Microgravity accelerates skeletal muscle degeneration and recapitulates key features of aging, yet the molecular mechanisms underlying age-dependent muscle adaptation remain incompletely understood. Using 3D bioengineered human skeletal muscle tissue chips derived from young and older adult donors flown in an autonomous Lab-on-chip payload on the SpaceX CRS-25 mission to the International Space Station, we investigated functional, transcriptomic, and extracellular vesicle (EV)–mediated responses to microgravity.
Young donor-derived myobundles, particularly under electrical stimulation, exhibited enhanced mitochondrial and oxidative signaling, whereas older tissues showed signatures of mitochondrial dysfunction and inflammation. EVs isolated from conditioned media reflected these age- and environment-dependent molecular states, identifying spaceflight-specific transcriptomic signatures associated with cellular stress and adaptation.
Dr. Siobhan Malany,
University of Florida
Finally, exploratory evaluation of the anabolic compound tomatidine in aged muscle contexts suggests potential modulation of stress and mitochondrial pathways. Together, these findings demonstrate that muscle-derived EVs serve as non-invasive biomarkers of muscle aging and microgravity-induced stress, and that electrical stimulation and pharmacologic interventions may represent viable countermeasures to muscle degeneration during spaceflight and aging on Earth.
The Malany lab focuses on developing muscle physiological countermeasures through advanced modeling systems, including microphysiological platforms and vascularized organoid systems targeting muscle wasting diseases that are performed on Earth and on the International Space Station. The Lab also focuses on developing innovative small-molecule modulators targeting cardiovascular receptor signaling for resistant hypertension. By integrating drug discovery, tissue engineering, and space-biology, the lab seeks to transform treatment strategies for chronic and rare muscle-related diseases.
Dr. Siobhan Malany is a drug discovery pharmacologist and space researcher. She has launched five payloads to the ISS since 2014 and studies microgravity’s impact on human muscle biology using “tissue chips” as models of musculoskeletal disease. As an associate professor at the University of Florida, she directs the In-Space Biomanufacturing Innovation Hub, leading cross-collaborative research focused on cell and tissue-based products for both in-space and Earth-based commercial applications. More recently, she has taken on the role of center director for the strategic planning of the Center for Science, Technology and Advanced Research in Space, an industry-university cooperative research center focused on in-space manufacturing.
Dr. Malany earned her Ph.D. in chemistry from the University of Iowa, completed postdoctoral training in pharmacology at UC San Diego, and was an Alexander von Humboldt Fellow at the Max Planck Institute in Germany. She began her career in the San Diego biotech industry before moving to Florida in 2011, where a visit to see the final Endeavour launch sparked her passion for space research. She is also part of the Central Florida Cluster Initiative and has been featured on NASA’s Houston, We Have a Podcast, Radio Cade, and other media outlets.”