Human brain cells survived for years in a petri dish — and continued to develop on schedule

An even more unusual result was obtained when the researchers mixed cells of different ‘ages’. The older cells, when placed amongst the younger ones, did not start their development from scratch. It was as if they ‘remembered’ the stages they had already gone through, and within just two weeks began producing cells that, in a normal culture, would only appear months later. Scientists refer to this as a kind of cellular memory of time — but this is not a matter of memories or consciousness.

This is not a real brain, but a simplified model of one

The researchers worked with so-called brain organoids.

These are small three-dimensional structures grown from human pluripotent stem cells. Under certain conditions, the cells spontaneously form structures and cell types resembling certain elements of a developing brain.

In this case, the scientists created cortical organoids that simulate the development of the cerebral cortex.

Such structures cannot be described as fully-fledged ‘mini-brains’. They lack a body, sensory organs, a fully-developed vascular system and the entire complex architecture of the human brain. They do not receive normal sensory input and do not replicate the brain in its entirety.

But it is precisely this simplicity that allows researchers to observe the development of human nerve cells under conditions that cannot be replicated directly in a human being.

Such organoids are usually studied for several months

The problem is that the human brain develops extremely slowly.

Many stages of its maturation continue after birth, and it takes nearly two decades to reach adulthood. Mice and other laboratory animals develop much more rapidly, so they cannot fully replicate the human-specific pace of nervous system development.

Brain organoids could solve part of this problem, but until now, most studies have lasted only weeks or months.

Previous work, cited by the authors of the new study, maintained organoids in culture for up to 694 days — just under two years.

The team led by Professor Paola Arlotta has managed to significantly extend this timeframe.

In the new study, cortical organoids were cultured for more than five years.

For a detailed analysis, the researchers collected data on 110 individual organoids.

The new phase of the experiment involved 34 organoids aged between six months and five years. Their data were combined with earlier samples aged between 15 days and six months.

In total, using single-cell RNA sequencing, the scientists analysed 424,720 cells.

This made it possible to track which genes are switched on and off as different types of nerve cells spend months and years in the laboratory.

The picture turned out to be surprisingly orderly.

The cells continued to mature even outside the human body

The organoids did not simply remain alive.

Year after year, their cells underwent changes in gene expression similar to those that accompany the development of the human brain.

Moreover, different cell types matured along their own characteristic trajectories. Older organoids gradually acquired the molecular hallmarks characteristic of later — including postnatal — stages of brain development.

This suggests that a significant part of the ‘timeline’ for the development of nervous tissue may be encoded directly within the cells themselves.

They do not necessarily have to be inside a developing foetus for certain programmes to continue running for years.

The cells were found to have an internal ‘clock’

To check whether the cellular changes really correspond to the passage of time, the team examined another indicator: DNA methylation.

Methylation consists of chemical marks on DNA, the pattern of which gradually changes over the course of a lifetime. Based on these changes, scientists create what are known as epigenetic clocks, which allow them to estimate the biological age of tissues.

In the organoids, the age calculated from these molecular markers corresponded well with the actual time they had spent in the laboratory. Furthermore, the changes resembled the ageing processes observed in real human brain tissue.

This is precisely why the authors state that organoids are capable of ‘recording the passage of time’.

But this does not mean that a small cluster of cells somehow ‘feels’ the passing of years.

The ‘recording’ takes place at the level of the cells’ molecular state.

The strangest experiment began by mixing young and old cells

To find out whether cells really do retain information about their past, the researchers conducted an experiment with chimeric organoids.

They took neural progenitor cells of different ages and placed them in a common, youthful environment.

The logical question was this: if an old cell is returned to an environment of very young cells, will it start its development all over again?

The answer turned out to be no.

The young cells continued to progress through the early stages of development.

The older cells, however, behaved differently under the same conditions.

The older cells refused to start from scratch

Progenitor cells that had already spent around 9–12 months in the organoids retained the ability to produce neurons again.

However, they did not revert to early types of nerve cells.

Instead, in just about two weeks, they began to form later types of neurons, the emergence of which normally takes more than two months.

In other words, the new environment did not erase the cell’s history.

The authors describe this as the ability to ‘remember’ stages already passed through: it was as if the cell knew that it no longer needed to repeat certain stages of development.

It is precisely this aspect of the research that gave the study its unusual title — organoids not only record the passage of time, but also retain a ‘memory’ of their own development.

This is not memory in the human sense

The word ‘memory’ can easily be misunderstood here.

Cells do not remember events, people or what happened to them a month ago.

We are talking about ‘developmental memory’.

Previous changes in gene expression and epigenetic organisation leave the cell in a specific state. Therefore, when environmental conditions change, it does not become biologically ‘newborn’.

The past remains recorded in its molecular programme.

This is fundamentally different from the memory provided by the human nervous system.

The organoids maintained living neurons for years

Another technical challenge in long-term experiments was the survival of neurons.

As the cultures aged, some of the nerve cells were gradually lost. The researchers had to optimise the culture conditions to keep the excitatory neurons alive for considerably longer than had previously been possible.

As a result, the organoids were able to maintain different cell types and continue their development over the course of several years. It was this that enabled scientists, for the first time, to obtain a detailed molecular picture of such a long period of human nervous tissue development outside the body.

Harvard describes the result as a new record for the long-term cultivation of human brain organoids.

Why grow brain cells for five years?

The main aim of such research is not to create an artificial human brain.

Scientists need a model of those developmental stages that are virtually impossible to observe experimentally in humans.

The period following birth is particularly complex. It is clearly impossible to obtain samples of healthy paediatric brain tissue at different stages of development, and animal models do not fully replicate the slow rate of maturation of human neurons.

An organoid that develops over several years rather than a few months opens up the possibility of observing processes that were previously almost inaccessible to laboratory experimentation.

In the future, such systems could be used to investigate how changes associated with various neurological and psychiatric conditions arise during development.

However, the new study does not directly prove anything about autism, schizophrenia or other disorders. Above all, it creates a model that can be used to investigate such questions.

Can the development of brain cells be accelerated?

The experiment involving the mixing of old and young cells offers another interesting possibility.

If scientists learn to control the internal clock of cells, certain stages of development – which currently take months or years – could, in theory, be achieved much more quickly.

In the chimera experiment, old cells have already demonstrated that they are capable of rapidly progressing to later stages if they have previously completed the earlier stages.

For now, this is a fundamental observation rather than a ready-made technology for the accelerated cultivation of human nervous tissue.

However, it demonstrates that the biological timing of cells is not determined solely by their external environment.

Is it possible to grow such organoids for decades?

The new study does not yet provide an answer.

The detailed time series published in *Nature* covers the development of organoids for up to five years, whilst the researchers themselves were able to maintain the cultures for more than five years.

No one yet knows how long such tissue is theoretically capable of surviving with constant support.

An organoid does not have an organism that ages as a whole, falls ill and ultimately dies. On the other hand, an artificial culture has its own limitations: nutrient supply, the accumulation of damage and the ability of individual cell types to survive for long periods.

Therefore, the question of the maximum lifespan of such systems remains open for now.

But scientists have not yet created a ‘brain in a dish’

This is particularly important in light of the sensational result.

An organoid is a model of specific aspects of cortical development, not a miniature replica of the human brain.

It does not possess the full structure of the brain, has no proper connection to the body or the sensory organs, and does not receive the flow of information that shapes a real brain after birth.

The authors of the study also note that future models must take into account the influence of sensory activity and other tissues in the body on the development of the nervous system.

Therefore, the findings are far more interesting without fantastical interpretations: even isolated human nerve cells are capable of following a surprisingly long-lasting internal developmental programme for years and retaining a molecular record of the time that has already passed.

Source

Study:“Human brain organoids record the passage of time over multiple years”.

Authors: Irene Faravelli, Noelia Antón-Bolaños, Anqi Wei and co-authors; senior author – Paola Arlotta.

Journal: Nature, 2026.