Objective

The Cerebral Ageing experiment, supported by CNES and ESA, pioneers the study of human neural organoids cultured aboard the ISS. This first-of-its-kind experiment combines advanced molecular analyses of 3D models of early cerebral development, to explore how spaceflight impacts brain tissue and neural ageing. Its two main goals are: i) to establish space-compatible conditions for organoid culture and enable molecular monitoring of brain tissue changes during long-term spaceflights; ii) to assess whether spaceflight affects neural ageing, with implications for brain function and neurodegenerative diseases.

Methods

We successfully cultured neural organoids (NOs) derived from both a normally ageing individual and a patient with accelerated ageing on the International Space Station (ISS). For the first time on the ISS, regular media changes were performed, over a period exceeding four weeks, mirroring terrestrial culture protocols, and supporting sustained maintenance, growth, and development of organoids. This was enabled by BioServe-designed devices upgraded to our culture specific needs. NOs were fixed at several time points during the mission. Importantly, a subset of neural organoids was maintained alive for return to Earth, allowing post-flight analysis of the persistence of spaceflight-induced alterations. Parallel control experiments were conducted with NOs on Earth.

Results

Results show that our ISS culture conditions successful supported NOs growth and maintenance, matching terrestrial standards. Ongoing immunofluorescence analyses are revealing cytoarchitectural features and neurodevelopmental markers, offering key insights into structural changes associated with NOs in microgravity. Transcriptomic profiling is uncovering space-induced gene expression shifts, and the collected samples are also ready for metabolomic and epigenomic studies to further dissect ageing-related pathways and regulatory changes.

Conclusion

The Cerebral Ageing mission offers a unique window into the study of human neural development and ageing in Space. By integrating transcriptomics, immunofluorescence, and multi-omics analyses, our research provides a comprehensive model to explore molecular mechanisms underlying Space-related alterations with implications for cerebral ageing. These results could have far-reaching implications for neurodegenerative disease research, space exploration, and future therapies. We will present the findings obtained to date.