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While our circadian body clock determines our preferred rhythm of sleep or wakefulness, a relatively new concept – the epigenetic clock – could inform us about how quickly we age and how prone we are to diseases of the elderly.
People age at different rates, with some people developing both traits and diseases related to aging earlier in life than others. If we know more about this so-called “biological age”, we can learn more about how we can prevent age-related diseases such as dementia. Epigenetic markers control the extent to which genes are turned on and off in the various types of cells and tissues that make up a human body. Unlike our genetic code, these epigenetic markers change over time, and these changes can be used to accurately predict the biological age of a DNA sample.
Now scientists at the University of Exeter have developed a new epigenetic clock specifically for the human brain. Because it uses tissue samples from the human brain, the new clock is far more accurate than previous versions that were based on blood samples or other tissues. The researchers hope that their new watch, published in Brain and funded by the Alzheimer’s Society, will provide insight into the potential effects of accelerated aging in the brain on brain diseases such as Alzheimer’s and other forms of dementia.
Professor Jonathan Mill from the University of Exeter, who led the research team, said, “The research area of epigenetic clocks is really exciting and it can help us understand the mechanisms of aging. Our new clock will help us research accelerated aging in humans Brain. Because we are using brain samples, this is clearly not a model for living people to tell how quickly they will age, but we can apply it to donated brain tissue to help us learn more about the factors that contribute to brain diseases like dementia involved. “
The research team took a unique approach to analyzing 1,397 human brain samples from people aged between 1 and 108 years. Previous models were largely based on blood samples from middle-aged people. Hence, the wide age range is another strength that makes the new model a more accurate predictor. The team analyzed an epigenetic marker known as DNA methylation in the human cortex, a region of the brain that is involved in cognition and is 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 (BDR) cohort funded by the Alzheimer Society and Alzheimer Research UK, as well as in a dataset of 1,175 blood samples.
Gemma Shireby, who was the lead author of the research as part of her doctorate. at the University of Exeter said, “Our new epigenetic body clock has dramatically outperformed previous models in predicting biological age in the human brain. Our study shows the importance of using tissue relevant to the mechanism you are at want to study the development of epigenetic clock models in this case, the use of brain tissue ensures that the epigenetic clock is properly calibrated to study dementia. “
The research team is currently working on using the model on brain samples from people with Alzheimer’s disease. They assume that they will find evidence of increased biological aging in these samples.
Fiona Carragher, director of research and influencing for the Alzheimer’s Society, said, “Epigenetics is a thriving area of dementia research, and this study is extremely valuable as we continue to examine the role and impact of Alzheimer’s disease on brain aging Understanding Better When We Can Be More Accurate When we can predict the aging of the brain and uncover the underlying causes of this highly complex disease, we have the greatest chance of developing effective treatments that could slow brain progression.
“This work is only possible thanks to the support of charities like the Alzheimer’s Society who funded this work, but we need more investment. The government must commit to doubling funding for dementia research so that we can do that Maintain momentum and give hope to the 850,000 people who can live with dementia in the UK today. “
The paper published in Brain entitled “Recalibrating the Epigenetic Clock: Impact on Assessing Biological Age in the Human Cortex”.
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Recalibrating the epigenetic clock: implications for assessing biological age in the human cortex, Brain (2020). akademisch.oup.com/brain/article… 0.1093 / brain / awaa334
Brain provided by the University of Exeter
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