Breaking Longevity Record
Harvard neuroscientists have set a record for keeping lab-grown human brain organoids alive, sustaining the peppercorn-sized clumps of cells for more than five years — and in some cases for seven. The previous record for the oldest organoid was 694 days, set in 2021 by a team at UCLA and Stanford. The new study, published in the journal Nature, describes how the organoids continued to change and mature over the years, even though they never developed inside a body. As Paola Arlotta, the senior author and a Harvard professor, told AFP, "The brain can continue to develop outside the context of a person for this unprecedented amount of time."
What Are Organoids?
Organoids are tiny clumps of neural tissue grown from stem cells. They mimic the earliest stages of brain development and are used by scientists to study the brain's mysteries and test new medicines without using animals. Typically, these organoids live only a few months, offering a window into the initial phases of brain development, which in humans takes nearly two decades. The Harvard team's achievement extends that window dramatically. Each organoid contains more than one million cerebral cortex cells derived from human donors, as reported by FAS Current.
Aging Like Real Brains
The study found that the organoids aged in ways similar to real brains. According to FAS Current, the organoids "recorded the passage of time and retain a memory of the developmental steps already performed." The researchers used three genetic "clocks" to analyze aging, including DNA methylation, which acts as an "age clock" to estimate biological age. The organoids showed changes in gene activity, cell types, and DNA methylation over the years. Madeline Lancaster, a developmental biologist at the University of Cambridge who commented on the study, said the organoids showed signs of maturation and aging like an actual brain, as reported by Scientific American. The organoids lacked blood vessels and sensory input, which Arlotta noted as limitations.
Time Warp Experiment
In a striking experiment, the researchers created a "chimera" by mixing cells that had been developing for a year with cells that were only two weeks old. As reported by Phys.org, the older cells "jumped ahead" and began producing neurons that normally take around four months to develop. This "time warp" effect suggests that the organoids retain a memory of their developmental history, allowing them to accelerate when exposed to younger cells. Arlotta emphasized that this does not mean the organoids have memories in the human sense, but rather that their past is "engraved" on a cellular level.
Behind the Scenes
STAT offered a personal glimpse into the research. Irene Faravelli, a junior scientist in Arlotta's lab, walked into Arlotta's office two years ago with images of old brain organoids. When Arlotta asked if she had analyzed them, Faravelli worried she had made a mistake. Arlotta reassured her, saying, "I was actually pleased that somebody had the courage to do this." The study was spearheaded by Faravelli and Noelia Antón-Bolaños, according to Scientific American. The team examined 34 organoids with single-cell RNA sequencing at eight timepoints and combined data on 110 organoids and nearly 425,000 individual cells, as reported by FAS Current. They also refined techniques to improve neuron survival, including a liquid medium and amino acid supplement. The organoids were destroyed at the end of the experiment, as noted by Phys.org.
Ethical Considerations
Scientific American raised bioethical concerns, including the possibility that the organoids might feel pain. Arlotta responded that it is "highly, highly, highly unlikely" that the organoids are even faintly conscious. She stressed that organoids are "biological models" or "avatars" that are far less complex than real brains and do not receive sensory input.
Future Implications
The ability to keep organoids alive for years opens new avenues for studying adult-onset disorders such as schizophrenia, Alzheimer's, and Parkinson's disease, as noted by Scientific American. By allowing brain tissue to mature over longer periods, researchers can investigate how these diseases emerge and progress later in life. The study received NIH funding, as reported by FAS Current. The Harvard lab now has organoids that are seven years old, and the team continues to push the boundaries of what is possible in stem cell research.