Nuclear bomb tests carried out during the cold war have had an unexpected benefit.
A radioactive carbon isotope expelled by the blasts has been used to date the age of adult human brain cells, providing the first definitive evidence that we generate new brain cells throughout our lives.
The study also provides the first model of the dynamics of the process, showing that the regeneration of neurons does not drop off with age as sharply as expected.
In mammals, most types of brain cell are created at or soon after birth and are never renewed. But studies in rodents and monkeys have shown that in 2 regions new neurons continue to be created even in adulthood – the hippocampus, which is involved in learning and the formation of new memories, and the olfactory bulb, which processes smell.
However, there has been some controversy over whether the same is true for humans. Fifteen years ago a study found evidence for such neurogenesis in adults up to the age of 72 (Nature Medicine, doi.org/b7hjfz), but the research relied on a chemical called bromodeoxyuridine (BrdU) to label neurons. BrdU was used at the time to track the spread of tumours in people with cancer, but it was banned shortly after and so the study was never repeated, leading some researchers to question the results.
Another study on London taxi drivers suggested that the hippocampus grows with increasing knowledge of the city but this, too, has been controversial.
The new study settles the debate. "The existence of adult hippocampal neurogenesis in humans is not arguable this time," says Sandrine Thuret at King's College London, who was not involved in the work.
Instead of chemical labelling, Jonas Frisén at the Karolinska Institute in Stockholm, Sweden, and colleagues used a by-product of the above-ground nuclear bomb tests carried out by the US, UK and Soviet Union between 1945 and 1963. As a result of these detonations, atmospheric levels of the radioactive isotope carbon-14 increased dramatically during this period. It has decreased steadily since.
Carbon-14 enters the food chain and eventually finds its way into our cells, which integrate carbon-14 atoms into their DNA when a parent cell splits into two new daughter cells. The amount of carbon-14 in the atmosphere is therefore mirrored in the cells at the time they are born.
By analysing brain tissue using mass spectrometry equipment, the team was able to measure the number of carbon-14 atoms trapped in different populations of cells in different brain regions.
They could then compare this figure to known data for atmospheric levels of carbon-14 to date the birth of a cell in different people to within about a year. The level of carbon-14 is higher in older cells grown closer to the peak of nuclear bomb testing than in cells born more recently.
Frisén's team previously used this method to show that humans are the only known mammal in which neurogenesis does not occur in the adult olfactory bulb, since the cells in this brain region were the same age.
But looking at the hippocampus in 55 post-mortem brains aged between 19 and 92, the team has now found that a subset of neurons in an area of the hippocampus called the dentate gyrus are indeed created throughout adulthood. In effect, a small population of our brain cells remains permanently young, renewing itself continually. By modelling the process, the team estimated that we generate around 700 new neurons every day. "Everyone working on adult hippocampal neurogenesis is excited about this work," says Thuret.
The team was surprised that the ability to create new neurons appears to stay with humans longer than it does in mice. "In mice the decline is pretty dramatic," says Frisén. But instead of the 10-fold decrease between young and middle-aged mice, the team found only a four-fold decrease in humans, he says.
But the newborn brain cells in humans do not appear to live long. In rodents, the hippocampus gradually gets bigger as new cells are added. "In mice, there is a net increase," says Thuret. But this is not seen in humans – in fact, our hippocampus slowly shrinks. "There are more dying than being born," she says.
The reason for this turnover remains unknown. Many studies in mice show that young neurons are necessary for forming new memories. But this has not been tested in humans.