The ageing brain

"We know a great deal about how age affects brain function, but we know virtually nothing about the underlying molecular mechanisms," says Johan Jakobsson.

He is Professor of Neuroscience at Lund University and devotes much of his research to studying brain ageing in relation to neurodegenerative diseases. But why do we know so little about something so important? Johan Jakobsson explains that there are many methodological challenges.

"All the brain tissue we work with comes from deceased individuals; it is not possible to take biopsies from the brains of living people. This means that we largely lack material from young, healthy individuals. No young person dies in full health. Young people usually die as a result of trauma following accidents or suicide, which may have affected their brains."

There is also a lack of good model systems for studying the mechanisms behind cellular ageing in the laboratory, and results from experiments carried out in mice and rats are difficult to translate to humans, according to Johan Jakobsson.

Anyone who has ever been to a school reunion realises that people age at different rates.

Biological age

Anyone who has ever been to a school reunion realises that people age at different rates. While chronological age shows how much time has passed since we were born, biological age is more a measure of how well the body is functioning. Genetics in combination with lifestyle influence whether the biological clock ticks faster or more slowly than the chronological one.

Biological age can be measured in different ways, often as a combination of biomarkers and physical and epigenetic tests. The latter are central to studying what happens at the cellular level and are based on analyses of methylation patterns on the DNA molecule (see fact box).

DNA is obtained from blood samples, which are easy to collect and usually provide a good overall picture of a person’s biological age. However, they do not provide detailed information about what is happening specifically in the brain’s cells or how the brain is affected by age.

The brain is somewhat unusual. Unlike, for example, skin or blood cells, which are constantly renewed, there is very limited generation of new nerve cells in the brain, although research has shown that some new neurons can still form in areas such as the hippocampus. But broadly speaking, the nerve cells we are born with are largely the ones we retain for the rest of our lives.

"The fact that they are not renewed may make them particularly vulnerable to several age-related diseases that affect the brain. Otherwise, why would Parkinson’s, Alzheimer’s or Huntington’s disease affect the brain specifically rather than other organs?"

For example, Huntington’s disease is caused by a misfolded protein, huntingtin, which is produced in all the body’s cells but primarily affects the brain.Johan Jakobsson’s research is about studying ageing in relation to neurodegenerative diseases. His research group works on mapping epigenetic changes by studying methylation patterns and how they change with age and in different diseases.

Inflammageing

Another issue that interests Johan Jakobsson is “inflammageing”, from the English words inflammation and ageing – a low-grade chronic inflammation that increases with age. It is known that disease can accelerate inflammation and that Parkinson’s and Alzheimer’s disease have a clear inflammatory component.

"But we do not know why it begins, why it is chronic, or how it affects the brain and ageing."

Johan Jakobsson continues:

"Our long-term aim is to be able to identify more precisely what constitutes healthy ageing, what constitutes disease-related ageing, and how the two differ. If we understand the mechanisms, we may be able to slow disease-specific ageing."

Text: Eva Bartonek Roxå
Foto: Johan Persson
The article was previously published in the journal Vetenskap & Hälsa, 2026.