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Epigenetic clock is accelerated in major depressive disorder

Researchers have found that an epigenetic clock and predictor of mortality – GrimAge – is accelerated in individuals with major depressive disorder.

Major depressive disorder

Major depressive disorder (MDD) is the leading cause of disability worldwide. It is also associated with early mortality and is an independent risk factor for several diseases associated with ageing. These include cardiovascular disease, dementia, osteoporosis and also diabetes. The pathophysiology underlying increased rates of somatic disease in MDD remains unknown. Researchers have proposed that MDD represents a state of accelerated ageing.

In recent years, epigenetic age has emerged as a promising measure of cellular ageing. Compared to biological age, epigenetic age shows strong associations with mortality. It is based on the fact that chronological age has predictable effects on DNA methylation patterns. Epigenetics clock consist of small sets of CpG sites whose methylation patterns yield an estimate of biological or cellular age – ‘DNAm Age’. Different clocks have a different set of CpG sites. When an individual’s DNAm Age exceeds their chronological age, they are said to experience ‘Epigenetic Age Acceleration’.

An accelerated epigenetic clock

Epigenetic clocks have shown promise in their ability to capture accelerated ageing in psychiatric diseases. GrimAge is a unique epigenetic clock in that it was trained on time-to-death data. This predictor has outperformed previous models in its ability to predict both morbidity and mortality. However, it has yet to be investigated in MDD.

In this paper, published in Translational Psychiatry, researchers measured GrimAge in 49 somatically healthy untreated individuals with MDD and 60 age-matched healthy controls. The team found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age compared to healthy controls. This difference remained significant after controlling for several factors, including sex, current smoking status and also BMI.

These findings suggest that there is an underlying biological mechanism accelerating cellular ageing in some individuals with MDD.

Katerina Protsenko, lead author, stated:

“This is shifting the way we understand depression, from a purely mental or psychiatric disease, limited to processes in the brain, to a whole-body disease.

This should fundamentally alter the way we approach depression and how we think about it – as a part of overall health.”

The researchers hope to determine whether anti-depressants may mitigate the methylation patterns in hopes of normalising the cellular ageing process.

Image credit: By Thomas Northcut –

More on these topics

Depression / Epigenetic Clocks / Epigenetics