Scientists have developed a clock that could provide insights into how accelerated ageing in the brain might be associated with Alzheimer’s disease and other forms of dementia.
While the circadian body clock dictates our preferred rhythm of sleep or wakefulness, the epigenetic clock could shed light on how swiftly people age, and how prone they are to diseases of old age, researchers say.
University of Exeter scientists used human brain tissue samples to develop the clock, making it more accurate than previous versions that were based on blood samples or other tissues.
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“The research area of epigenetic clocks is really exciting, and has the potential to help us understand the mechanisms involved in ageing,” said Professor Jonathan Mill, who led the research team.
“Our new clock will help us explore accelerated ageing 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.”
The team analysed an epigenetic marker – which tells genes to switch on or off – known as DNA methylation in the human cortex, a brain region involved in cognition and implicated in diseases such as Alzheimer’s disease.
They identified 347 DNA methylation sites that optimally predict age in the human cortex, when analysed in combination.
Researchers then tested their model in a separate collection of 1,221 human brain samples from the Brains for Dementia Research (BDR) cohort, which is funded by the Alzheimer’s Society and Alzheimer’s Research UK, and in a dataset of 1,175 blood samples.
Methylation data has been used to develop biomarkers of ageing, referred to as epigenetic clocks. These clocks have been widely used to identify differences between chronological age and biological age in health and disease, including neurodegeneration, dementia and other brain phenotypes, the researchers say.
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“Our new epigenetic body clock dramatically outperformed previous models in predicting biological age in the human brain,” said Gemma Shireby, who was first author of the research as part of her PhD at the University of Exeter.
“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.”
The research is published in the journal Brain, and funded by Alzheimer’s Society.
What is epigenetics?
Francis Crick and James Watson became household names for their 1953 discovery of the structure of DNA, and that breakthrough formed the basis for our understanding of how attributes are passed on from one generation to the next.
But DNA – the genome – isn’t the whole of the story. Since the 1970s, the role of the ‘epigenome’ has come under ever-greater scrutiny. The epigenome is the name given to tiny chemical modifications made by factors such as environment and diet to DNA and the proteins it wraps around.
Epigenetic research studying these modifications has thrown up some surprising results.