08/19/2026
"In this new study, Arlotta and colleagues tested their organoids’ ability to survive and continue to develop over an extended period. During periods in which organoids survived for nearly six years, the researchers tracked the gene expression, biological age, as indicated by chemical alterations to the genome, and structure of organoid cells and with single-cell resolution.
"They detected the emergence and maturation of neurons as well as their supporting glial cells, with many milestones, including signatures of postnatal development, occurring in the same cadence they would naturally in the human brain. Biological age clocks, which are models trained on real-world human data, demonstrated that their molecular and chronological ages matched, signifying that the organoids developed at a slow, realistic pace, despite being grown outside the context of the body.
"Neurons also exhibited functional maturity by establishing connections between each other and firing electrical signals that the organoids sustained for at least two years. The authors specifically grew tissue in a fluid that supported this activity, which they suspect was key to their organoids’ neuronal longevity.
"'The brain doesn’t develop in a vacuum. It’s an organ of incredible complexity that interacts with so many other systems. It was not a given at all that our simplified model would match natural development in this many ways,' said co-first author Irene Faravelli, M.D., Ph.D., who conducted this work as a post-doctoral research fellow at Harvard.
"To be more certain that what they were seeing was not just circumstantial, the authors transferred neurons from older to younger organoids and then gauged their response to the new environment. Despite receiving signals telling them otherwise, the older cells continued progressing as if they were still housed in their prior organoids, skipping developmental steps compared to their younger neighbors.
"'I like to think of this as a sort of ‘warping of developmental time’ indicating that the organoid cells record and recall the time they have already spent in culture. This suggests their development is driven by a cell-intrinsic clock, reflecting mechanisms of endogenous human brain development,' said Arlotta.
"The findings expand on what scientists previously thought was possible for organoids to accomplish and, moving forward, the authors intend to continue pushing the boundaries. Future research could build on this study by aiming to add anatomical complexity to these organoids, simulating developmental disorders, or testing experimental interventions."
https://www.nih.gov/news-events/news-releases/brain-organoid-maturation-driven-lifelike-developmental-clock National Institutes of Health (NIH)
Researchers sustained the organoids for nearly six years, potentially unlocking longer term studies of neurodevelopmental disorders.
