“GrimAge,” an epigenetic predictor of mortality, is accelerated in Major Depressive Disorder
“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 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 two 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.
Wu Gwyneth W. Y.、Prather Aric、Hammamieh Rasha、Epel Elissa、Protsenko Ekaterina、Gautam Aarti、Mellon Synthia H.、Wolkowitz Owen M.、Jett Marti、Reus Victor、Rampersaud Ryan、Yang Ruoting、Nier Brent、Hough Christina M.
Weill 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, Walter Reed Army Institute of ResearchWeill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of MedicineUniversity of California San Francisco (UCSF) School of MedicineMedical Readiness Systems Biology, 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 MedicineUS Army MRDC and 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, 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 Medicine||Department of Psychology, University of California Los Angeles (UCLA)
神经病学、精神病学基础医学生物科学研究方法、生物科学研究技术
Wu Gwyneth W. Y.,Prather Aric,Hammamieh Rasha,Epel Elissa,Protsenko Ekaterina,Gautam Aarti,Mellon Synthia H.,Wolkowitz Owen M.,Jett Marti,Reus Victor,Rampersaud Ryan,Yang Ruoting,Nier Brent,Hough Christina M..“GrimAge,” an epigenetic predictor of mortality, is accelerated in Major Depressive Disorder[EB/OL].(2025-03-28)[2025-06-06].https://www.medrxiv.org/content/10.1101/2020.12.25.20248290.点此复制
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