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Cellular Aging Accelerated in Patients With Major Depressive Disorder

April 16, 2021

Somatically healthy people with major depressive disorder showed a median 2 years’ excess cellular aging, compared with age-matched healthy control subjects, in a study published online in Translational Psychiatry.

“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,” said study co-senior author Owen Wolkowitz, MD, professor of psychiatry at the University of California, San Francisco (UCSF). “That's always been a mystery, and that’s what led us to look for signs of aging at the cellular level.”

For the study, researchers used the GrimAge epigenetic clock, a metric of age-related DNA methylation trained on time-to-death data to predict morbidity and mortality. Investigators collected blood samples from 49 unmedicated patients with major depressive disorder and 60 healthy control subjects matched for chronological age and analyzed their methylation rates using GrimAge.

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Participants with major depressive disorder exhibited a significantly higher GrimAge relative to their chronological age compared with healthy controls. The study identified a median of 2 years of excess cellular aging in patients, and the difference remained significant after controlling for sex, current smoking status, and body mass index.

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

At this point, investigators are unsure whether depression causes the altered methylation in certain people, or whether depression and methylation are associated with another underlying factor. Altered methylation patterns have also been identified in people with posttraumatic stress disorder, they noted.

“As we continue our studies, we hope to find out whether addressing the major depressive disorder with antidepressants or other treatments alters the methylation patterns,” said study co-senior author and UCSF professor Synthia Mellon, PhD, “which would give us some indication that these patterns are dynamic and can be changed.”

—Jolynn Tumolo


Protsenko E, Yang R, Nier B, et al. "GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder. Translational Psychiatry. 2021;11(1):193.

Accelerated cellular aging associated with mortality seen in depressed individuals [press release]. San Francisco, California: University of California San Francisco; April 6, 2021.

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