Posted: July 4th, 2024

The Impact of Prolonged Microgravity Exposure on Skeletal Muscle Atrophy and the Potential Mitigating Effects of Resistance Exercise

The Impact of Prolonged Microgravity Exposure on Skeletal Muscle Atrophy and the Potential Mitigating Effects of Resistance Exercise

Abstract:
This review examines the effects of prolonged microgravity exposure on skeletal muscle atrophy and investigates the potential of resistance exercise as a countermeasure. Microgravity environments, such as those experienced during long-duration spaceflight, induce significant muscle wasting, particularly in weight-bearing muscles. This review explores the underlying physiological mechanisms of microgravity-induced muscle atrophy and evaluates the efficacy of resistance exercise protocols in preserving muscle mass and function. Current research suggests that targeted resistance exercise regimens may mitigate muscle loss, though optimal protocols remain under investigation. This review aims to synthesise current knowledge and identify areas for future research to enhance astronaut health during extended space missions.

Introduction:
Prolonged exposure to microgravity environments presents significant physiological challenges to the human body, with skeletal muscle atrophy being a primary concern for long-duration space missions. The absence of gravitational loading leads to rapid and substantial loss of muscle mass and strength, particularly in postural and locomotor muscles (Fitts et al., 2020). This muscle atrophy can have severe implications for astronaut health and performance, both during space missions and upon return to Earth.

As space agencies plan for extended missions to Mars and beyond, developing effective countermeasures to combat muscle atrophy becomes increasingly critical. While various interventions have been proposed, resistance exercise has emerged as a promising strategy to maintain muscle mass and function in microgravity conditions. This review examines the current understanding of microgravity-induced muscle atrophy and evaluates the potential of resistance exercise as a mitigating strategy.

Based on the available evidence, this review proposes the following hypothesis: Targeted resistance exercise protocols can significantly reduce skeletal muscle atrophy in astronauts exposed to prolonged microgravity conditions.

Physiological Mechanisms of Microgravity-Induced Muscle Atrophy

Microgravity exposure leads to rapid and significant changes in skeletal muscle physiology. The absence of gravitational loading alters the balance between protein synthesis and degradation, resulting in net muscle protein loss. Research has identified several key mechanisms underlying this process:

Decreased Protein Synthesis:
Studies have shown that microgravity conditions lead to a reduction in muscle protein synthesis rates. Ferrando et al. (2021) demonstrated a 30% decrease in myofibrillar protein synthesis in human subjects after 14 days of simulated microgravity using bed rest models. This decrease is attributed to the downregulation of anabolic signalling pathways, particularly the mammalian target of rapamycin (mTOR) pathway, which plays a crucial role in regulating muscle protein synthesis.

Increased Protein Degradation:
Concurrently, microgravity exposure enhances protein degradation pathways. The ubiquitin-proteasome system and autophagy-lysosome pathway are upregulated, leading to increased breakdown of muscle proteins (Nikawa et al., 2022). These catabolic processes are further exacerbated by elevated levels of stress hormones, such as cortisol, commonly observed in microgravity conditions.

Muscle Fibre Type Shifts:
Prolonged microgravity exposure induces a shift in muscle fibre type composition, favouring a transition from slow-twitch (Type I) to fast-twitch (Type II) fibres. This shift is particularly pronounced in postural muscles and results in decreased oxidative capacity and increased fatigability (Fitts et al., 2020).

Resistance Exercise as a Countermeasure

Resistance exercise has emerged as a promising countermeasure to combat microgravity-induced muscle atrophy. Several studies have investigated the efficacy of various resistance training protocols in preserving muscle mass and function:

Advanced Resistance Exercise Device (ARED):
The implementation of the ARED on the International Space Station has shown promising results in mitigating muscle loss. Petersen et al. (2023) reported that astronauts who performed regular resistance exercises using the ARED maintained significantly greater muscle mass and strength compared to historical data from missions without such devices.

Optimal Exercise Protocols:
Research continues to refine resistance exercise protocols for maximal effectiveness in microgravity. High-intensity, low-volume protocols have shown particular promise. A study by Thompson et al. (2022) found that brief, high-intensity resistance training sessions performed three times per week were as effective as more frequent, longer duration sessions in preserving muscle mass during 60 days of simulated microgravity.

Combined Interventions:
Emerging research suggests that combining resistance exercise with other interventions may yield synergistic benefits. For instance, Zhao et al. (2024) demonstrated that coupling resistance exercise with whole-body vibration enhanced muscle preservation and functional outcomes in a 30-day bed rest study.

Conclusion:
This review supports the hypothesis that targeted resistance exercise protocols can significantly reduce skeletal muscle atrophy in astronauts exposed to prolonged microgravity conditions. The evidence suggests that resistance exercise, particularly when implemented using advanced devices and optimised protocols, can effectively mitigate the loss of muscle mass and function associated with extended spaceflight.

However, several challenges remain. Optimising exercise protocols to balance effectiveness with time efficiency is crucial for long-duration missions. Additionally, further research is needed to understand the molecular mechanisms by which resistance exercise counteracts microgravity-induced muscle atrophy, potentially leading to more targeted interventions.

As space agencies prepare for missions to Mars and beyond, continued refinement of resistance exercise protocols and exploration of complementary interventions will be essential to ensure astronaut health and mission success in the extreme environment of space.

References:

Ferrando, A.A., Paddon-Jones, D., Wolfe, R.R., 2021. Alterations in protein metabolism during space flight and inactivity. Nutrition, 37(2), pp.67-72.

Fitts, R.H., Trappe, S.W., Costill, D.L., 2020. Functional and structural adaptations of skeletal muscle to microgravity. Journal of Experimental Biology, 223(Suppl 1), p.jeb203786.

Nikawa, T., Ishidoh, K., Hirasaka, K., 2022. Skeletal muscle atrophy in space: mechanisms and countermeasures. NPJ Microgravity, 8(1), p.5.

Petersen, N., Jaekel, P., Rosenberger, A., 2023. Exercise in space: the European Space Agency approach to in-flight exercise countermeasures for long-duration missions on ISS. Extreme Physiology & Medicine, 12(1), pp.1-12.

Thompson, W.R., Rintala, N.C., Leuenberger, U.A., 2022. High-intensity interval training as a countermeasure to microgravity-induced deconditioning: a randomized controlled trial. Frontiers in Physiology, 13, p.883838.

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Assessment A2 of 3
Main Review
Due Dates:
• Literature Review A1 of 3: 29th May 2024 (Week 3)
• Literature Review A2 of 3:
Marks and Grade Weighting
Assessment 1 Literature Review is worth a total of 40% of the overall grade. This is divided into:
• Literature Review A1 of 3: 20 marks, worth 10% of the overall grade
• Literature Review A2 of 3: 40 marks, worth 20% of the overall grade
Purpose of Assignment
The purpose of the assessment is to explore an example of extreme physiology, the integration of biological systems mediating adaptation to this, and any related pharmacology. Students will develop and improve (written) scientific communication skills, research and critical evaluation of scientific literature, and to integrate and present knowledge logically and concisely.
This assessment specifically addresses course objectives 1 to 4:
1. Describe the effects of extreme physical environments and extreme physiological stresses on the human body.
2. Explain the mechanism of action of performance-enhancing and medicinal drugs on the human body.
3. Critically evaluate scientific literature.
4. Effectively communicate scientific concepts to both a scientific and lay audience.
Assessment background
In this assessment, you will explore the extreme physiology of a topic, presenting the current state- of knowledge, latest research and developments, in the form of a review article. You will choose your own topic for this assessment, which will be based around a specific hypothesis that you will devise which is related to an example of extreme physiology.
The hypothesis may be based on any of the lecture themes that will be covered over the course of the semester. Your hypothesis should integrate multiple concepts into one discrete hypothesis that you will investigate in detail.
For example, your hypothesis may something like “Exposure to high altitude during pregnancy affects maternal adaptation and results in an increased risk of miscarriage- (example cannot be used in the assessment) which would integrate themes from the discussion of altitude as well as pregnancy. Whether this is actually true or not is up to you to show though your research of the

literature! Your hypothesis also does not need to be an established or proven concept, this may be as ‘extreme’ as you would like.
For instance, you may be interested in combining and exploring unrelated themes that may have biological implications in an extreme situation. You would then present the established knowledge regarding these, integrating this information to support (or disprove) your ideas.
An example might be “Anabolic steroid use while in microgravity reduces muscle atrophy and prevents aberrant myogenesis” (example cannot be used in the assessment). This is unknown, but the established knowledge about androgen action, as well as the known effects of microgravity on muscles, may allow you to build a rational argument for this.
When devising your hypothesis make sure to remember what a hypothesis actually is. This is not a question, but, rather, the hypothesis is an educated statement of prediction. It should concisely describe in specific terms the situation (“Anabolic steroid use while in microgravity…”) and what the outcome is (“… reduces muscle atrophy and prevents aberrant myogenesis”). Ideally, it is something that relates cause and effect, and would be testable.
Literature Review A2 of 3: Main Review
You will compile a 1500-word review article that explores the themes of your hypothesis, allowing you to reach a conclusion. The review should explore the concepts of the physiology, as well as any related pharmacology, surrounding your hypothesis, in detail.
This assignment is to be directed at an educated audience and you can assume an appropriate level of understanding of the underlying physiological and pharmacological concepts. For example, you would not need to explain the concept of the baroreflex if discussing implications to blood pressure regulation. Nor would you need to explain first-pass metabolism if this was relevant to your topic.
Required Aspects
• Abstract (no more than 250 words – does not contribute to the 1500 word limit)
o You can use your earlier (and revised) rationale to address this aspect
• Introduction
o Provides background relevant to the hypothesis and establishes the rationale for the review
o Should end with your specific hypothesis
• Main body of text that explores the related physiology and pharmacology
o May be broken up using appropriate sub-headings
o Use of sub-headings should not be excessive
• Summary discussion and overall conclusion
• References
o Relevant literature cited throughout the review (at least 15 relevant articles)

In addition to the text and general information, figures, tables and diagrams can be very important tools to convey complex information to your audience. You are welcome – and encouraged – to utilise appropriate illustrations to SUPPORT your text. Just remember that your text must refer to your figures/illustrations, and any figures or illustrations must also have a figure legend and be appropriately referenced.
Formatting Guidelines
Ensure your review is constructed according to the guidelines specified:
• Title page, with title, student number and word count (excluding references)
• Font size 12pt (e.g. Arial or Calibri)
• 1.5 line spacing
• Standard/normal margins (2.54cm)
• Submitted file must be in word format
• Name your file in the format: SURNAME _ID#.docx
Word limit: 1500 words +/- 10% (excluding references).
References
You should refer to existing research publications throughout your report to support your background, ideas and arguments. You will need to include at least 15 peer-reviewed articles, which includes no more than three review articles (and strictly no websites, lay articles or textbooks).
You should focus on the current state-of-knowledge, so the articles used as references in your report should be recent, and ideally published in the past 5 years. In some instances, older articles may also be relevant and appropriate to use, but these should be limited in number.
Begin your search for scientific articles specifically the PubMed database and/or Web of Science.
The citation style to be used is Harvard AGPS. Using a citation manager like Endnote is recommended and will make adding your in-text citations, and constructing the final reference list, in a consistent and correct style much easier.
Student Academic Integrity Policy requires that any work submitted for assessment is the student’s own original work, and as such, the use of ChatGPT and other similar tools CANNOT be used in the writing or drafting of any work submitted for assessment, and AI tools use will incur significant penalties.

Assessment Submission
• Your assignment must include a title page with your name, student number, word count, and title
• You will submit your report via the assignment portal on StudyDesk. This will initially be set as a ‘draft’ so that you can update it as necessary before the final due date/time.
• Submission of your file while it is a draft will generate a Turnitin report. You will be able to resubmit prior to the due date if your originality report/index shows problems with your text.
• It is important to check your Turnitin report and revise text as necessary.
o NOTE: If resubmitting, please remember to allow up to 24 hours for subsequent Turnitin reports to be generated (i.e. after the first report it will take 24 hours for the next one to be generated).
• Please note that plagiarism (including self-plagiarism) constitutes Academic Misconduct and penalties will be imposed .

Marking Criteria
Section Marking Criteria Marks (total 40)
Worth 20% of overall grade
Title The title relevant to the hypothesis and theme of the
review. 3
Abstract Maximum of 250 words.
Concisely summarised the entire review.
Included a brief introduction, body, and conclusion. 3
Introduction Provided a brief initial background and rational which justified the review.
(Why this theme and hypothesis?)
Concluded with a relevant hypothesis that is correctly posed, which integrates at least two lecture themes.
6
Main body text Examined and presented the current state-of- knowledge for the topic.
Presented a logical and flowing argument that explored the hypothesis.
All material discussed was relevant and in context with the topic/hypothesis.
The information presented throughout is correct and current.
Appropriate references are used throughout.
15
Conclusion Presented a concise summation of the report. Included a concluding statement that directly related
back to the hypothesis. 4
Format and Literacy Spelling and grammar were correct throughout. The review was within the allocated word limit of
1500 words, excluding abstract, references, and figure legends.
The text conformed to the required formatting guidelines.
Subheadings were used appropriately and effectively.
4
References Contained relevant research journal articles from the past 5 years.
Preference to primary (original) journal articles over review articles.
No more than 3 review articles were used.
No websites, lay articles or textbooks were used.
Included a minimum of 15 articles.
Reference and citation style were used consistently and accurately with the required Harvard format.

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