Preventing muscle loss in microgravity conditions

Our paper entitled, ''Mitigating sarcoplasmic reticulum stress limits disuse-induced muscle loss in hindlimb unloaded mice'' recently published in the NPJ Microgravity journal unravels the therapeutic potential of a drug to prevent muscle loss in microgravity conditions.

Why did you conduct this investigation?  Skeletal muscle works on the fundamental principle of ‘’Use it or Lose it’’. Conditions such as spaceflight or prolonged bed rest cause loss of muscle mass due to disuse termed, disuse muscle atrophy. This can cause long-term systemic complications and significantly hinder manned space missions. Exercise may be a therapeutic intervention to disuse muscle atrophy but is time-consuming and may show poor compliance and/or efficacy in space. Unfortunately, no drug therapy exists to offset disuse muscle atrophy in microgravity conditions. As a muscle physiologist interested in muscle adaptation, I conceptualized this project by investigating the potential contribution of elevated endoplasmic reticulum (ER) stress to muscle loss in microgravity conditions in a hindlimb unloaded (HU) mouse model. An enthusiastic team of co-workers, including Muhammad Tehsil, Gopika, and Zeinab, ensured the provision of quality data promptly, while Dr Amir helped interpret the transcriptome data. Our study differs from the others as we used a drug to suppress ER stress in HU mice and conducted a global analysis of muscle transcriptome and molecular alterations during spaceflight conditions.  

What is the backstage of this investigation? This work stems from my long-term interest in disuse muscle atrophy due to conditions such as physical inactivity, ageing, and congenital diseases. I have recently developed an interest in investigating molecular targets for pharmacological interventions for muscle loss. After moving to the University of Sharjah, I built a collaboration with Dr Amir, who has expertise in the transcriptomic and proteomic analysis of cells and tissues. Together, we reviewed the literature and found out that the potential contribution of elevated ER stress to disuse muscle atrophy in HU mice is not well understood.

Why is the work important? Maintaining skeletal muscle mass and strength is paramount for human-crewed space missions. Therefore, our efforts to an elevated ER stress contributes to muscle loss in microgravity conditions will be critical in unravelling novel molecular targets to mitigate muscle loss for astronauts in space.

 What’s next? We aim to analyse the protein expression profiles of the three conditions to complement our transcriptomic data. The analysis will give us more insight than the transcriptomic analysis. With the current transcriptomic data, we are using protein-protein interaction and machine learning to identify novel molecular networks that may preserve skeletal muscle mass and/or strength under spaceflight conditions. Our long-term goal is to develop drug therapies that preserve and/or boost skeletal muscle mass and strength in microgravity conditions.