Grant: Operating Grant: Understanding the Health Impact of Inactivity - IMHA
Research Institute of the McGill University Health Centre
$200,000.00
Unraveling the mechanisms underlying of bed rest-induced muscle atrophy and of an exercise countermeasure
EF 2018-19
Résumé
Inactivity is associated with muscle loss and decreased bone mineral density, conditions seen with aging and during spaceflights. A model of inactivity of musculoskeletal unloading mimicking lack of gravity is bed rest with head-down tilt. Our reasoning is that bed rest leads to reduced fat oxidation and increases reactive oxygen species (ROS) from the mitochondria, the power house of the cell, which stimulates intracellular mechanisms responsible for developing insulin resistance and to decrease muscle and bone masses. These mechanisms involve the activity- and energy-sensing AMPK and the food-sensing mTOR, under which there are many key factors involved in muscle protein synthesis and breakdown. At the bone level, there is decreased production of osteocalcin, a protein shown to promote insulin sensitivity and to be associated with muscle atrophy in rats. We propose to study 24 men and women of 55-65 years of age engaged in moderate-vigorous exercise. Participants will be randomized into two groups for a two-week bed rest with half of them performing one hour of daily exercise while in bed as a countermeasure. At baseline and at 3, 7 and 14 days of bed rest, we will obtain venous blood and perform muscle biopsies of the thigh to measure muscle protein synthesis and breakdown using the deuterated water method. We will also measure mitochondrial respiration and ROS production in fresh permeabilized fibers, and in frozen muscle tissue, fiber type and size and several regulating factors by western blots. We will measure osteocalcin and many hormones regulating muscle and bone mass in blood samples. Participants will undergo an oral glucose tolerance test, assessment of their body compartments and physical performance before and at the end of bed rest. We wish to uncover the mechanisms related to muscle mass loss with inactivity and in response to exercise, which should open the door to future interventions to prevent the consequences of inactivity
Programme
Operating Grant: Understanding the Health Impact of Inactivity - IMHA
Emplacement
Quebec, Canada
Type
Grant
Source
CIHR Funding Decisions Database
Tel que publié
Id
399488
Name
Morais José A
Region
Québec
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Musculoskeletal Health and Arthritis
Theme2
Clinical
Prcname2
Operating Grant : Understanding the Health Impact of Inactivity
Projecttitle
Unraveling the mechanisms underlying of bed rest-induced muscle atrophy and of an exercise countermeasure
Programtype2
Operating Grants
Orgnameinp2
Research Institute of the McGill University Health Centre
Cihramount2
$200,000
Cihrequipment2
$0
Programname2
Operating Grant: Understanding the Health Impact of Inactivity - IMHA
Keyworddelim
Autophagy; Bed Rest; Deuterated Water Method Of Protein Kinetics; Inactivity; Mitochondrial Function; Mtor Signaling Pathway; Muscle Fiber Typing; Musculoskeletal Unloading; Osteocalcin; Ubiquitin-Proteosome Pathway
Abstract
Inactivity is associated with muscle loss and decreased bone mineral density, conditions seen with aging and during spaceflights. A model of inactivity of musculoskeletal unloading mimicking lack of gravity is bed rest with head-down tilt. Our reasoning is that bed rest leads to reduced fat oxidation and increases reactive oxygen species (ROS) from the mitochondria, the power house of the cell, which stimulates intracellular mechanisms responsible for developing insulin resistance and to decrease muscle and bone masses. These mechanisms involve the activity- and energy-sensing AMPK and the food-sensing mTOR, under which there are many key factors involved in muscle protein synthesis and breakdown. At the bone level, there is decreased production of osteocalcin, a protein shown to promote insulin sensitivity and to be associated with muscle atrophy in rats. We propose to study 24 men and women of 55-65 years of age engaged in moderate-vigorous exercise. Participants will be randomized into two groups for a two-week bed rest with half of them performing one hour of daily exercise while in bed as a countermeasure. At baseline and at 3, 7 and 14 days of bed rest, we will obtain venous blood and perform muscle biopsies of the thigh to measure muscle protein synthesis and breakdown using the deuterated water method. We will also measure mitochondrial respiration and ROS production in fresh permeabilized fibers, and in frozen muscle tissue, fiber type and size and several regulating factors by western blots. We will measure osteocalcin and many hormones regulating muscle and bone mass in blood samples. Participants will undergo an oral glucose tolerance test, assessment of their body compartments and physical performance before and at the end of bed rest. We wish to uncover the mechanisms related to muscle mass loss with inactivity and in response to exercise, which should open the door to future interventions to prevent the consequences of inactivity
Competitiondate
201808
Approvedterm2
1 yr 6 mths
Pinamesdelim
Morais, José A
Approvedterm
1 an 6 mois
Cihrcontribution2
Inst of Musculoskel Hlth &Arth~ $200,000~ $0~
