Epigenetic changes in the developing and aging brain
The Youth-GEMs project aims to understand how genes, brain biology, and life experiences interact to shape young people’s mental health — and how this knowledge can help predict, prevent, and better support those at risk of developing mental ill-health. A major part of this effort involves studying epigenetics: the chemical changes that influence how our genes work without changing the genetic code itself.
In this article, Alice Franklin – a PhD student at the University of Exeter – explains her team’s research into how epigenetic changes affect brain development and aging, and what this can tell us about the origins of certain mental health conditions like autism and schizophrenia.
What are epigenetic changes and how are they linked to brain health?
Our DNA is like an instruction manual for building and maintaining the brain. But these instructions are not all used at once – they’re controlled by epigenetic processes which act like switches, turning genes on or off at the right time and in the right brain cells. One of the most important of these processes is DNA methylation, which helps guide brain cells to develop into the correct specialised types and functions during early development.
Differences in how the brain develops before birth are thought to contribute to conditions such as autism and schizophrenia. “We wanted to understand how epigenetic changes shape brain development, and whether genes linked to these conditions are affected.” Alice explains. “This knowledge could bring us closer to understanding how and why these conditions arise and how to better support people impacted by them.”
What did the study look into?
To do this, the Youth-GEMs team in Exeter studied DNA methylation in the human brain across the entire lifespan – from just 6 weeks after conception to 108 years of age – using nearly 1,000 human brain samples, making it the largest dataset of its kind. Professor Jonathan Mill who leads the Exeter team described their approach. “We measured DNA methylation at over 850,000 points in the genome – checking 850,000 “tiny switches” that can turn genes on or off – to see how these patterns change as the brain develops and ages. We also developed a method to separate neurons from other brain cell types so that we could study them in detail.”
What were the main findings?
The team found that DNA methylation changes most rapidly before birth, reflecting the intense activity needed to build the brain. Some changes were specific to the prenatal period, while others continued through childhood and into adulthood.
They also found that neurons began to show their own unique DNA methylation patterns early on, distinct from other brain cells.
Importantly, genes linked to autism and schizophrenia were more likely to show large changes in DNA methylation during brain development. This suggests these genes play a critical role in how the cortex — the outer layer of the brain responsible for thought, memory, and emotion — forms and functions.
What does it mean for the future?
These findings confirm that DNA methylation is essential for creating different brain cell types. They also show how early disruptions to this process could contribute to neurodevelopmental conditions.
“By uncovering these mechanisms, our work provides new insights into how conditions such as autism and schizophrenia may arise – and brings us one step closer to more effective ways to predict, understand and support mental health across the life span.”
Read the fully study 👉 Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex: Cell Genomics
