A NIH-funded team has shown that 3D cell culture models of human brain tissue (organoids) can be sustained for nearly six years, mimicking later stages of human brain development. During this period, researchers tracked gene expression, biological age (via chemical alterations to the genome), and cellular structure at single-cell resolution. They observed the emergence and maturation of neurons and glial cells, with many developmental milestones occurring at the same pace as in the natural human brain. Biological age clocks confirmed that the organoids’ molecular and chronological ages matched. Neurons also established functional connections and fired electrical signals for at least two years. The key insight is that the organoids developed at a slow, realistic pace despite being grown outside the body, suggesting a cell-intrinsic developmental clock. This breakthrough could enable long-term, benchtop studies of neurodevelopmental disorders like autism.
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