Accelerated cellular aging associated with deaths observed in depressed individuals

Researchers said that the DNA markers in the cells of MDD patients appear two years greater than those in healthy controls

Cells taken from individuals with major depressive disorder (MDD) have been found to have higher-than-expected rates of methylation at specific sites on their DNA, compared to cells from healthy individuals without major depressive disorder, according to a study by a multidisciplinary team of UCSD scientists In San Francisco. Collaborate with others. Methylation is a process by which DNA is chemically modified at specific sites, leading to changes in the expression of specific genes. The methylation of certain groups of genes, called “DNA methylation clocks,” usually changes in predictable ways as people age, but the rate of these changes varies between people. The methylation patterns in individuals with MDD indicate that their cellular age is, on average, accelerated compared to the matched healthy controls.

In the study published April 6, 2021 in Translational Psychiatry, Blood samples taken from individuals with MDD were analyzed for methylation patterns using the “GrimAge” watch – a mathematical algorithm designed to predict an individual’s remaining life based on patterns of cellular methylation. Individuals with MDD showed a significantly higher GrimAge score, indicating an increased risk of mortality, compared to healthy individuals of the same chronological age – an average of roughly two years on the GrimAge clock.

Individuals with MDD showed no outward signs of age-related pathology, as they were examined and physical health controls prior to entering the study. The methylation patterns associated with the risk of death persisted even after accounting for lifestyle factors such as smoking and BMI. These results provide new insight into the condition-related mortality and increased morbidity, suggesting an underlying biological mechanism that accelerates cell aging in some people with major depressive disorder.

“This changes the way we understand depression, from a mental or psychological illness that is limited to processes in the brain, to a disease that affects the whole body,” said Katrina Protenko, a medical student at the University of California, San Francisco, and lead author of the study. “This should fundamentally change the way we approach depression and how we think about it – as part of overall health.”

Chronic liver disorder is one of the most common health problems globally, according to the World Health Organization, about 300 million people (4.4% of the population) suffer from some form of depression. MDD is associated with higher incidence and mortality associated with increased rates of cardiovascular disease, diabetes, and Alzheimer’s disease among those affected.

“One of the things that is striking about depression is that sufferers have unexpectedly higher rates of age-related physical illness and premature deaths, even after accounting for things like suicide and lifestyle habits,” said Owen Wolkowitz, a professor of psychiatry and a member. From the Weil Neuroscience Institute at the University of California, San Francisco, is a senior co-author of the study. “This has always been a mystery, and this is what motivated us to look for signs of aging at the cellular level.”

Researchers collected blood samples from 49 individuals with MDD who did not receive treatment prior to the study and 60 healthy individuals of the same chronological age. They analyzed the methylation rates of both groups with a GrimAge watch. While there are many methylation-based longevity algorithms, GrimAge is the only one that specifically relies on methylation patterns associated with mortality.

Researchers say they don’t yet know whether depression causes methylation in certain individuals, or whether depression and methylation are related to another underlying factor. It is possible that some individuals have a genetic predisposition to produce specific methylation patterns in response to stress, but this has not been well studied. Changes in methylation patterns have previously been observed in individuals with PTSD.

Going forward, researchers hope to determine whether drug therapies or therapy may mitigate some of the methylation changes associated with MDD in hopes of normalizing the cellular aging process in affected individuals before they develop. Although GrimAge methylation clock has been associated with deaths in other populations, no studies to date have determined whether this methylation pattern also predicts mortality in MDD.

“As we continue our studies, we hope to see if treating major depressive disorder with antidepressants or other therapies alters methylation patterns, which should give us some indication that these patterns are dynamic and can be changed,” said Cynthia Mellon, PhD. , Professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of California, San Francisco and co-author of the study.


Authors: Katrina Protenko was the lead author of the study. Owen M. Wolkowitz, MD, Cynthia H Mellon, PhD, and Victor I. Rios, MD were the two senior co-authors of the study. The study was conducted in collaboration with Ruoting Yang, Rasha Hammamieh, Marti Jett, Aarti Gautam, and other scientists from Walter Reed Army Research Institute, Silver Spring, MD.

Funding: This study was funded by grants from the National Institute of Mental Health (NIMH) (grant number R01-MH083784), the O’Shaughnessy Foundation, the Tinberg family, grants from the UCSF Academic Senate, the UCSF Research Assessment and Appropriation Committee (REAC). This project was also supported by the National Institutes of Health / National Research Resource Center (NIH / NCRR) and the National Center for Transformational Science Development, National Institutes of Health, through UCSF-CTSI Grant Numbers UL1 RR024131 and TL-1 TR001871

Disclosures: The authors have no financial relationships related to this article to disclose.

About UCSF: The University of California, San Francisco (UCSF) has an exclusive focus on health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which operates as the primary academic medical center at UCSF, includes highly-rated specialist hospitals and other clinical programs, and has branches throughout the Gulf region. The University of California, San Francisco, School of Medicine has a regional campus in Fresno. Learn more at, or check out our fact sheet.

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Jason Alvarez
[email protected]http: // dx.Resonate.Deer /10.1038 /s41398-021-01302-0

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