We may lose hair, muscle and memories with age – but the brain’s cleaning system refuses to slow down. A new study shows that the production of brain fluid remains high throughout life, challenging the persistent theory that the brain gradually loses its ability to clean itself.
The brain is bathed in cerebrospinal fluid. This not only protects the brain from impact but is also the main ingredient in the system that cleanses the brain of waste products.
In fact, humans produce half a litre of cerebrospinal fluid every day. This constant rinsing is essential to prevent waste from building up and disrupting brain function.
Cerebrospinal fluid can be compared to the water in a washing machine. Here, too, water must be added to rinse the dirt off the clothes after the washing cycle.
It has long been suggested that the production of cerebrospinal fluid declines with age and that this may contribute to cognitive decline among older people.
A new study challenges this long-held assumption, showing that cerebrospinal fluid production stays high throughout life – at least in rats.
The study also sheds new light on the mechanisms driving this vital process.
Understanding – and perhaps one day controlling – this production could open new ways to treat currently untreatable brain diseases.
“These experiments showed that cerebrospinal fluid production remains unchanged over time. There was no difference between young and old rats,” explains Nanna MacAulay from the Department of Neuroscience at the University of Copenhagen, Denmark.
The research has been published in Nature Communications.
Human brains remain a closed book
The study aimed to quantify how much the production of cerebrospinal fluid declines with age and why.
The idea was that this would reveal how and by how much production should be increased to protect the brain from neurodegeneration.
Since human cerebrospinal fluid production cannot be measured accurately, and certainly not among healthy humans, the researchers instead studied cerebrospinal fluid production in rats.
The researchers tracked various aspects of cerebrospinal fluid dynamics from when the rats were very young until they were two years old.
A two-year-old rat is roughly equivalent to a human in their seventies – in other words, with a clearly ageing but not fragile brain.
Ageing brains keep the cleaning system running – and the researchers timed the rinse cycle
Cerebrospinal fluid is produced in the choroid plexus – a kind of fine-meshed filter of blood vessels that lie like small fringes in the fluid-filled cavities of the brain.
Here, specialised cells pump salt and water from the blood into the brain, maintaining a constant flow of fresh cerebrospinal fluid.
The researchers measured how rapidly the choroid plexus produces the cerebrospinal fluid and whether this declines with age.
The researchers injected a fluorescent fluid into the rats’ brains and monitored how it became thinner and thinner as it flowed through the cavities.
How quickly the fluorescence disappeared revealed that even old rats produced almost as much new cerebrospinal fluid as young rats – about 0.4 mL per hour.
“These experiments showed that the dynamics of cerebrospinal fluid production remain unchanged over time. The young and old rats did not differ,” says Nanna MacAulay.
Old brain cells work as hard as young ones
The team also examined the cells’ “work manuals” – the genes that instruct them to build the proteins (such as Na⁺/K⁺-ATPase) that pump fluid into the brain.
The theory was that, over time, fewer of the proteins that transport cerebrospinal fluid into the brain would be produced. Defects in these proteins, or lack of them, are suspected to be part of the disease picture in some neurodegenerative diseases.
However, the researchers found no difference between young and old rats in this regard.
Putting the brain’s washing cycle to the test
The researchers found no differences when they examined the cells under an electron microscope. In fact, the cells in young and old brains were so identical that the researchers initially thought they had made a mistake.
Finally, they measured the metabolism in the choroid plexus tissue – the part of the brain that produces cerebrospinal fluid – to determine whether it declined with age. Here, there were no signs that the genes influencing metabolism slowed down with age.
They also measured how much energy the choroid plexus cells used – and here the metabolism was stable, about three times higher than in other fluid-transporting tissues such as the kidneys and intestines, which also move large quantities of fluid.
“Everything suggests that brain fluid production does not decline with age – likely because this function is crucial for keeping the brain working,” notes Nanna MacAulay.
How researchers will find the answer in humans
Although what happens in rats cannot be directly parallelled with what happens in humans, Nanna MacAulay says that imagining similar experiments involving humans is very difficult.
The reason is simple: inserting needles into the brains of healthy people just to extract brain fluid would be ethically indefensible because of too many risks.
However, researchers are working on developing methods that will enable them to measure the production of human brain fluid non-invasively using magnetic resonance imaging.
“We are looking into this now so that we can investigate whether cerebrospinal fluid production declines among people with cognitive decline,” says Nanna MacAulay.
Will we one day be able to control the flow of fluid in the brain?
According to Nanna MacAulay, there are many interesting perspectives in learning more about the production of cerebrospinal fluid and how disease can alter its production.
For example, some diseases disrupt the dynamics of cerebrospinal fluid, which can result in hydrocephalus (water on the brain).
This condition can arise as a result of a congenital defect, after a brain haemorrhage or as normal-pressure hydrocephalus, which for unknown reasons affects up to 2% of older people.
“Therefore, some people’s health can improve if we can figure out how to reduce the production of cerebrospinal fluid. But in principle, the same mechanisms can also be adjusted to produce more cerebrospinal fluid if, for example, it turns out that this is part of the clinical picture among older people with cognitive decline,” concludes Nanna MacAulay.
