“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder
Abstract Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer’s disease. However, the pathophysiology underlying increase...
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2021-04-01
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Series: | Translational Psychiatry |
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doaj-1ed1f36ac858446c87cd14a337d982232021-04-11T11:43:01ZengNature Publishing GroupTranslational Psychiatry2158-31882021-04-011111910.1038/s41398-021-01302-0“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorderEkaterina Protsenko0Ruoting Yang1Brent Nier2Victor Reus3Rasha Hammamieh4Ryan Rampersaud5Gwyneth W. Y. Wu6Christina M. Hough7Elissa Epel8Aric A. Prather9Marti Jett10Aarti Gautam11Synthia H. Mellon12Owen M. Wolkowitz13University of California San Francisco (UCSF) School of MedicineMedical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of ResearchWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineMedical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of ResearchWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineUS Army MRDC and Walter Reed Army Institute of ResearchMedical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of ResearchDepartment of OB-GYN and Reproductive Sciences, University of California San Francisco (UCSF) School of MedicineWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineAbstract Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer’s disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Among such metrics, estimators of biological age based on predictable age-related patterns of DNA methylation (DNAm), so-called ‘epigenetic clocks’, have shown particular promise for their ability to capture accelerated aging in psychiatric disease. The recently developed DNAm metric known as ‘GrimAge’ is unique in that it was trained on time-to-death data and has outperformed its predecessors in predicting both morbidity and mortality. Yet, GrimAge has not been investigated in MDD. Here we measured GrimAge in 49 somatically healthy unmedicated individuals with MDD and 60 age-matched healthy controls. We found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age (‘AgeAccelGrim’) compared to healthy controls (p = 0.001), with a median of 2 years of excess cellular aging. This difference remained significant after controlling for sex, current smoking status, and body-mass index (p = 0.015). These findings are consistent with prior suggestions of accelerated cellular aging in MDD, but are the first to demonstrate this with an epigenetic metric predictive of premature mortality.https://doi.org/10.1038/s41398-021-01302-0 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ekaterina Protsenko Ruoting Yang Brent Nier Victor Reus Rasha Hammamieh Ryan Rampersaud Gwyneth W. Y. Wu Christina M. Hough Elissa Epel Aric A. Prather Marti Jett Aarti Gautam Synthia H. Mellon Owen M. Wolkowitz |
spellingShingle |
Ekaterina Protsenko Ruoting Yang Brent Nier Victor Reus Rasha Hammamieh Ryan Rampersaud Gwyneth W. Y. Wu Christina M. Hough Elissa Epel Aric A. Prather Marti Jett Aarti Gautam Synthia H. Mellon Owen M. Wolkowitz “GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder Translational Psychiatry |
author_facet |
Ekaterina Protsenko Ruoting Yang Brent Nier Victor Reus Rasha Hammamieh Ryan Rampersaud Gwyneth W. Y. Wu Christina M. Hough Elissa Epel Aric A. Prather Marti Jett Aarti Gautam Synthia H. Mellon Owen M. Wolkowitz |
author_sort |
Ekaterina Protsenko |
title |
“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder |
title_short |
“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder |
title_full |
“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder |
title_fullStr |
“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder |
title_full_unstemmed |
“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder |
title_sort |
“grimage,” an epigenetic predictor of mortality, is accelerated in major depressive disorder |
publisher |
Nature Publishing Group |
series |
Translational Psychiatry |
issn |
2158-3188 |
publishDate |
2021-04-01 |
description |
Abstract Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer’s disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Among such metrics, estimators of biological age based on predictable age-related patterns of DNA methylation (DNAm), so-called ‘epigenetic clocks’, have shown particular promise for their ability to capture accelerated aging in psychiatric disease. The recently developed DNAm metric known as ‘GrimAge’ is unique in that it was trained on time-to-death data and has outperformed its predecessors in predicting both morbidity and mortality. Yet, GrimAge has not been investigated in MDD. Here we measured GrimAge in 49 somatically healthy unmedicated individuals with MDD and 60 age-matched healthy controls. We found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age (‘AgeAccelGrim’) compared to healthy controls (p = 0.001), with a median of 2 years of excess cellular aging. This difference remained significant after controlling for sex, current smoking status, and body-mass index (p = 0.015). These findings are consistent with prior suggestions of accelerated cellular aging in MDD, but are the first to demonstrate this with an epigenetic metric predictive of premature mortality. |
url |
https://doi.org/10.1038/s41398-021-01302-0 |
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