Human Skeletal Muscle Response to 5 Days of Bedrest in Young Adults

Skeletal muscle plays a critical role in physical function and metabolic health, with its maintenance driven by the balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). During periods of disuse, such as illness or injury, MPS declines while MPB remains relatively unchanged, leading to muscle loss and atrophy. Short-term disuse, such as bedrest, is commonly experienced through hospitalization, and can result in rapid declines in muscle mass and strength, typically affecting the lower limbs to a greater extent. At the molecular level, bed rest significantly reduces MPS, with durations as little as 3 days showing drastic impairment in skeletal muscle turnover. Additionally, short-term periods of disuse have shown to blunt mitochondrial respiration, affecting the ability for skeletal muscle to produce energy for proper funcitoning and metabolic processes. Diminished skeletal muscle metabolic function directly impacts whole-body metabolic health. Periods of bedrest between 5 and 7 days have shown to decrease whole-body glucose tolerance, increase insulin resistance, and decrease insulin-stimulated leg glucose uptake. All together, these contribute to decreased skeletal muscle mass and strength, and diminished metabolic function, contributing to a decline in overall physical function, health, and well-being. Current studies on short-term bed rest (ex. 5 days) in young adults are limited, and existing research has focused on simulated microgravity models rather than horizontal bed rest, which better represents clinical scenarios. Additionally, no study to our knowledge has explored how the molecular mechanisms that drive MPS change over the course of a 5-day bedrest period. This highlights a need to explore if there are differences in the attrition of synthesis rates of the different protein pools in skeletal muscle (ex. myofibrillar, sarcoplasmic, and mitochondrial).

The purpose of the present study is to investigate changes in leg muscle mass, strength, and whole-body insulin sensitivity over five days of bed rest, as well as examine the time-course changes in molecular mechanisms underlying skeletal muscle turnover. The investigators hypothesize that, compared to the control period, quadriceps muscle size (volume and cross-sectional area), strength/power/fatigue resistance, and whole-body insulin sensitivity will decrease following bedrest. The investigators hypothesize that these outcomes will be linked to decreases in mitochondrial respiratory function and impaired fractional synthetic rates of muscle proteins.

In this repeated-measures design, participants will undergo a five day baseline control period followed by five days of bed rest to compare changes from bedrest to their own free-living control period.

Findings from this study will help inform future research on the impact of short-term, clinically-relevant, bedrest in young adults and aid in the development of targeted interventions to mitigate declines in muscle mass from occurring from acute bouts of muscle disuse.

• Muscle strength [Time frame: Day -14, -9, and 5]
• Knee extensor power [Time frame: Day -14, -9, and 5]
• Muscle fatiguability [Time frame: Day -14, -9, and 5]
• Muscle cross-sectional area [Time frame: Day 0 and 5]
• Muscle protein synthesis [Time frame: Day -5 to 0, day 0 to 1, day 0 to 3, day 0 to 5, day 1 to 3, day 1 to 5, and day 3 to 5.]
• 2-hour plasma glucose incremental area under the curve [Time frame: Aggregate 2-hour window on day -5, 0, and 5]
• 2- hour plasma insulin incremental area under the curve [Time frame: Aggregate 2-hours on day -5, 0, and 5]
• Postprandial glucose oxidation [Time frame: Aggregate 3 hours during the mixed meal tolerance test on day -5, 0, and 5]
• Matsuda Index [Time frame: 2-hours on day -5, 0, and 5]
• Mitochondrial Respiratory Function [Time frame: Day -5, 1, 3, and 5]
• Expression of Translational Factors Related to Skeletal Muscle Protein Synthesis [Time frame: Day 0, 1, 3, and 5]
• Plasma glucose concentration [Time frame: 2-hour mixed meal tolerance test on day -5, 0, and 5]