Traumatic Stress and Accelerated Cellular Aging: From Epigenetics to Cardiometabolic Disease

Wolf, Erika J.; Morrison, Filomene G.

doi:10.1007/s11920-017-0823-5

Cited by 59 publications

(50 citation statements)

References 105 publications

(124 reference statements)

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“…We observed increases in Hannum and Horvath age acceleration associated with anxiety, PTSD and low income that were generally of greater size than for mAA (although with wider confidence intervals due to the smaller sample size). Meta‐analyses have shown that both PTSD (Wolf & Morrison, 2017) and low socio‐economic position (Fiorito et al, 2017) are associated with higher Hannum age acceleration. We did not observe any evidence for an association between depression and Hannum or Horvath age acceleration, suggesting epigenetic and metabolomic aging measures may be sensitive to separate dimensions of mental health.…”

Section: Discussionmentioning

confidence: 99%

“…Aging has been defined as the “time‐dependent decline of functional capacity and stress resistance, associated with increased risk of morbidity and mortality” (Burkle et al, 2015). Environmental stressors, including lifestyle and social adversity (Stringhini et al, 2018), psychological disorders (Chiu et al, 2018; Wolf & Morrison, 2017), and genetic factors (McDaid et al, 2017) may influence the aging process, leading to differing aging rates. Traditionally, quantitative assessment of “the rate of aging” relies on the analysis of mortality curves of populations.…”

Section: Introductionmentioning

confidence: 99%

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Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

et al. 2020

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Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

et al. 2020

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“…Notably, systemic inflammation may underlie the pathophysiology of PTSD, as well as the consistent link between PTSD and chronic medical conditions associated with aging, such as cardiovascular, metabolic, autoimmune, and neurodegenerative diseases [4][5][6][7][8], and other markers of accelerated aging [6,7,[9][10][11][12][13][14]. This dysregulated inflammatory state is itself partially coordinated by maladaptive alterations of hypothalamic-pituitary adrenal (HPA) axis activity and sympathetic nervous system (SNS) sensitivity/responsivity [15,16], which affect both peripheral immune cells in blood and neuroimmune dynamics in brain.…”

Section: Introductionmentioning

confidence: 99%

Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood

Kim

Uddin

2020

Biol Sex Differ

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Background: While post-traumatic stress disorder (PTSD) is defined by behavioral/cognitive symptoms most directly relevant to brain function, it can be considered a systemic disorder characterized by a distinct inability to reinstate homeostasis after trauma. Methods: In this study, we conducted a secondary analysis of gene expression profiles in key PTSD-relevant tissues, namely blood, amygdala, and hippocampus, from a rat model of PTSD, to identify sex-specific and shared processes associated with individual differences in response to recent trauma exposure. Results: Our findings suggest both shared and sex-specific mechanisms underlying individual differences associated with vulnerability and resilience to trauma in hippocampus, amygdala, and blood. By disentangling cell composition from transcriptional changes, we found higher proportions of hippocampal oligodendrocytes in the PTSD-like, extreme behavioral response (EBR) group for both sexes and also identified modules for transcriptional activity associated with group differences (i.e., response to trauma) in the hippocampus that appeared to be sex-specific. By contrast, we found prominent sex differences, but no group differences, in amygdalar cell composition, and both shared and sex-specific modules representing PTSD-relevant transcriptional activity in the amygdala. Across amygdala and hippocampus, both sex-specific and shared processes were relevant to an overarching framework for EBR implicating disrupted TNFα/NFκΒ signaling and excitatory/inhibitory imbalance in dysregulated synaptic/structural plasticity with important implications for fear learning and memory. Our main finding in peripheral blood was consistent with the human literature and identified wound healing processes and hemostasis to be upregulated in the resilient, minimal behavioral response (MBR) group across sexes, but disrupted in a sexually dimorphic manner in the EBR group. Conclusion: In contrast to the varied characterization of the PTSD-like EBR group, characterization of MBR across blood, amygdala, and hippocampus suggests a common theme of upregulated wound healing and extracellular matrix (ECM) remodeling shared between sexes. In all, we identified differential oligodendrocyte proportions in hippocampus between PTSD-like EBR and resilient MBR, and identified processes and pathways that characterize the EBR and MBRassociated transcriptional changes across hippocampus, amygdala, and blood. The sex-specific mechanisms involved in EBR may contribute to the pronounced disparity in risk for PTSD, with women much more likely to develop PTSD.

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“…PTSD poses a considerable public health concern because of the debilitating nature of the symptoms and because of the high rates of comorbidity with other psychiatric disorders such as major depression and bipolar disorder [10]. People with PTSD also experience chronic inflammation [11••], metabolic disorder [12], increased incidence of coronary artery disease [13, 14], and increased rates of early mortality [8, 15]. …”

Section: Introductionmentioning

confidence: 99%

Molecular and Cellular Effects of Traumatic Stress: Implications for PTSD

Girgenti

Hare

Ghosal

et al. 2017

Curr Psychiatry Rep

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Purpose of Review Posttraumatic stress disorder (PTSD) is characterized by hyperarousal and recurrent stressful memories after an emotionally traumatic event. Extensive research has been conducted to identify the neurobiological determinants that underlie the pathophysiology of PTSD. In this review, we examine evidence regarding the molecular and cellular pathophysiology of PTSD focusing on two primary brain regions: the vmPFC and the amygdala. Recent Findings This discussion includes a review of the molecular alterations related to PTSD, focusing mainly on changes to glucocorticoid receptor signaling. We also examine postmortem gene expression studies that have been conducted to date and the molecular changes that have been observed in peripheral blood studies of PTSD patients. Causal, mechanistic evidence is difficult to obtain in human studies, so we also review preclinical models of PTSD. Summary Integration of peripheral blood and postmortem studies with preclinical models of PTSD has begun to reveal the molecular changes occurring in patients with PTSD. These findings indicate that the pathophysiology of PTSD includes disruption of glucocorticoid signaling and inflammatory systems and occurs at the level of altered gene expression. We will assess the impact of these findings on the future of PTSD molecular research.

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Traumatic Stress and Accelerated Cellular Aging: From Epigenetics to Cardiometabolic Disease

Cited by 59 publications

References 105 publications

Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood

Molecular and Cellular Effects of Traumatic Stress: Implications for PTSD

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