Association of Adverse Childhood Experiences With Accelerated Epigenetic Aging in Midlife

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Abstract
Adverse childhood experiences (ACEs) have been associated with a range of social disadvantages in adulthood.1,2 Individuals with a high burden of ACEs are more likely to engage in risky health behaviors,3 which can be associated with various age-related health outcomes.3-9 In a life-course perspective, ACEs like trauma in childhood were also associated with accelerated phenotypic and functional aging processes in later life.10 Detrimental outcomes associated with ACEs accumulate in a dose-response fashion, and experiencing 4 or more ACEs has been associated with various negative health outcomes.8,11-14 Studies on the molecular mechanisms of ACEs have found methylation changes in genes, including NR3C1 and FKBP5, that are associated with glucocorticoid-mediated stress response,15-18 as well as genes, such as SCL6A3, SKA2, and BDNF, associated with other stress mediators.19-21 However, associations were limited to certain demographic subgroups in most studies, and underlying mechanisms remain elusive.22

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