Aging
Conditions
Keywords
Bed rest, Exercise, Aging
Brief summary
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).
Interventions
OTHERExercise
Participants will undergo an exercise program during the 2-week bed rest period.
Sponsors
Canadian Space Agency
Canadian Institutes of Health Research (CIHR)
Canadian Frailty Network
McGill University Health Centre/Research Institute of the McGill University Health Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Randomized controlled study - Participants will be randomly allocated to the exercise or control group.
Eligibility
Sex/Gender
ALL
Age
55 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* A minimum of 20 and a maximum of 24 non-smoking participants in the age group of 55 to 65 years old, half male and half female. * Female participants must be menopausal (no menses for at least 1 year (or documented ovariectomy) and a serum FSH above 30 IU/L). * Height between 158 to 190 cm with a body mass index between 20 to 30 kg/m2. * Physically and mentally healthy subjects that will have successfully passed the psychological and medical screening appropriate for the age group. * Participation in at least 2.5 hours of exercise at a moderate to vigorous-intensity aerobic activity per week. * Willing to be assigned randomly either to the exercise or the control group.
Exclusion criteria
* Participants must be dementia-free, drug- or alcohol-addiction free, with no history of heart attacks, no thrombosis risk, no severe allergies, no hypocalcaemia, no uric acidemia, no orthostatic intolerance, no vestibular disorders, no considerable musculoskeletal issues, no chronic back pain, no head trauma, no seizures, no ulcers, no renal stones, no gastro-esophageal reflux disease or renal function disorder, no hiatus hernia, no migraines, and no mental illness. * Electrocardiogram abnormalities * Anemia * Low bone mineral density * Medication requirements that may interfere with the interpretation of the results * Recent substandard nutritional status * Claustrophobia * Special dietary requests (e.g. vegetarian, vegan or some other diet) * Sedentary people and people that are addicted to exercise * Metallic implants (pacemakers, ICDs, CRT devices, infusion pumps, cerebral artery aneurysm clips, dental implants, tissue expander etc.), osteosynthesis material * Given blood in the past 3 months before the onset of the experiment * Smoked (tobacco and/or marijuana (THC)) within 6 months prior to the start of the study * Abused drugs, medicine or alcohol within up to 30 days prior to the start of the study * Participated in another study within 2 months before study onset
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cytokines with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | 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) |
| Changes in the constitution of the oral microbiome with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | 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. |
| Changes in physical performance with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Short Physical Performance Battery test |
| Changes in dynamic balance with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Four-square step test |
| Changes in bone markers with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | 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) |
| Changes in growth factors with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | 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) |
| Changes in Fractional Synthesis Rate (FSR) with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: during HDBR period | Measurement of protein turnover. |
| Changes in sleep quality with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Sleep quality will be assessed using a 3-electrode electroencephalogram (EEG) Sleep Profiler and a wrist worn actigraphy. |
| Changes in cognition status of participants with head down bed rest (HDBR) with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | NIH Toolbox Cognition Battery (computerized) |
| Changes in emotional status of participants with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | 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. |
| Changes in brain structure with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Assessment of brain anatomy using a MRI. |
| Changes in brain function with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Measurement of neuronal, cerebrovascular, and connectivity integrity with functional MRI. |
| Changes in muscle muscle mass with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Body MRI |
| Changes in muscle fat infiltration with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Body MRI |
| Changes in adiposity with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Body MRI |
| Changes in ventricular volume of the heart with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Using a heart MRI left and right ventricular volumes will be assessed. |
| Changes in ventricular mass with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Using a heart MRI left and right ventricular mass will be assessed. |
| Changes in bone structure with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | High resolution peripheral quantitative computed tomography (HR-pQCT) |
| Changes in muscle strength with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Quantitative Muscle Dynamometry (Biodex) |
| Changes in muscle-pump baroreflex with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Supine-to-stand test |
| Changes in balance control with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Postural equilibrium control test |
| Changes in orthostatic tolerance with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Tilt test |
| Cardiac and vascular changes with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Using high frame rate ultrasound (HiFRUS) arterial wall shear stress will be assessed. |
| Changes in sleep architecture with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Using 3-electrode electroencephalogram (EEG) Sleep Profiler electrical patterns of brain activity will be measured in order to assess sleep cycles and sleep stages. |
| Changes in frailty status with HDBR with and without exercise countermeasure. | Throughput the 26-day study period: at Baseline, HDBR and Recovery periods | CLSA-FI questionnaire |
| Changes in the gut microbiome with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in aerobic capacity with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Bicycle Ergometer Test |
| Changes in body composition with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Lean muscle and fat mass will be assess using dual energy X-ray absorptiometry. |
| Changes in insulin sensitivity with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | Will measure excursion curves of glucose and insulin. |
| Changes in neuronal factors with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline, HDBR and Recovery periods | 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 |
| Changes in neuromotor function with HDBR with and without exercise countermeasure. | Throughout the 26-day study period: at Baseline and Recovery periods | Neuromuscular activity will be assessed using electromyography. |
Countries
Canada
Contacts
Primary ContactGuy Hajj Boutros
Backup ContactJosé A. Morais, MD
Outcome results
None listed