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EXPERIMENT INFORMATION

Nicotinamide Dinucleotide (NAD)-Boosting Strategy to Mitigate Musculoskeletal Loss During Space Exploration (Postdoctoral Fellowship) (80NSSC19K0439)
Research Area:
Cell and molecular biology
Species Studied
Scientific Name: Mus musculus Species: Mouse Strain: C57BL/6J

Description
OBJECTIVES:
Musculoskeletal loss and the associated functional impairment affect broadly, including the elderly people, patients with chronic diseases such as cancer, and astronauts. Microgravity in space breaks tissue homeostasis in skeletal muscle by activating proteolysis and inflammatory pathways, leading to muscle atrophy. SIRT1, a NAD+-dependent protein deacetylase, is a critical gene regulating metabolism and tissue homeostasis in skeletal muscle. Notably, activating SIRT1 inhibits protein degradation in skeletal muscle by counteracting the ubiquitin proteasome pathway. In addition, our recent results showed that activating SIRT1 by nicotinamide mononucleotide (NMN), an NAD+ precursor, reverses functional decline in skeletal muscle of aged mice by mimicking exercise. All of this evidence suggests that maintaining high NAD+ levels in muscle tissues is a practical and safe intervention strategy for preventing muscle atrophy. The goal of this proposal is to test if boosting NAD+ mitigates unloading-induced musculoskeletal loss. Specifically, we will investigate the following objectives.

Objective 1: Determine the effect of NMN on mitigating unloading-induced musculoskeletal loss. We will use hindimb suspension (HS) in mice to simulate microgravity-induced muscle unloading. Our hypothesis is NMN administration during unloading mitigates muscle atrophy, bone loss, and functional impairment. We will also investigate if NMN alleviates slow-to-fast fiber type shift caused by muscle unloading, which significantly reduces fatigue resistance of the slow-twitch muscles.

Objective 2: Determine if NMN improves the effectiveness of exercise during unloading. As an exercise mimetics, NAD+ promotes the beneficial effects of exercise by activating SIRT1. We propose that raising NAD+ levels during exercise confers additive benefits than does exercise alone. We will test if SIRT1 overexpression or NMN administration augment the effectiveness of exercise and further mitigate musculoskeletal loss.


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Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Additional Information
Managing NASA Center
Ames Research Center (ARC)
Responsible NASA Representative
Ames Research Center LSDA Level 3
Project Manager: Helen Stewart
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
03/01/3019
Proposal Source
2016-17 Space Biology (ROSBio) NNH16ZTT001N-FG