Research in Space: Expanding Our Understanding of Age-Related Muscle Loss
Keywords: Lentivirus vector, Age-related muscle loss, International Space Station
Aging is not for the faint of heart… or legs, arms, back, etc. While a select few areas of the body continue to regenerate throughout life, skeletal muscle, particularly that in the legs, begins to decline in the 30’s and 40’s. Muscle loss accelerates after 65, presenting challenges in balance and mobility and emphasizing the importance of understanding mechanisms of muscle loss and protection. Because age-related muscle degeneration occurs over many years, scientists at the University of Liverpool have developed an out-of-this-world method to model the phenomenon on a much shorter timescale. 3D muscle constructs, made from cells engineered with VectorBuilder lentivirus, were used to study muscle loss in the microgravity environment of the International Space Station, allowing researchers to elucidate critical mechanisms behind muscle degeneration.
Understanding age-related muscle loss
With age, skeletal muscles lose mass and strength and become less responsive to exercise. This means that, even with proper exercise, older adults may not gain as much muscle mass or strength compared with younger adults. By age 70, skeletal muscles have atrophied and muscle fibres have been lost to such a high degree that the cross-sectional area of muscles is reduced by 25-30% and strength is reduced by 20-40% (Figure 1).
Figure 1. A schematic of muscle loss in aging adults.
A pivotal element in age-related muscle loss appears to be reactive oxygen species (ROS) (particularly but not exclusively H2O2) that are produced during exercise. In younger individuals, ROS activate the production of cytoprotective enzymes and proteins. However, with age, muscles enter a state of chronically increased ROS production and inflammation, which is proposed to diminish the effects of exercise. Another more recently-identified key element for adaptive responses to exercise is Heat Shock Protein 10 (HSP10). This gene is expressed in mitochondria where it acts as a molecular chaperone. Overexpression of HSP10 in transgenic mice has been shown to partly prevent age-related loss of muscle mass and strength, likely by preventing damage induced by the accumulation of oxidized mitochondrial proteins.
Why study muscles in space?
Because age-related muscle degeneration takes decades to manifest, it is difficult to study the mechanisms of its progression and to discover potential interventions to prevent or remedy it. However, astronauts and animals experience muscle loss at very high rates in microgravity. After half a year in microgravity, astronauts can lose up to 30% of their muscle mass, necessitating strict exercise regimens (Figure 2). In microgravity, their muscles also show poor response to aerobic exercise or resistance training compared with adults on Earth. The ISS therefore offers a unique setting to study loss of muscle mass and function on an accelerated timeline.
Figure 2. Astronaut Loral O’Hara exercising in microgravity. Astronauts on the ISS follow a strict workout regimen to prevent muscle atrophy.
The MicroAge I study
The University of Liverpool collaborated with the UK Space Agency and Kayser Space Ltd to explore whether microgravity exposure could serve as a suitable model for age-related muscle loss. The "MicroAge I" project launched in 2021, aiming to investigate the effects of microgravity on muscle loss. The researchers proposed that HSP10 overexpression might protect against the rapid muscle mass loss and exercise unresponsiveness that occur in microgravity.
Muscles the size of a grain of rice were grown on scaffolds using distinct pools of cells: one unaltered control, and one that had been engineered to overexpress HSP10 using a lentivirus provided by VectorBuilder (Figure 3). The VectorBuilder lentiviral vector successfully engineered a population of cells with significantly enhanced expression of the gene of interest; researchers found that HSP10 protein levels were increased 40-fold in transduced cells compared to non-transduced cells.
Then, on the ISS, the muscle constructs received electrical stimulation for contraction to simulate exercise in microgravity and were provided with oxygen and nutrients. After returning to Earth, preserved samples underwent comprehensive testing for:
- Transcriptional responses (RNAseq)
- Changes in the muscle proteome
- Activation of transcription factors (via proteomic and bioinformatics analysis)
- Cytokine release (LuminexTM analysis of culture medium)
The researchers found that exposure to microgravity dramatically affected mitochondria in muscle cells. Genes associated with mitochondrial function were dysregulated; specifically, genes associated with chronic inflammation and a biomarker for mitochondrial dysfunction were upregulated. Furthermore, genes associated with maintenance of muscle mass were downregulated, showing parallels with age-related muscle loss.
Figure 3. Workflow of muscle construct growth. Genetically engineered and wild-type human myoblasts were seeded onto scaffolds in fibrin hydrogel. After assembly, growth, and differentiation, mature constructs capable of contracture upon electrical stimulation formed. Adapted from Jones et al., 2026, npj Microgravity.
Looking ahead
This research will continue in 2026/27 on the ISS in a European Space Agency mission. Muscles transformed by a lentiviral vector system for stable expression of ratiometric hydrogen peroxide probes (HyPer7) will be investigated. HyPer7 probes are used for dynamic measurement of ROS (H2O2) in the cytosol and mitochondria of muscle cells. Therefore, this extended study will offer dynamic insights into the role of ROS signaling in muscle loss during spaceflight and in aging on Earth.
Conclusion
The microgravity environment on the ISS provides a unique opportunity to study muscle loss on an accelerated timescale, but researchers first need to establish whether the biological mechanisms of age-related vs. microgravity-related muscle loss are comparable. The MicroAge I study revealed important information about the validity of microgravity as an accelerated model for age-related muscle loss, and about the specific biological phenomena behind microgravity-related muscle loss.
VectorBuilder’s mission is to equip scientists to perform groundbreaking, lifesaving research. In providing materials for researchers to engineer these cells, we were proud to be a small part of a direct analysis of how a specific protein affects muscle loss in microgravity. This data will help scientists to understand the molecular and cellular causes of age-related muscle degeneration, develop interventions to prevent or alleviate its dangerous effects, and create protocols to keep astronauts healthy in space.
Want to learn more?
Dr. Anne McArdle, one of the co-PIs of the study, recently spoke at VectorBuilder’s Gene Delivery Seminar Series. Check out the full recording here!
References
Doherty, T.J. (2003) Invited review: Aging and sarcopenia. J Appl Physiol. 95:1717–27.
Image references
Gaskill, M.L. (2024) NASA Astronaut Loral O'Hara, Expedition 70 Science Highlights.
