Responsible Center: NASA JSC
Grant Monitor: Norsk, Peter
Solicitation / Funding Source: 2014-15 HERO NNJ14ZSA001N-MIXEDTOPICS. Appendix E: Behavioral Health & Human Health Countermeasures Topics
Grant/Contract No.: NNX16AG03G
Project Type: GROUND
No. of Post Docs: 1
No. of PhD Candidates: 0
No. of Master's Candidates: 0
No. of Bachelor's Candidates: 1
No. of PhD Degrees: 0
No. of Master's Degrees: 0
No. of Bachelor's Degrees: 0
|Human Research Program Elements:
(1) HHC:Human Health Countermeasures
|Human Research Program Risks:
(1) Arrhythmia:Risk of Cardiac Rhythm Problems
(2) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
(3) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
(4) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
|Human Research Program Gaps:
(1) CV08:Can manifestations of sub-clinical or environmentally induced cardiovascular diseases during spaceflight be predicted?
(2) M06:Develop pre-flight and in-flight evaluations to determine if muscle fitness standards are met (IRP Rev F)
(3) Osteo05:We need an inflight capability to monitor bone turnover and bone mass changes during spaceflight (IRP Rev E)
(4) SANS03:We need a set of validated and minimally obtrusive diagnostic tools to measure and monitor changes in intracranial pressure, ocular structure, and ocular function (IRP Rev I)
|Flight Assignment/Project Notes:
|| NOTE: End date is now 9/30/2019 per NSSC information (Ed., 3/12/19)
NOTE: End date is now 3/03/2019 per NSSC information (Ed., 6/20/18)
|| The overall goal of the proposed study is to identify serum and urine biomarkers that can be used to improve risk prediction for physiological manifestations due to bed rest beyond current clinical measures and known predictors. Bed rest is a well-accepted model of spaceflight (simulating microgravity) that allows for the study of a larger number of subjects than is available in spaceflight, and thus is well-suited for more rapid evaluation of countermeasures and identification of potential biomarkers associated with deconditioning and countermeasure efficacy. Our study will focus on three physiological manifestations that are prevalent in crew members on long duration spaceflight and are also observed in bed rest and are the target of countermeasures: (1) altered cardiovascular function and potential sub-clinical manifestations of cardiovascular disease; (2) bone loss and increased fracture risk; and (3) muscle atrophy and decreased muscle strength.
To achieve this goal, we are applying two complementary metabolomics approaches, targeted and untargeted, to serum and urine which were collected longitudinally (2 pre-bed rest; 2 during bed rest; 1 post bed rest) from 29 study participants who underwent a 70-day head down tilt bed rest with or without participation in countermeasures (exercise, N=10; exercise plus testosterone supplement, N=9). Because a number of physiological outcomes of bed rest may be attributed to dysregulation of mitochondrial function (e.g., respiration) and mitochondrial related glycolosis, the targeted aims of our study will focus on mitochondrial related metabolic pathways. The strength of our current proposal is to use a combination of untargeted and targeted metabolomics approaches followed by a state-of-the-art metabolomic flux assay which will characterize the functional consequence of the metabolites on mitochondrial related cellular and physiological pathways involved in the homeostasis of metabolomic function.
|Research Impact/Earth Benefits:
|| Space Research Related Impact: This study has the potential to identify novel biomarkers in plasma and urine to detect the risk for and monitor the progression of physiological outcomes induced by the spaceflight environment.
Research Impact on Earth: The study has potential to identify the sequence of metabolic events leading to disruption of metabolic pathways in individuals experiencing temporary bed rest (e.g., during pregnancy) or permanent bed rest (e.g., due to aging or disabilities). In the future, countermeasures can be developed to target these pathways.
Assay Development: We are optimizing the application of a high throughput mitochondrial flux assay (Seahorse Assay) to detect circulating factors that can alter changes in mitochondrial function (glycolysis and respiration). This assay can then be applied to investigate environmental factors impacting bioenergetics of different tissue and cells for both Earth and Space related research.