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      Incorporation of omics analyses into artificial gravity research for space exploration countermeasure development

      review-article
      , ,
      Metabolomics
      Springer US
      Omics, Gravity, Artificial gravity, Space flight, Astronaut, Countermeasures

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          Abstract

          The next major steps in human spaceflight include flyby, orbital, and landing missions to the Moon, Mars, and near earth asteroids. The first crewed deep space mission is expected to launch in 2022, which affords less than 7 years to address the complex question of whether and how to apply artificial gravity to counter the effects of prolonged weightlessness. Various phenotypic changes are demonstrated during artificial gravity experiments. However, the molecular dynamics (genotype and molecular phenotypes) that underlie these morphological, physiological, and behavioral phenotypes are far more complex than previously understood. Thus, targeted molecular assessment of subjects under various G conditions can be expected to miss important patterns of molecular variance that inform the more general phenotypes typically being measured. Use of omics methods can help detect changes across broad molecular networks, as various G-loading paradigms are applied. This will be useful in detecting off-target, or unanticipated effects of the different gravity paradigms applied to humans or animals. Insights gained from these approaches may eventually be used to inform countermeasure development or refine the deployment of existing countermeasures. This convergence of the omics and artificial gravity research communities may be critical if we are to develop the proper artificial gravity solutions under the severely compressed timelines currently established. Thus, the omics community may offer a unique ability to accelerate discovery, provide new insights, and benefit deep space missions in ways that have not been previously considered.

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          Most cited references63

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          Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network.

          The PGC-1 family of regulated coactivators, consisting of PGC-1α, PGC-1β and PRC, plays a central role in a regulatory network governing the transcriptional control of mitochondrial biogenesis and respiratory function. These coactivators target multiple transcription factors including NRF-1, NRF-2 and the orphan nuclear hormone receptor, ERRα, among others. In addition, they themselves are the targets of coactivator and co-repressor complexes that regulate gene expression through chromatin remodeling. The expression of PGC-1 family members is modulated by extracellular signals controlling metabolism, differentiation or cell growth and in some cases their activities are known to be regulated by post-translational modification by the energy sensors, AMPK and SIRT1. Recent gene knockout and silencing studies of many members of the PGC-1 network have revealed phenotypes of wide ranging severity suggestive of complex compensatory interactions or broadly integrative functions that are not exclusive to mitochondrial biogenesis. The results point to a central role for the PGC-1 family in integrating mitochondrial biogenesis and energy production with many diverse cellular functions. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. Copyright © 2010 Elsevier B.V. All rights reserved.
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            Glucocorticoid-induced skeletal muscle atrophy.

            Many pathological states characterized by muscle atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the muscle atrophy observed in these conditions. GC-induced muscle atrophy is characterized by fast-twitch, glycolytic muscles atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced muscle atrophy results from increased protein breakdown and decreased protein synthesis. Increased muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in muscle protein turnover could be explained by changes in the muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a muscle anabolic growth factor and Myostatin, a muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced muscle atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres.

              The primary goal of this study was to determine the effects of prolonged space flight (180 days) on the structure and function of slow and fast fibres in human skeletal muscle. Biopsies were obtained from the gastrocnemius and soleus muscles of nine International Space Station crew members 45 days pre- and on landing day (R+0) post-flight. The main findings were that prolonged weightlessness produced substantial loss of fibre mass, force and power with the hierarchy of the effects being soleus type I > soleus type II > gastrocnemius type I > gastrocnemius type II. Structurally, the quantitatively most important adaptation was fibre atrophy, which averaged 20% in the soleus type I fibres (98 to 79 μm diameter). Atrophy was the main contributor to the loss of peak force (P(0)), which for the soleus type I fibre declined 35% from 0.86 to 0.56 mN. The percentage decrease in fibre diameter was correlated with the initial pre-flight fibre size (r = 0.87), inversely with the amount of treadmill running (r = 0.68), and was associated with an increase in thin filament density (r = 0.92). The latter correlated with reduced maximal velocity (V(0)) (r = 0.51), and is likely to have contributed to the 21 and 18% decline in V(0) in the soleus and gastrocnemius type I fibres. Peak power was depressed in all fibre types with the greatest loss (55%) in the soleus. An obvious conclusion is that the exercise countermeasures employed were incapable of providing the high intensity needed to adequately protect fibre and muscle mass, and that the crew's ability to perform strenuous exercise might be seriously compromised. Our results highlight the need to study new exercise programmes on the ISS that employ high resistance and contractions over a wide range of motion to mimic the range occurring in Earth's 1 g environment.
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                Author and article information

                Contributors
                mschmidtphd@patternanalysis.org
                thomas.j.goodwin@nasa.gov
                ralph.pelligra-1@nasa.gov
                Journal
                Metabolomics
                Metabolomics
                Metabolomics
                Springer US (New York )
                1573-3882
                1573-3890
                20 January 2016
                20 January 2016
                2016
                : 12
                : 36
                Affiliations
                [ ]Sovaris Aerospace, LLC, Advanced Pattern Analysis & Countermeasures Group, Research Innovation Center, Colorado State University, 3185 Rampart Road, Fort Collins, CO 80521 USA
                [ ]Disease Modeling and Tissue Analogues Laboratory, Biomedical Research and Environmental Sciences Division, NASA Lyndon B. Johnson Space Center, Houston, TX 77058 USA
                [ ]Chief Medical Officer, NASA Ames Research Center, Moffett Field, CA USA
                Article
                942
                10.1007/s11306-015-0942-0
                4718941
                29a149bc-6150-4e03-a48a-579d0dc9b0bd
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 16 September 2015
                : 30 October 2015
                Categories
                Review Article
                Custom metadata
                © Springer Science+Business Media New York 2016

                Molecular biology
                omics,gravity,artificial gravity,space flight,astronaut,countermeasures
                Molecular biology
                omics, gravity, artificial gravity, space flight, astronaut, countermeasures

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