Depression Makes Your Genes Age Faster, New Study Finds

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Depression Makes Your Genes Age Faster, New Study Finds

Depression impacts health and accelerates aging. Beyond its disruptive effects on everyday activities and quality of life, depression has long-lasting health consequences that can increase the risk for other conditions and promote aging. Research shows that depression is an independent risk factor for several diseases, such as cardiovascular disease, dementia, osteoporosis, and diabetes, and is associated with early mortality (1,2).

A study published April 6, 2021, in Translational Psychiatry showed that cells from individuals with Major Depressive Disorder (MDD) had accelerated aging of approximately two years, suggesting increased mortality risk, compared to healthy individuals of the same chronological age. These findings from Protsenko and colleagues at the University of California San Francisco (UCSF) provide new insight into the increased mortality and morbidity associated with the condition, suggesting that there is an underlying biological mechanism accelerating cellular aging in some MDD sufferers.

“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,” said Katerina Protsenko, a medical student at UCSD and lead author of the study. “This should fundamentally alter the way we approach depression and how we think about it — as a part of overall health.”

Genetic “clocks” show the true age of your genes

For some time, scientists speculated that there must be some kind of underlying mechanism of accelerated biological or cellular aging that is triggered by depression. In recent years, scientists have developed ways to measure the genetic age of an individual, by examining methylation patterns in DNA. As we age, certain parts of our genome get bound to a compound known as a methyl group. This process of methylation occurs at a constant and steady rate in healthy individuals, but the process can be disrupted by disease or hardship and can lead to changes in the ways that genes are activated.

The examination of methylation patterns has allowed scientists to compare an individual’s chronological age against their cellular age by examining the methylation rate of their DNA. A higher methylation rate indicates accelerated aging. Researchers have taken this genetic age assessment one step further by including other biomarkers that predict mortality to better understand the impact of risk factors, such as smoking with chronic disease and health outcomes.

One such assessment is the GrimAge clock (3). By examining the rates of methylation and other known biomarkers for disease, GrimAge can predict the time of onset of several conditions like cardiovascular diseases and type 2 diabetes.

Depression makes genetic clocks tick faster

Depression makes genetic clocks tick faster

A recent study published in the journal Translational Psychiatry uses the GrimAge clock to show the effects of depression on cellular aging and mortality prediction. Dr. Owen Wolkowitz, the co-author of the study, said, “One of the things that's remarkable about depression is that sufferers have unexpectedly higher rates of age-related physical illnesses and early mortality, even after accounting for things like suicide and lifestyle habits. That's always been a mystery, and that's what led us to look for signs of aging at the cellular level."

The study compared data from 49 individuals diagnosed with MDD against a group of 60 healthy participants. To keep the results as accurate as possible, the authors made sure that the two groups of participants were as similar as possible. Age, sex, BMI, race, and ethnicity were similar in both groups. However, there was a significant difference in one risk factor — participants in the depressed group reported more frequent use of tobacco products.

Using GrimAge to score genetic age, Protsenko and colleagues showed that the depression group had a significantly higher age acceleration rate. Compared to the healthy group, depressed participants’ GrimAge scores equated to two years of accelerated aging. Even after the researchers adjusted for the higher smoking rate in this group, these results didn’t change. These findings are significant because they show that even though aging is a known cause of accelerated aging and a risk factor for several diseases, depression was the main driver for the accelerated rate of aging seen in the depressed group.

Will treating depression restore proper aging?

Will treating depression restore proper aging?

The study’s findings are in line with results obtained from other research that show genetic changes caused by depression that can lead to premature aging. One study from the Netherlands had previously found that depression aged participants the equivalent of 8 months (4). The results from this study show a higher increase in aging, possibly because of the additional lifestyle factors that the study examined, such as smoking.

Although these results show a clear effect on DNA methylation and genetic age as measured by the GrimAge method, the authors believe that there is no real way to correlate conditions like depression with actual mortality rates yet. Future studies that follow participants over a long period of time will provide the data necessary to examine the effects on mortality. Researchers hope to continue examining the relationship between depression and aging to see if available treatments have a restorative effect on genetic age.

“As we continue our studies, we hope to find out whether addressing the MDD with anti-depressants or other treatments alters the methylation patterns, which would give us some indication that these patterns are dynamic and can be changed,” said Synthia Mellon, Ph.D., professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences at UCSF and co-senior author of the study. More studies will be needed to understand if these changes can be reverted.

Show references

  1. Wolkowitz OM, Reus VI, Mellon SH. Of sound mind and body: depression, disease, and accelerated aging. Dialogues Clin Neurosci. 2011;13(1):25-39. doi:10.31887/DCNS.2011.13.1/owolkowitz
  2. Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis.  [published correction appears in JAMA Psychiatry. 2015 Dec;72(12):1259] . JAMA Psychiatry. 2015;72(4):334-341. doi:10.1001/jamapsychiatry.2014.2502
  3. Protsenko E, Yang R, Nier B, et al. "GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder. Transl Psychiatry. 2021;11(1):193. Published 2021 Apr 6. doi:10.1038/s41398-021-01302-0
  4. Han LKM, Aghajani M, Clark SL, et al. Epigenetic Aging in Major Depressive Disorder. Am J Psychiatry. 2018;175(8):774-782. doi:10.1176/appi.ajp.2018.17060595

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