HRR - Gap - M24: Characterize the time course of changes in muscle protein turnover, muscle mass, and function during long duration space flight.

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M24: Characterize the time course of changes in muscle protein turnover, muscle mass, and function during long duration space flight.

Last Published: 11/23/20 11:55:10 AM (Central)

Responsible Element: Human Health Countermeasures (HHC)

Status: Open

Description

Initial State: Skeletal muscle protein turnover is governed by the differences in rates of muscle protein synthesis versus muscle protein breakdown. Muscle atrophy occurs when there is a negative net rate of turnover of myofibrillar proteins. Understanding the role of muscle protein synthesis, breakdown and overall protein turnover during the time course of long duration space flight mission would be beneficial in making informed decisions regarding the best countermeasures approaches to implement. If countermeasures are not fully effective, strategies to address the remaining perturbing factor (reduced synthesis versus increased breakdown) would likely yield the most fruitful benefits. Current techniques for analysis of protein synthesis and breakdown require muscle biopsy samples for analysis which are prohibitive at this time because measurements or sample collections would need to be conducted at various time points with crew members aboard the International Space Station.

Interim Stages:
Identification and validation of novel technologies for measuring protein turnover
Determination of in-flight time course of changes in skeletal muscle protein synthesis, breakdown and net turnover
Establish relevance of turnover measurements to exercise prescription modifications
Determination of in-flight time course of changes in skeletal muscle mass or volume

Approach: Solicitations for novel approaches will be sought for measuring human skeletal muscle turnover using techniques that are compatible during space flight aboard the ISS. Studies using validated techniques would then be conducted during long duration missions.

Target for Closure

Establishment of a timeline for changes in muscle protein synthesis, breakdown, net muscle protein turnover, and muscle mass/volume during long duration space flight.

Mappings

Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

M24: Characterize the time course of changes in muscle protein turnover, muscle mass, and function during long duration space flight.

Active

Assessment of the Time Courses of Leg Muscle Strength and Performance Losses During Prolonged Spaceflight using MARES (Laughlin)

Task Book: Entry Unavailable
Principal Investigator: Laughlin, Mitzi

Short Title: Lower Limb Modulation - Flight

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

International Partner

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
Use the MARES device to quantify the time course of changes in muscle strength and performance of crewmember volunteers during six-month ISS missions. Establish baseline strength and performance capabilities of each participating crewmember from two pre-flight test sessions, track changes from that baseline during three in-flight test sessions, and track recovery to baseline levels during five post-flight test sessions.

Resources (Flight)

Deliverables (1)

Musculoskeletal response to a partial-gravity analog in rats: structural, functional and molecular alterations (Rutkove)

Task Book: Entry Unavailable
Principal Investigator: Rutkove, Seward

Short Title: partial-gravity analog in rats

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

Rats will be used to evaluate the potential effectiveness of artificial gravity for the prevention of muscle atrophy and weakness and loss of bone using an innovative system for partial unloading that has been developed previously for mice. Musculoskeletal response will be studied during a period of 4 weeks in adult male rats (n=14 / group) during a period of 4 weeks following exposure to different degrees of unloading representing 0.2G, 0.4G, and 0.7G as well as in fully loaded animals. Muscle and bone structure and function will be assessed, histological analyses will be performed, and measurements of muscle contraction, bone mass, microarchitecture and strength will be collected. In addition, serological and tissue molecular analyses will be perfomed to better understand the mechanisms and time course of development of these changes at different degrees of unloading. This work will also allow a more effectively understanding of the relationship between

the development of muscle atrophy and weakness and bone deterioration at varying levels of artificial gravity.

Resources (None Listed)

Deliverables (1)

Time Course of Spaceflight-Induced Adaptations in Bone Morphology, Bone Strength and Muscle Quality (Bouxsein)

Task Book: Entry Unavailable
Principal Investigator: Bouxsein, Mary

Short Title: CIPHER Musculoskeletal Adaptations - ISS

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Research Operations and Integration (ROI)

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

1.Determine changes in volumetric density, structure and strength of the proximal femur and lumbar spine following 2, 6 and 12 months of spaceflight.

2.Compute subject-specific load-to-strength ratio to estimate temporal changes in the risk of hip and vertebral fracture following 2, 6 and 12 months of spaceflight.

3.Determine changes in muscle quality following 2, 6 and 12 months of spaceflight.

Resources (Flight)

Deliverables (1)

Completed

Modulation of Muscle Function by Lower Limb Loading during Space Flight

Task Book: Entry
Principal Investigator: Laughlin, Mitzi

Short Title: Lower Limb Modulation

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Completed - Task completed and produced a deliverable

Procurement Mechanism(s):

Solicited

Aims:

Develop protocol to study astronaut volunteers before flight and on multiple occasions during flight using the MARES device to provide loading to the feet and legs as well as device that can apply pressure to the soles of the feet. The effects on muscle activation and performance associated with foot pressure alone or foot pressure plus lower limb loading will be investigated.

Integration/Unique Aspects: This entry reflects only definition phase of the grant

Resources (None Listed)

Deliverables (0)

Terminated

Development of a Muscle Adaptation in Space-flight Simulator ("MASS")

Task Book: Entry Unavailable
Principal Investigator: Blemker, Silvia

Short Title: MASS

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Terminated - A formerly active task that was stopped before its completion date due to deselection, descoping, reorganization etc.

Procurement Mechanism(s):

Solicited

Aims:

DESCOPED and then DEFUNDED due to a shift in strategic planning.

The aim is to develop a multiscale computational model that can predict changes in muscle structure and function in response to both microgravity and in-flight exercise. The modeling approach will provide a cohesive, user-friendly, and open-source framework for computational simulations at different levels of spatial scale, including: dynamic OpenSim simulations at the whole body level; finite-element simulations of muscle tissue; and agent-based simulations of muscle cells that include the biochemical and biomechanical processes that drive individual muscle cell adaptations. This level of integration is necessary because factors at all of these scales influence the degree of muscle atrophy during prolonged spaceflight but they have never been considered in isolation.

Resources (None Listed)

Deliverables (1)

Documentation:

No Documentation Available

Related Gaps (13)

M14: Indentify adjuncts to exercise countermeasures that can be used to better mitigate muscle loss.

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

M1: What is the current state of knowledge regarding exercise performance?

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

M4: Establish muscle function standards for successful completion of mission tasks.

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

M6: Develop pre-flight, in-flight, and post-flight evaluations to determine if muscle function standards are met.

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

M7: Develop the most efficient and effective exercise program for the maintenance of muscle function.

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance
	Development of a Muscle Adaptation in Space-flight Simulator ("MASS")
	Musculoskeletal response to a partial-gravity analog in rats: structural, functional and molecular alterations (Rutkove)

M9: Identify and validate exploration countermeasure hardware for the maintenance of muscle function.

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

M2: Characterize in-flight and post-flight muscle performance.

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance
	Development of a Muscle Adaptation in Space-flight Simulator ("MASS")
	Musculoskeletal response to a partial-gravity analog in rats: structural, functional and molecular alterations (Rutkove)
	Time Course of Spaceflight-Induced Adaptations in Bone Morphology, Bone Strength and Muscle Quality (Bouxsein)

M23: Determine if factors other than unloading contribute to muscle atrophy during space flight.

Common Item(s)
	Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance

Osteo 2: What is the incidence & prevalence of early onset osteoporosis or fragility fractures due to exposure to spaceflight.

Common Item(s)
	Time Course of Spaceflight-Induced Adaptations in Bone Morphology, Bone Strength and Muscle Quality (Bouxsein)

Osteo 4: We don't know the contribution of each risk factor on bone loss and recovery of bone strength, and which factors are the best targets for countermeasure application.

Common Item(s)
	Musculoskeletal response to a partial-gravity analog in rats: structural, functional and molecular alterations (Rutkove)
	Time Course of Spaceflight-Induced Adaptations in Bone Morphology, Bone Strength and Muscle Quality (Bouxsein)

Osteo 5: We need an inflight capability to monitor bone turnover and bone mass changes during spaceflight.

Common Item(s)
	Musculoskeletal response to a partial-gravity analog in rats: structural, functional and molecular alterations (Rutkove)

Osteo 6: How do skeletal changes due to spaceflight modify the terrestrial risk of osteoporotic fractures?

Common Item(s)
	Time Course of Spaceflight-Induced Adaptations in Bone Morphology, Bone Strength and Muscle Quality (Bouxsein)

Osteo 7: We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight.

Common Item(s)
	Musculoskeletal response to a partial-gravity analog in rats: structural, functional and molecular alterations (Rutkove)

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PRRs (1)

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