Title: Development of the UK study for the ESA FLUMIAS project: Mitochondrial hydrogen peroxide as a mediator of muscle loss
Funder: UK Space Agency

Abstract: Astronauts rapidly lose skeletal muscle when they are exposed to microgravity and there is some evidence that this loss of muscle is an accelerated form of the slow loss that occurs as we all age. This is known to contribute to frailty, weakness and lack of independence in the elderly. The processes underlying the loss of muscle are not completely understood, but there is evidence that disruption of the parts of the muscle cell that generate energy (the mitochondria) with increased generation of highly reactive molecules, called reactive oxygen species (ROS) play a role in both situations. The most important ROS is hydrogen peroxide which has been notoriously difficult to measure in muscle, but new microscopy techniques have been developed which now allow this. These techniques use special proteins that light up (fluoresce) when they react with hydrogen peroxide, but it has not been possible to use these to study the effects of space flight because fluorescence from cells could not be properly measured on the International Space Station (ISS). The European Space Agency (ESA) have recently worked with the German Aerospace Centre (DLR) to develop a high-quality fluorescent microscope which will be installed on the ISS in 2023 and will be suitable for these studies. In May 2020, the Liverpool-based research group secured ESA support through the SciSpacE programme to undertake a study on the ISS to exploit this new state-of-the-art fluorescent microscope to conduct new imaging studies to examine changes in mitochondrial hydrogen peroxide generation and structure in muscle cells transported to the ISS. The data obtained will allow us compare the changes that occur in microgravity with those that occur during ageing on earth. This proposal was evaluated by ESA in an international competition and received an overall score of 95 out of 100 and was the highest rated application. ESA will therefore cover the costs of the mission to the ISS, but the ESA award does not cover the costs of the essential preparatory and comparative studies that will be required in the Liverpool laboratory. The overarching objective of this application is to obtain support from the UK Space Agency for essential ground-based developments at the University of Liverpool, to perform comparative ground-based reference experiments using the FLUMIAS-ISS microscope at the German Aerospace Space Microgravity User Support Center (MUSC) in Cologne and to support the launch from the Kennedy Space Center in the USA. The funding will also facilitate the extensive testing and approval of the hardware and experiment to allow it to be flown on the ISS in a manned space mission. We will undertake public engagement activities to publicise these UK studies on the ISS and engage post-graduate engineering students in this development work. We will also work with some space industry focussed groups to develop links with relevant UK industry. Completion of this phase of the work will allow this UK study to launch to the ISS in mid-late 2024 where we will address important scientific questions in understanding the mechanisms underlying loss of muscle mass and strength due to ageing and space travel. The data obtained will be crucial in the logical development of targeted interventions to maintain skeletal muscle function in astronauts and elderly people.

Lay abstract: Astronauts rapidly lose skeletal muscle when they are exposed to microgravity and there is some evidence that this loss of muscle is an accelerated form of the slow loss that occurs as we all age. This is known to contribute to frailty, weakness and lack of independence in the elderly. The processes underlying the loss of muscle are not completely understood, but there is evidence that disruption of the parts of the muscle cell that generate energy (the mitochondria) with increased generation of highly reactive molecules, called reactive oxygen species (ROS) play a role in both situations. The most important ROS is hydrogen peroxide which has been notoriously difficult to measure in muscle, but new microscopy techniques have been developed which now allow this. These techniques use special proteins that light up (fluoresce) when they react with hydrogen peroxide, but it has not been possible to use these to study the effects of space flight because fluorescence from cells could not be properly measured on the International Space Station (ISS). The European Space Agency (ESA) have recently worked with the German Aerospace Centre (DLR) to develop a high-quality fluorescent microscope which will be installed on the ISS in 2023 and will be suitable for these studies. In May 2020, the Liverpool-based research group secured ESA support through the SciSpacE programme to undertake a study on the ISS to exploit this new state-of-the-art fluorescent microscope to conduct new imaging studies to examine changes in mitochondrial hydrogen peroxide generation and structure in muscle cells transported to the ISS. The data obtained will allow us compare the changes that occur in microgravity with those that occur during ageing on earth. This proposal was evaluated by ESA in an international competition and received an overall score of 95 out of 100 and was the highest rated application. ESA will therefore cover the costs of the mission to the ISS, but the ESA award does not cover the costs of the essential preparatory and comparative studies that will be required in the Liverpool laboratory. The overarching objective of this application is to obtain support from the UK Space Agency for essential ground-based developments at the University of Liverpool, to perform comparative ground-based reference experiments using the FLUMIAS-ISS microscope at the German Aerospace Space Microgravity User Support Center (MUSC) in Cologne and to support the launch from the Kennedy Space Center in the USA. The funding will also facilitate the extensive testing and approval of the hardware and experiment to allow it to be flown on the ISS in a manned space mission. We will undertake public engagement activities to publicise these UK studies on the ISS and engage post-graduate engineering students in this development work. We will also work with some space industry focussed groups to develop links with relevant UK industry. Completion of this phase of the work will allow this UK study to launch to the ISS in mid-late 2024 where we will address important scientific questions in understanding the mechanisms underlying loss of muscle mass and strength due to ageing and space travel. The data obtained will be crucial in the logical development of targeted interventions to maintain skeletal muscle function in astronauts and elderly people.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL