Physical activity appears to be an important lifestyle habit to achieve healthy aging by promoting autonomy and quality of life. Interestingly, the dramatic changes that the human body undergoes due to bedrest for illnesses and hospitalization are similar to those seen over decades of normal aging. Bedrest in otherwise healthy older individuals can lead to a reduction of muscle size and strength, changes in bone strength and function of the heart and blood vessels. Bedrest can also lead to changes in keeping proper balance as well as changes in processing and understanding information. All of these factors negatively affect activities of daily living leading to physical function impairment and development of frailty, a clinical condition associated with an increased risk for disease and death. The purpose of this study is to investigate whether exercise can counteract the negative effects of 2-week head tilt down bed rest on muscle function and metabolism, postural control, bone structure, orthostatic tolerance and cognitive function in adults. For this study the investigators will recruit 24 healthy men and women between 55 - 65 years of age. All subjects will spend a total of 26 days (5 days of adaption period, 14 days of bed rest with 6 degrees of downward inclination, and 7 days of recovery period) at the McGill University Health Centre (MUHC). During this study, 12 subjects will randomly undergo an exercise intervention as countermeasure during the 14 days of bed rest period and 12 will serve as control. Each subjects participation in this study will involve 1 telephone call (pre-screening) and 4 visits at the MUHC: 1 screening visit (Visit 1) followed by a 26-day long visit (Visit 2) and 2 follow-up visits (Visit 3 and Visit 4). During Visits 2 - 4 various measurements will be performed to assess sensorimotor control, muscle function and metabolism, bone structure, cardiovascular function, cognitive performance and function, and specimen collection (blood, urine, saliva, feces and muscle tissue).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
24
Participants will undergo an exercise program during the 2-week bed rest period.
Royal Victoria Hospital - Glen site
Montreal, Quebec, Canada
RECRUITINGChanges in cognition status of participants with head down bed rest (HDBR) with and without exercise countermeasure.
NIH Toolbox Cognition Battery (computerized)
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in cognition status of participants with head down bed rest (HDBR) with and without exercise countermeasure.
CLSA cognition questionnaire
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in emotional status of participants with HDBR with and without exercise countermeasure.
Positive and Negative Affect Scale \- For both scales scores can range from 10-50, with higher scores representing higher levels of positive or negative affect.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in emotional status of participants with HDBR with and without exercise countermeasure.
General Health Questionnaire (GHQ-28). * Using Likert 4-point scale with the min score being 0 and max score being 84. * Higher scores indicate a higher level of distress.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in brain structure with HDBR with and without exercise countermeasure.
Assessment of brain anatomy using a MRI.
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in brain function with HDBR with and without exercise countermeasure.
Measurement of neuronal, cerebrovascular, and connectivity integrity with functional MRI.
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in muscle muscle mass with HDBR with and without exercise countermeasure.
Body MRI
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in muscle fat infiltration with HDBR with and without exercise countermeasure.
Body MRI
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in adiposity with HDBR with and without exercise countermeasure.
Body MRI
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in ventricular volume of the heart with HDBR with and without exercise countermeasure.
Using a heart MRI left and right ventricular volumes will be assessed.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in ventricular mass with HDBR with and without exercise countermeasure.
Using a heart MRI left and right ventricular mass will be assessed.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in bone structure with HDBR with and without exercise countermeasure.
High resolution peripheral quantitative computed tomography (HR-pQCT)
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in muscle strength with HDBR with and without exercise countermeasure.
Quantitative Muscle Dynamometry (Biodex)
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in muscle strength with HDBR with and without exercise countermeasure.
Vertical jump
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in muscle-pump baroreflex with HDBR with and without exercise countermeasure.
Supine-to-stand test
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in balance control with HDBR with and without exercise countermeasure.
Postural equilibrium control test
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in orthostatic tolerance with HDBR with and without exercise countermeasure.
Tilt test
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Cardiac and vascular changes with HDBR with and without exercise countermeasure.
Using high frame rate ultrasound (HiFRUS) arterial wall shear stress will be assessed.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Cardiac and vascular changes with HDBR with and without exercise countermeasure.
Using high frame rate ultrasound (HiFRUS) arterial wall stiffness will be assessed.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Cardiac and vascular changes with HDBR with and without exercise countermeasure.
Using high frame rate ultrasound (HiFRUS) cardiac mass will be assessed.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Cardiac and vascular changes with HDBR with and without exercise countermeasure.
Using high frame rate ultrasound (HiFRUS) patterns of blood flow will be assessed.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in Fractional Synthesis Rate (FSR) with HDBR with and without exercise countermeasure.
Measurement of protein turnover.
Time frame: Throughout the 26-day study period: during HDBR period
Changes in sleep quality with HDBR with and without exercise countermeasure.
Sleep quality will be assessed using a 3-electrode electroencephalogram (EEG) Sleep Profiler and a wrist worn actigraphy.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in sleep architecture with HDBR with and without exercise countermeasure.
Using 3-electrode electroencephalogram (EEG) Sleep Profiler electrical patterns of brain activity will be measured in order to assess sleep cycles and sleep stages.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in frailty status with HDBR with and without exercise countermeasure.
CLSA-FI questionnaire
Time frame: Throughput the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in the gut microbiome with HDBR with and without exercise countermeasure.
To assess gut microbiome, stool samples will be collected and targeted sequencing of the variable regions 4 and 5 (V4-V5) of the 16S ribosomal RNA gene will be performed on an Illumina MiSeq.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in the constitution of the oral microbiome with HDBR with and without exercise countermeasure.
To assess oral microbiome, saliva samples will be collected and targeted sequencing of the variable regions 4 and 5 (V4-V5) of the 16S ribosomal RNA gene will be performed on an Illumina MiSeq.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in physical performance with HDBR with and without exercise countermeasure.
Short Physical Performance Battery test
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in physical performance with HDBR with and without exercise countermeasure.
Timed-up-and-Go test
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in dynamic balance with HDBR with and without exercise countermeasure.
Four-square step test
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in bone markers with HDBR with and without exercise countermeasure.
The following bone markers will be assessed using ELISA kits: * Total osteocalcin * Undercarboxylated osteocalcin * Sclerostin * NTX (N-terminal Telopeptide) * CTX (C-terminal telopeptide) * Bone Specific Alkaline Phosphatase (BSAP) * Procollagen type 1 amino-terminal propeptide (P1NP)
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in growth factors with HDBR with and without exercise countermeasure.
The following growth factors will be measured with Multiplex: * Basic fibroblast growth factor * Granulocyte colony-stimulating factor (G-CSF) * Granulocyte-macrophage colony-stimulating factor (GM-CSF) * Platelet-derived growth factor BB (PDGF-BB) * Transforming growth factor β (TGF-β) * Vascular endothelial growth factor (VEGF)
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in cytokines with HDBR with and without exercise countermeasure.
The following cytokines will be measured with Multiplex: * Eotaxin * Interferon gamma (IFN-γ) * IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17 * Tumour necrosis factor (TNF-α) * Interferon gamma- induced protein 10 (IP-10) * Monocyte chemoattractant protein 1 (MCP-1) * Macrophage inflammatory protein-1α (MIP-1α) * Macrophage inflammatory protein-1β (MIP-1β)
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in neuromotor function with HDBR with and without exercise countermeasure.
Neuromuscular activity will be assessed using electromyography.
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in aerobic capacity with HDBR with and without exercise countermeasure.
Bicycle Ergometer Test
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in body composition with HDBR with and without exercise countermeasure.
Lean muscle and fat mass will be assess using dual energy X-ray absorptiometry.
Time frame: Throughout the 26-day study period: at Baseline and Recovery periods
Changes in insulin sensitivity with HDBR with and without exercise countermeasure.
Will measure excursion curves of glucose and insulin.
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Changes in neuronal factors with HDBR with and without exercise countermeasure.
The following bone markers will be assessed using ELISA kits: * Neurofilament light chain * Glial fibrillary acidic protein * Myelin basic protein * Total tau * Aβ1-40 * Aβ1-42 * BDNF
Time frame: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
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