Exploring the Metabolic and Molecular Basis of Age-related Declines in Human Skeletal Muscle Regenerative Capacity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Change from baseline in protein synthesis (fractional synthesis rate) in response to eccentric exercise
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •16-30 kg/m2 BMI
- •Sedentary
- •18-28 years or 65-75 years
排除标准
- •Active cardiovascular disease
- •Cerebrovascular disease including previous stroke or aneurysm
- •Respiratory disease including pulmonary hypertension or chronic obstructive pulmonary disease
- •Metabolic disease including:
- •hyper/ hypo parathyroidism or thyroidism
- •Cushing's disease
- •Type 1 or 2 diabetes
- •Active inflammatory bowel disease
- •Renal disease
- •Malignancy
- •Recent steroid treatment (within 6 months), or hormone replacement therapy
- •Clotting dysfunction
- •Musculoskeletal or neurological disorders medication that affects muscle metabolism ie. paracetamol or non steroidal anti inflammatories (NSAID's)
结局指标
主要结局
Change from baseline in protein synthesis (fractional synthesis rate) in response to eccentric exercise
时间窗: Up to one week after exercise
次要结局
未报告次要终点