Healthy Clinical Trial
Official title:
Exploring the Metabolic and Molecular Basis of Age-related Declines in Human Skeletal Muscle Regenerative Capacity
The aim of this study is to understand how healthy muscle repairs in response to eccentric
exercise by evaluating functional, metabolic and molecular measures. Furthermore, this study
will aim to understand the repair mechanisms in elderly healthy muscle following eccentric
exercise by evaluating the same measures and highlighting age-related differences in repair
mechanisms which may account for the age-related loss in muscle mass. It is hypothesised
that elderly muscle will have a lesser/ blunted repair process compared to young muscle.
To meet the aims of this study and to answer the hypothesis, this study protocol is as
follows:
Baseline functional, metabolic and molecular values are obtained via functional testing and
a muscle biopsy. Participants then perform eccentric exercise designed to induce functional
decline and muscle soreness and the contralateral leg performs concentric exercise which
isn't designed to induce soreness or functional decline. Using a time-course, various
metabolic and molecular measures are taken prior to and up to 7 days post exercise to
understand the mechanisms underlying muscle repair. In addition the use of a novel amino
acid tracer (D2O) will allow for synthesis measures over the duration of the study rather
than the typical tracer techniques which only capture ~12 hours of synthesis.
Participation in this study requires participants to attend the laboratory fasted on 5
occasions spread over a period of 12 days.
Participants will report to the laboratory on the first visit for a blood sample and muscle
biopsy. In order to measure muscle metabolism participants will also consume 'heavy water',
which will also require participants to provide daily saliva swabs.
After 96 hours participants will be asked to arrive at the laboratory to perform a bout of
heavy exercise on one leg to induce sensations of muscle soreness in the days following
exercise. Investigators will then collect a blood sample and muscle biopsy from the
exercised leg and do exercise tests. After this, participants will perform another bout of
exercise on the other leg that will also be followed immediately by a blood sample, muscle
biopsy and exercise tests. This second exercise bout is not designed to induce sensations of
muscle soreness. After 5 hours , exercise tests will be performed and a further blood sample
and biopsies from both legs will be collected.
Approximately, 21 hours after exercise (visit 3) participants will be asked to return to the
lab for a short infusion (2.5 hour duration) of 2-deoxyglucose (2DOG), which allows
investigators to measure glucose uptake. After the infusion, a blood and a muscle biopsy
will be taken from each leg followed by exercising testing. Participants will then report
back to the laboratory for exercise testing, a blood sample and a single muscle biopsy from
both legs at 72 (visit 4) and 168 hours (visit 5) after the initial exercise session.
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Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label
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