Major demographic changes are affecting UK and other societies leading to rapidly increasing numbers of older people with relatively poor health and quality of life.
It is estimated that by 2034, 23% of the UK population - estimated to be around 15 million people - will be over 65 years of age. Physical frailty is a major factor affecting the ability of individuals to maintain independence and is primarily due to age-related loss of skeletal muscle mass and function (known as sarcopenia).
The mechanisms underlying age-related loss of muscle have not been fully evaluated, but we have demonstrated that muscle from ageing animals and humans show attenuated adaptions to exercise that compromises their ability to maintain muscle mass and function.
So where does the International Space Station factor into this?
Astronauts and animals exposed to microgravity also lose skeletal muscle mass and, although astronauts routinely undertake aerobic and resistance exercise in space to help ameliorate muscle loss - in an analogous way to muscles of older people, this is only partially successful since the muscle responses to exercise are also attenuated in microgravity.
Our hypothesis is that an analogous failure of muscle adaptations to contractile activity occur in both ageing and in muscle exposed to microgravity and that by studying the way that muscle responds to repeated contractions in microgravity we will gain further understanding of the way that muscle fails to respond to exercise in older people and in astronauts in space.
Modifying loss of muscle mass
The muscle research group at the University of Liverpool's Institute of Ageing and Chronic Disease, have evaluated key mechanisms underlying adaptations of skeletal muscle to exercise.
We demonstrated that exercising muscle of young or adult animals and humans generates reactive oxygen species (ROS) that stimulate activation of specific transcription factors which subsequently leads to increased generation of a number of protective and cytoprotective proteins.
Such responses do not occur in muscle from older animals and humans in response to exercise.
Correction of these defects in experimental models can prevent age-related loss of muscle mass and are the basis for drug-development studies that attempt to identify loss of muscle mass in elderly individuals.
We have demonstrated that these attenuated responses of muscle to contractile activity in ageing can also be studied in cell culture models.
This provides the basis for our planned experiments using cultured constructs of skeletal muscle cells on the International Space Station.
Growing muscles in space
We have designed an experimental system to test these questions in studies on the International Space Station. Using a specially designed scaffold, we will support muscle cell cultures to allow them to grow in microgravity.
The experiment begins with a culture of 3D myotube constructs ~7 days prior to launch into space within specially designed experimental containers.
These are arranged in a collagen-based hydrogel contracted around two anchor points in a structure designed by a team from the Institute of Ageing and Chronic Disease.
During the launch, the 3D muscle cultures will be maintained at ambient temperatures at which our pilot studies indicate the constructs will remain viable.
Following successful arrival at the International Space Station, the experimental containers will be stored at room temperature prior to installation in KUBIK - an incubator which is maintained permanently on the ISS (See below for more information on the KUBIK incubator).
We envisage containers will be stored for up to 6 days prior to integration within KUBIK. After 24hrs, cultures would be electrically stimulated to contract. We will then examine responses of the muscles to these contractions.
Kayser Space Ltd
In order to provide the complex hardware that will allow these experiments to be undertaken, the University has partnered with a specialist company, Kayser Space Ltd.
Founded in 1986, Kayser have extensive experience of designing and manufacturing systems to undertake biological experiments in space.
We have jointly established a detailed plan for design, manufacture and testing of this hardware prior to supplying it to the European Space Agency for launch and flight to the ISS. The University of Liverpool and KAyser Space Ltd will jointly support the space mission.
After the design and manufacture of our prototypes, the newly founded Sensor City facility in the Liverpool Knowledge quarter was chosen as the ideal site for testing and further development of our design. With state of the art laboratory facilities, Sensor City - a collaboration between the University of Liverpool and Liverpool John Moores University - is a peerless scientific and collaboratve environment in which we were able to thoroughly run our prototypes through their paces, ensuring that we were able to establish an aparatus that would be capable of performing without fault on the International Space Station.
In November 2021, a team of early career researchers consisting of Dr Samantha Jones, Dr Shahjahan Shigdar and Miss Kay Hemmings from the University, travelled to Florida to begin MicroAge’s six week-long preparatory phase at NASA’s Space Station Processing Facility (SSPF) based at the Kennedy Space Center (KSC).
Unlike conventional research trips, The team were faced with the task of designing a functional, multi-purpose laboratory from scratch. The logistical challenge of shipping specialist equipment and valuable samples ahead of their arrival in the midst of a pandemic, as well as ensuring that the necessary facilities requests were made to NASA’s operational support team was no mean feat.
The team wasted no time putting the new lab through its paces, maintaining 27 flasks of human myocytes, assembling more than 120 3-D printed scaffolds, and fabricating a total of 360 skeletal muscle constructs! The sheer volume of samples produced was required in order to accomodate 3 separate sample integrations, covering 6 launch attempt dates. With steady hands and critical focus, the first integration was performed on the 18th December whereby the Liverpool team and engineers from Kayser Space Ltd filled and sealed 24 individual bioreactors, termed ‘experimental units’ (EUs), before handover to the NASA launch team on the morning of the 19th December ready for flight.
After sample integration the MicroAge team, joined by Professor Malcolm Jackson, Professor Anne McArdle and Dr Chris McArdle were fortunate enough to be given a guided tour of Launch Complex 39. The team were ecstatic to have visited both the Vehicle Assembly Building (VAB) and Pad 39A to see the loaded SpaceX Falcon 9 rocket standing against the gantry before lift-off.
Despite awful weather conditions, the MicroAge experiment was launched at 5.07AM on the 21st December with the SpaceX Cargo Resupply (CRS) Mission 24, with celebrations and cheers from the team, who were watching with anticipation from a viewing point across the river.
Once docked and unloaded onto the ISS, the EUs were inserted into the KUBIK incubator by ESA astronaut Matthias Maurer on 23rd December. The automated experimental timeline that had been meticulously programmed by Kayser Space Ltd, was successfully executed over a 56-hour
period and the EUs cryopreserved.
The hard work is not over for the MicroAge team. Over the coming months, they will be focussing upon multiple analyses of samples, from the ISS, running ground reference experiments and continuing with their public outreach campaign.
A fantastic opportunity for us to investigate if a similar failure occurs in muscle exposed to microgravity, to aid understanding of the underlying mechanisms that affect muscle in the ageing population.Professor Malcolm Jackson
The KUBIK Incubator on the ISS also contains a centrifuge and our experiment will examine the contraction of muscle constructs exposed to microgravity or artificial gravity induced by centrifugation. We will also examine the effects of microgravity on the adaptive response to stimulation in culutres of myotubes that overexpress a particular protein that has previously been shown to rescue the age-related loss of adaption to contraction in mice. On completion of the experiments, the muscle samples and medium in which the muscles are cultured will be preserved and frozen prior to return to earth and analysis in the laboratories in Liverpool.