Influence of Reduced Daily Step Count and Anabolic Interventions on Muscle Protein Metabolism in Older Persons

Study Overview
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Brief Summary
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As the loss of muscle mass with aging is associated with a dysregulation of muscle protein synthesis (MPS) that is generally characterized by an 'anabolic resistance' to nutrients, the primary outcome of the trial is to investigate the effect of a mixed macronutrient beverage on post-prandial myofibrillar MPS. However, the 'anabolic resistance' of aging may be predominantly influenced by the contractile activity of skeletal muscle; for example, the investigators have demonstrated that 2 weeks of reduced habitual activity (i.e. daily step count) induces anabolic resistance in otherwise healthy older adults. In contrast, resistance exercise is well-known to enhance muscle mass and can increase the sensitivity of skeletal muscle to dietary amino acids. Therefore, all participants will undergo a 2-week reduced step count intervention combined with a unilateral leg resistance exercise protocol to induce an 'unhealthy' or 'anabolically resistant' leg and a relatively 'healthy' or 'anabolically sensitive' leg, respectively; this within subject model will be utilized to investigate the effect of the mixed macronutrient beverage in both relatively 'healthy' and 'unhealthy' older muscle. The investigators will also measure changes in muscle mass, muscle function, and cardiovascular health of both legs before and after the 2-week intervention to determine the effect of reduced activity and the protective effect of minimal, low-intensity exercise on these outcomes.

Official Title
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Efficacy of Isolated Whey and Micellar Whey Protein (+/-Citrulline) to Stimulate Protein Synthesis in 'Healthy' and 'Anabolically Resistant' Elderly Muscle

Conditions
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Older Adults, Muscle Protein Synthetic Response to Protein, Reduced Physical Activity

Intervention / Treatment
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* Other: step-reduction
* Other: step-reduction plus resistance exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoker Exclusion Criteria: Health problems such as: heart disease, rheumatoid arthritis, diabetes, poor lung function, uncontrolled hypertension, or any health conditions that might put the participant at risk for this study Failed clearance for exercise participation by the participants family physician/medical doctor Failed an exercise strength test. Regular consumption of any analgesic or anti-inflammatory drug(s), prescription or non-prescription, chronically will be excluded. Taking any medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications). Factors that may exclude a participant from an MRI scan (i.e. various implants, metal in the eyes etc) Participants who complete fewer than 5000 steps per day (as assessed by pedometer prior to the study).

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Isolated Whey Protein<br>20 g isolated whey protein + 15 g non-essential amino acids | Other: step-reduction<br>* reduce daily physical activity to less than 1500 steps per day<br>Other: step-reduction plus resistance exercise<br>* reduce physical activity to less than 1500 steps per day with thrice weekly low-load, high effort resistance exercise<br>|
| Experimental: Micellar Whey Protein<br>20 g micellar whey protein + 15 g non-essential amino acids | Other: step-reduction<br>* reduce daily physical activity to less than 1500 steps per day<br>Other: step-reduction plus resistance exercise<br>* reduce physical activity to less than 1500 steps per day with thrice weekly low-load, high effort resistance exercise<br>|
| Experimental: Micellar Whey Protein + Citrulline<br>20 g micellar whey protein + 5 g citrulline | Other: step-reduction<br>* reduce daily physical activity to less than 1500 steps per day<br>Other: step-reduction plus resistance exercise<br>* reduce physical activity to less than 1500 steps per day with thrice weekly low-load, high effort resistance exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myofibrillar fractional synthetic rate will be measured using 13C6 ring phenylalanine | analysis | 7 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body composition (lean body mass, fat mass, leg lean mass, leg fat mass) will be measured using dual energy xray absorptiometry | analysis | 14 days | 
| leg muscle strength (leg press and leg extension 1 repetition maximum [1-RM], peak knee extensor torque) will be measured using a dynamometer | analysis | 14 days | 
| vascular function (femoral blood flow, femoral artery diameter, leg pulse) will be measured using doppler ultrasound | analysis | 14 days |