Researchers at the University of Exeter have created a new epigenetic clock for the human brain. Because it uses human brain tissue samples, it is a far more accurate clock than previous versions based on blood samples or other tissues.
The research area of epigenetic clocks is a really exciting, and has the potential to help us understand the mechanisms involved in aging. Our new clock will help us explore accelerated aging in the human brain. As we’re using brain samples, this clearly isn’t a model that can be used in living people to tell how fast they’ll age—however, we can apply it to donated brain tissue to help us learn more about the factors involved in brain diseases such as dementia,
said team leader Professor Jonathan Mill, of the University of Exeter. The researchers hope that their new clock1 will provide insight into how accelerated aging in the brain might be associated with brain diseases such as Alzheimer’s disease and other forms of dementia.
People age at various rates. Some individuals develop both characteristics and diseases related to aging earlier in life than others. Understanding more about this so-called biological age could help us learn more about how we can prevent diseases associated with age, such as dementia.
Epigenetic markers, such as DNA methylation, control the extent to which genes are switched on and off across the different cell-types and tissues that make up a human body. Unlike our genetic code, these epigenetic marks change over time, and these changes can be used to accurately predict biological age from a DNA sample.
The research team took the novel approach of analyzing 1,397 human brain samples, from people aged between one and 108. Previous models have largely been based on blood samples from people in mid life, so the wide age range is another strength that makes the new model a more accurate predictor. The team analyzed DNA methylation in the human cortex, a brain region involved in cognition and implicated in diseases such as Alzheimer’s disease.
The team identified 347 DNA methylation sites that optimally predict age in the human cortex, when analyzed in combination. They then tested their model in a separate collection of 1,221 human brain samples from the Brains for Dementia Research cohort, which is funded by the Alzheimer’s Society and Alzheimer’s Research UK, and in a dataset of 1,175 blood samples.
Our new epigenetic body clock dramatically outperformed previous models in predicting biological age in the human brain. Our study highlights the importance of using tissue that is relevant to the mechanism you want to explore when developing epigenetic clock models. In this case, using brain tissue ensures the epigenetic clock is properly calibrated to investigate dementia,
said first author Gemma Shireby.
The research team is now working on using the model on brain samples of people who had Alzheimer’s disease. They hypothesize that they will find evidence for elevated biological aging in these samples.
Gemma L Shireby, Jonathan P Davies, Paul T Francis, Joe Burrage, Emma M Walker, Grant W A Neilson, Aisha Dahir, Alan J Thomas, Seth Love, Rebecca G Smith, Katie Lunnon, Meena Kumari, Leonard C Schalkwyk, Kevin Morgan, Keeley Brookes, Eilis Hannon, Jonathan Mill Recalibrating the epigenetic clock: implications for assessing biological age in the human cortex Brain, awaa334, 28 October 2020 ↩︎