Muscles in microgravity: Spaceflight duration impacts muscle protein stress markers

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In a caller study published successful nan diary Antioxidants, researchers analyzed musculus samples from long-duration ngo (LDM) and short-duration ngo (SDM) astronauts to analyse nan effects of spaceflight connected musculus macromolecule nitrosylation. They recovered that LDM astronauts showed close-to-normal look of sarcolemmal NOS1 (short for nitric oxide synthase type-1) and over-nitrosylation of functional proteins post- vs. preflight, indicating musculus adaptation. Further, SDM astronauts displayed s-nitrosylation of glycolytic flux proteins, tricarboxylic acerb (TCA) rhythm proteins, and respiratory concatenation proteins, indicating impaired adenosine triphosphate (ATP) accumulation and musculus contraction.

 Summit Art Creations / ShutterstockStudy: Nitrosative Stress successful Astronaut Skeletal Muscle successful Spaceflight. Image Credit: Summit Art Creations / Shutterstock


Astronauts, peculiarly during LDMs, are shown to acquisition musculus nonaccomplishment and usability decline, nan mechanisms underlying which are poorly understood. Recent investigation calls for focused studies connected molecular mechanisms of musculoskeletal disuse and adaptation, musculus and bony loss, nutrition, and workout optimization arsenic countermeasures for early heavy abstraction explorations. Long-term vulnerability to abstraction conditions is shown to induce changes successful redox genes and pathways, starring to oxidative/nitrosative accent and musculus wasting. Skeletal muscle, a awesome root of nitric oxide (NO) successful nan body, is shown to acquisition important physiological changes successful space, affecting development, growth, and workout tolerance.

In nan coming study, researchers study nan grounds from nan MUSCLE IOPSY study conducted connected nan International Space Station (ISS), which explored sarcolemmal NOS1 localization patterns and differential changes successful SNO macromolecule levels successful astronauts' soleus muscles, providing insights into nan effect of microgravity connected musculus physiology and imaginable biomarkers for monitoring musculus wellness during spaceflight.

About nan study

The coming study included a full of six antheral ISS unit members from American, Japanese, and European abstraction agencies, pinch 1 subordinate successful an SDM (9 days) and 5 successful an LDM (~180 days). The SDM astronaut did not undertake inflight exercise, arsenic opposed to LDM astronauts. Body wide indices and workout countermeasure specifications were obtained from nan participants. Pre- and post-flight biopsy samples from nan correct soleus musculus (a awesome calf skeletal muscle) were collected and analyzed. Cryosections from stiff insubstantial blocks were immunostained for NOS1, visualized pinch fluorescent secondary antibodies, and imaged utilizing a confocal microscope for subcellular awesome quantification and subjected to S-nitrosoproteomics utilizing 2-D CyDye-Maleimide differential gel electrophoresis (Nitro-DIGE). Protein recognition was performed by matrix-assisted laser desorption/ionization time-of-flight wide spectrometry (MALDI-ToF MS), and immunoblotting was conducted for selected proteins. Ribonucleic acerb (RNA) was extracted from nan samples, and quantitative PCR (qPCR) was carried retired to analyse cistron look levels of NOS1. Statistical study progressive nan usage of nan Pearson–D'Augustino normality test, paired and unpaired Student's t-test, Mann–Whitney test, and nan exertion of mendacious find rate.

Results and discussion

Two of nan 3 LDM astronauts showed a 2- to 2.5-fold alteration successful NOS1 transcript levels successful soleus musculus samples post-flight compared to preflight, while nary important alteration was observed successful nan SDM astronaut. Immunolocalization study revealed a simplification successful sarcolemma NOS1 successful nan SDM astronaut sample post-flight compared to preflight. Conversely, successful astatine slightest 2 of nan LDM astronauts, location was an summation successful subsarcolemmal NOS1 localization post-flight. However, while 1 LDM astronaut showed nary change, different LDM astronaut showed reduced NOS1 post-flight. The alteration observed successful nan SDM astronaut was prevented successful LDM astronauts, indicating nan imaginable affirmative effects of targeted inflight workout connected subsarcolemmal NOS1 look successful nan soleus muscle. Additionally, quantitative study of NOS1 macromolecule levels successful soleus lysates showed changes successful LDM astronauts compared to nan 1 successful an SDM.

Nitro-DIGE study showed differential nitrosylation patterns successful proteins associated pinch power metabolism, accent response, and musculus contraction. In nan SDM sample, 8 proteins showed important changes successful some nitrosylation and abundance. However, successful nan LDM samples, only 1 macromolecule exhibited differential nitrosylation. Notably, successful SDM, fructose-bisphosphate aldolase A and myosin ray concatenation 3 were over-nitrosylated, while successful LDM, UQCRC1 (short for Human ubiquinol cytochrome c reductase halfway macromolecule 1) showed decreased nitrosylation contempt accrued abundance. Immunoblotting indicated decreased levels of intoxicant dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR) and thioredoxin reductase 1 (TXNRD1) successful some SDM and LDM astronauts, pinch important changes observed successful ADH5 for LDM.

These findings propose analyzable alterations successful nitrosylation and macromolecule abundance successful consequence to microgravity exposure, perchance implicating nitrosative accent pathways successful musculus adjustment during spaceflight. The study limitations see a constricted number of participants, constricted biopsy samples, and nan absence of inflight non-exercise controls owed to ethical constraints.


In summary, nan study revealed that while nan inflight workout protocols connected nan ISS whitethorn partially mitigate sarcolemmal NOS1 dislocation successful nan calf muscle, over-nitrosylation of important musculus proteins and decreased levels of denitrosylase enzymes bespeak impaired redox homeostasis successful astronaut's muscles sloppy of microgravity vulnerability duration. Further study of musculus macromolecule nitrosylation patterns crossed different musculus groups is warranted to find whether these patterns bespeak protective aliases detrimental mechanisms successful microgravity adaptation. Future inflight countermeasures and betterment protocols should see nutritional supplementation to minimize muscular nitrosative accent and guarantee unit wellness and capacity during heavy abstraction exploration missions.

Journal reference:

  • Nitrosative Stress successful Astronaut Skeletal Muscle successful Spaceflight. Blottner D. et al., Antioxidants, 13(4):432 (2024), DOI: 10.3390/antiox13040432,