New research shows epigenetic age can predict cognitive function

Epigenetic markers of cognitive aging can predict performance on cognitive tests later in life, according to new research.

Epigenetic markers of cognitive aging can predict performance on cognitive function tests later in life, according to new research published in the journal Aging.

This epigenetic age score could be used to identify individuals at risk of later dementia, facilitating early intervention that would otherwise not be possible, according to Lifang Hou, MD, PhD, chief of Cancer Epidemiology and Prevention in the Department of Preventive Medicine and senior author of the study.

Longevity.Technology: Recently, we covered the creation of one of the largest epigenetic datasets in history, discussing how the data could be leveraged for pioneer landmark research for longevity science, as well as being of benefit to the insurance industry with life insurance becoming hyper-personalised and responsive to year-on-year choices – all determined by epigenetic testing.

Chronological age is just a number, but an epigenetic age score is a better reflection of how old parts of your body actually are – and could be a significant motivator for change. “This could help individuals understand they need to modify their lifestyle and bring awareness to people with accelerated aging,” said Hou [1].

By the time a diagnosis of Alzheimer’s disease or dementia is made, significant neurodegeneration has usually already occurred. However, before that point is reached, cognitive function questionnaires or brain imaging can reveal sub-clinical cognitive decline – but imaging is expensive and cognitive function questionnaires can produce inconsistent results.

“There is a need for easily accessed, quantitative biomarkers,” said Yinan Zheng, PhD, assistant professor of Preventive Medicine in the Division of Cancer Epidemiology and Prevention [1].

Specific epigenetic changes have already been linked with aging and aging-related diseases, so scientists at Northwestern University Feinberg School of Medicine developed an epigenetic age score to quantify the biological age. The score measures DNA methylation of specific genomic regions, which alters expression levels of several genes, including epigenetic “clock” genes and other genes related to immune function, adipocytokine signalling, lipid metabolism and inflammation.

This score – which the researchers are terming “epigenetic age” – is designed to be a more useful interpretation of aging. Someone with a chronological age of 50 but an epigenetic age of 60 would be considered to have accelerated epigenetic aging.

READ MORE: Epigenetics – or why you are more than just your genes

The researchers then applied this epigenetic age at two different time points to middle-aged participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a long-term study of cardiovascular risk factors which began in 1983 with participants in young adulthood.

Using brain imaging data to quantify “brain age” in the same participants, the research team assessed these two aging markers, both assessed at two time points, and investigated those same participants’ performance on cognitive function tests.

Accelerated epigenetic age in midlife was predictive of cognitive performance five to ten years later. Importantly, epigenetic age and brain age were weakly correlated, underlining their complementary information relevant to accelerated cognitive aging. In fact, adding brain age information into the mix further improved the prediction accuracy of epigenetic age, according to the authors [2].

“Epigenetic age is a relatively stable biomarker with strong long-term predictive performance for cognitive function, whereas a brain age biomarker may change more dynamically in temporal association with cognitive decline,” Zheng said [1].

This epigenetic age, coupled with brain age, could be a useful early diagnostic tool to identify patients at risk of dementia or Alzheimer’s disease; however, the authors cautioned that these aging markers need further calibration and validation in an older cohort with clinical dementia events [2].

Further research is warranted, and Hou and Zheng said they are actively searching for collaborators who have access to patient cohorts that fit these requirements.

READ MORE: NEOGEN and FOXO Technologies create one of the largest epigenetic datasets in history

[1] https://news.feinberg.northwestern.edu/2022/04/epigenetic-age
[2] https://www.aging-us.com/article/203918

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