle biopsy, e.g. usage of anticoagulants (low dose aspirin allowed)
* Regular smoker (defined as smoking >5 cigarettes per week)
* Vastus lateralis skinfold > 30mm (due to tissue penetration depth of near-infrared light)
* Haemoglobin concentrations below 8.0 mmol/L
* Usage of recreational drugs, e.g. marihuana, amphetamines and cocaine during the study (starting after first screening day)
* Recent usage (within four months) of supplements with suggestive training effects, e.g. creatine phosphate, EPO or anabolic steroids.
* Current or recent (< 2 weeks) participation in other clinical trials
* Employed or undertaking a thesis or internship at the department of Human and Animal Physiology
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL65872.081.18 |
| OMON | NL-OMON22045 |