Loss of muscle mass is common phenotypic trait of muscular disuse and ageing. The loss of muscle mass affects, among others, the ability to maintain homeostasis of glucose metabolism and the energy reservoir in catabolic conditions, while also affecting mechanical muscle function which can cause detrimental impairments in general functional status and hence quality of life. However, a limited amount of research has attempted to elucidate molecular regulators of muscle mass loss following bed rest in older individuals and across genders. Consequently, the mechanistic drivers are unresolved and there are currently no effective therapeutic strategies to counteract muscle wasting and loss of function in individuals submitted to bed rest e.g. during hospitalization. Purpose The purpose is to examine the effects of 5 days of bed rest on muscle mass, including myofibrillar protein synthesis and breakdown, and muscle function, and elucidate molecular regulators of muscle mass loss and metabolic pathways, while also investigating if potential negative effects can be counteracted by daily NeuroMuscular Electrical Stimulation (NMES) across different age and genders. Methods The study is designed as a randomized controlled cross-over 5-day bed rest study including a group of healthy young (18-30 years) and healthy old (65-80 years) men and women. Participants will receive daily electrical stimulation (NMES) of the thigh muscles (30 min x 3/day) on one leg (ES), while the other leg serves as a control (CON). Participants will be tested at baseline (pre) and after (post) intervention for muscle strength, muscle power, balance, and muscle activation. Blood samples are collected at several time points and muscle biopsies are sampled pre- and post-intervention along with assessment of whole-body muscle mass and thigh muscle mass. Scientific exposition The results from the study can potentially provide insight into the adaptive mechanisms associated with NMES training and muscular disuse on both cellular- and whole-body level. The understanding of the underlying mechanisms is crucial for the application of NMES in a therapeutic context and will furthermore help us understand the basic mechanism regulating the skeletal muscle mass during both training and muscular disuse. Overall, the results can potentially help establishing treatments to counteract loss of muscle mass, muscle function and muscle health during periods of muscular disuse.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
32
5 days of strict bed rest
Unilateral neuromuscular electrical stimulation (m. Quadriceps)
Bispebjerg Hospital
Copenhagen, Denmark
RECRUITINGChange in Myofiber cross-sectional area
Histochemical analysis of type I and type II myofiber cross-sectional area
Time frame: Change from baseline after bed rest intervention
Assessment of myofibrillar protein synthesis
Quantification of myofibrillar protein synthesis using the stable-isotope amino acid tracer deuterium oxide (D2O)
Time frame: Assessed during the period from pre-intervention biopsies (day 0, first day of bed rest) to post-intervention biopsies (day 5, last day and cessation of bed rest)
Change in maximal isometric muscle strength and superimposed twitch
Maximal isometric voluntary quadriceps strength combined with the superimposed twitch technique to assess maximal strength and voluntary muscle activation
Time frame: Change from baseline after bed rest intervention
Change in total Akt protein assessed by Western blot
Assessment of Akt protein by Western Blot analysis using muscle tissue from vastus lateralis
Time frame: Change from baseline after bed rest intervention
Change in total mTOR protein assessed by Western blot
Assessment of mTOR protein by Western Blot analysis using muscle tissue from vastus lateralis
Time frame: Change from baseline after bed rest intervention
Change in total MuRF-1 protein assessed by Western blot
Assessment of MuRF-1 protein by Western Blot analysis using muscle tissue from vastus lateralis
Time frame: Change from baseline after bed rest intervention
Change in total Atrogin-1 protein assessed by Western blot
Assessment of Atrogin-1 protein by Western Blot analysis using muscle tissue from vastus lateralis
Time frame: Change from baseline after bed rest intervention
Change in total myostatin protein assessed by Western blot
Assessment of myostatin protein by Western Blot analysis using muscle tissue from vastus lateralis
Time frame: Change from baseline after bed rest intervention
Change in quadriceps muscle morphology and architecture by ultrasound scan
Ultrasound scan of rectus femoris and vastus lateralis muscle thickness and of vastus lateralis pennation angle
Time frame: Change from baseline after bed rest intervention
Change in body composition by DEXA scan
Assessment of whole body and regional lean mass and fat
Time frame: Change from baseline after bed rest intervention
Change in leg extensor power
Muscle power of the lower extremities assessed using the Nottingham power rig
Time frame: Change from baseline after bed rest intervention
Change in sway - postural balance
Measurement of displacement of center of pressure during unilateral and bilateral stance
Time frame: Change from baseline after bed rest intervention
Change in triglycerides
Fasting blood samples are collected for analysis of triglycerides
Time frame: Day 0, day 2, day 4 and day 5
Change in cholesterol
Fasting blood samples are collected for later analysis of cholesterol
Time frame: Day 0, day 2, day 4 and day 5
Change in C-reactive protein (CRP)
Fasting blood samples are collected for analysis of CRP values
Time frame: Day 0, day 2, day 4 and day 5
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