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      Accelerated epigenetic aging mediates link between adverse childhood experiences and depressive symptoms in older adults: Results from the Health and Retirement Study

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          Abstract

          Adverse childhood experiences (ACEs) increase risk for depression at subsequent ages and have been linked to accelerated biological aging. We hypothesize that accelerated epigenetic aging may partially mediate the link between ACEs and depression. This study examines 3 three second-generation epigenetic aging measures (viz., GrimAge, PhenoAge, and DunedinPoAm38) as mediators of the link between ACEs and depressive symptoms in older adulthood. We utilize structural equation modeling to assess mediation in the Health and Retirement Study (N = 2672). Experiencing ACEs is significantly associated with an older GrimAge and a faster pace of aging via the DunedinPoAm38. Having an older GrimAge and faster DunedinPoAm38 pace of aging were also significantly associated with more depressive symptoms. PhenoAge was not significantly associated with depressive symptoms and was only associated with experiencing three ACEs. These associations were reduced by socioeconomic and lifestyle factors, including obesity and substance use. GrimAge explained between 9 and 14% of the association between ACEs and adult depressive symptoms, and DunedinPoAm38 explained between 2 and 7% of the association between ACEs and adult depressive symptoms. Findings indicate accelerated aging, as measured by GrimAge and DunedinPoAm38, is associated with ACEs and with depressive symptoms in older Americans. Findings also show these epigenetic aging measures mediate a portion of the association between ACEs and adult depressive symptoms. Epigenetic aging may represent a physiological mechanism underlying the link between early life adversity and adult depression. Weight maintenance and substance use are potentially important areas for intervention.

          Highlights

          • Accelerated aging (GrimAge and DunedinPoAm38) is associated with ACEs and with depressive symptoms in older Americans.

          • These associations were reduced by socioeconomic and lifestyle factors, including obesity and substance use.

          • GrimAge explained between 9 and 14% of the association between ACEs and adult depressive symptoms.

          • DunedinPoAm38 explained between 2 and 7% of the association between ACEs and adult depressive symptoms.

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          Most cited references55

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          The CES-D Scale: A Self-Report Depression Scale for Research in the General Population

          L Radloff (1977)
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            The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis

            A growing body of research identifies the harmful effects that adverse childhood experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or exposure to domestic violence) have on health throughout life. Studies have quantified such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of findings from studies measuring the effect of multiple ACE types has been done.
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              An epigenetic biomarker of aging for lifespan and healthspan

              Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
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                Author and article information

                Contributors
                Journal
                SSM Popul Health
                SSM Popul Health
                SSM - Population Health
                Elsevier
                2352-8273
                16 March 2022
                March 2022
                16 March 2022
                : 17
                : 101071
                Affiliations
                [a ]University of Southern California, United States
                [b ]University of California, Los Angeles, United States
                Author notes
                []Corresponding author. 3715 McClintock Ave, Los Angeles, CA, 90089, United States. klopack@ 123456usc.edu
                Article
                S2352-8273(22)00050-7 101071
                10.1016/j.ssmph.2022.101071
                8933834
                35313610
                46cd1471-75e1-4f96-a72b-9e9bdbffc385
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 17 December 2021
                : 11 March 2022
                : 12 March 2022
                Categories
                Article

                ageing,depression,adverse childhood events,epigenetic aging,aces, adverse childhood events

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