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Adults whose brains still have strong neuron production seem to have better memory and cognitive function than do those in whom the ability wanes, finds a study published today in Nature. The authors examined brain samples from deceased donors ranging from young adults to ‘super agers’ — people older than 80 with exceptional memory.

They found that young and old adults with healthy cognition generated neurons, a process called neurogenesis, at high levels for their age. The team estimated that the new neurons made up only a small fraction — 0.01% — of those in the hippocampus, a brain region that’s essential for memory. By contrast, in people experiencing cognitive decline, including individuals with Alzheimer’s disease, neurogenesis seems to falter: the researchers spotted fewer developing, or immature, neurons in those brain samples.

Surprisingly, a group of ‘super agers’ had an even higher number of immature neurons than did other groups, and significantly more than did those with Alzheimer’s. However, the group sizes were small, so the findings were not all statistically significant.

Maura Boldrini Dupont, a neuroscientist and psychiatrist at Columbia University in New York City, says that the small size of the groups — each had ten or fewer individuals — is a reason to take the results with a grain of salt.

Understanding the tools that the brain uses to generate neurons and maintain cognitive function in old age could help researchers to develop drugs that induce neurogenesis in people with cognitive decline, says co-author Orly Lazarov, a neuroscientist at the University of Illinois Chicago.

Controversy over neurogenesis

The findings support the idea that people’s brains continue to generate neurons even in adulthood. But that idea hasn’t always been accepted.

In the early 1900s, neuroscientist Santiago Ramón y Cajal suggested that the human brain could not form neurons after birth. Eventually, researchers found that neurogenesis did occur in childhood, but still thought that was the endpoint.

“That’s what they used to teach when I went to medical school,” Dupont says.

In the past few decades, however, this dogma was challenged by new evidence supporting neurogenesis in the adult hippocampus, fuelling an ongoing debate in neurobiology.

Although researchers know that neurogenesis occurs in some adult animals, including mice and primates, they haven’t been able to agree on whether it happens in the brains of human adults. That’s mainly because there are more tools for studying neurogenesis in animals than in humans. In mice, for instance, researchers can inject chemicals that trace the birth and development of neurons. This cannot be done in living people, and research in human brain samples has been limited, Lazarov says.

One tool researchers have used to study neurogenesis in humans, however, is protein markers. Antibodies can be used to detect certain proteins expressed by neural stem cells — which can turn into neurons — and immature neurons in donated brain samples. But Lazarov points out critics’ argument “that these proteins are not specific enough and could be expressed in other cell types, not just in neurogenesis”.

So scientists have turned to single-cell RNA sequencing to find more specific genetic markers of neural stem cells and immature neurons in the human hippocampus.

Into the future

Lazarov and her colleagues went a step further in their latest study. They not only used RNA sequencing to identify the genetic signatures of these cell types, but also uncovered their epigenetic signatures. Epigenetic markers are DNA modifications that control gene expression. The team used an assay that pinpoints parts of a cell’s DNA that are primed for expression to determine these signatures. Dupont says that the assay is a strong point of the study.

Lazarov says that the next step would be to understand the function of the neurons generated in the adult brain. “What we need is functional validation of these cells, to tell what they’re doing in the human brain,” she says, adding that this would require new imaging techniques that are sensitive enough to detect this activity.

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