The Cellular Sequelae of Early Stress: Focus on Aging and Mitochondria

Ridout, Kathryn K.; Carpenter, Linda L.; Tyrka, Audrey R.

doi:10.1038/npp.2015.301

Cited by 15 publications

(15 citation statements)

References 6 publications

(14 reference statements)

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“…Telomeres shorten after repeated cellular divisions and cellular stress exposures 70 . It has been speculated that early adversity directly activates or is associated with increased cellular stress and replication, resulting in accelerated telomere shortening 8, 17 . Telomerase activity, a key regulator of telomere length, is decreased with adversity exposure 71 .…”

Section: Discussionmentioning

confidence: 99%

“…Many chronic illnesses involve prolonged states of stress and/or inflammation, which may contribute associations between telomere length and somatic conditions, including heart disease, diabetes, asthma, obesity, chronic pain, irritable bowel syndrome, and neurodegenerative disorders 11, 13–16 . Proposed mechanisms underlying associations between stress and telomere length include mitochondrial dysfunction and telomerase inactivation due to heightened and prolonged stress signaling 9, 17, 18 . In addition to reflecting biologic stress, telomere attrition often precedes chronic disease development, suggesting that telomere erosion may be a causal link connecting early adversity and later disease 12 .…”

Section: Introductionmentioning

confidence: 99%

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Early life adversity and telomere length: a meta-analysis

et al. 2017

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Early adversity, in the form of abuse, neglect, socioeconomic status, and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regards to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing, and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO, and Web of Science identified 2 462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data was extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N =30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen’s d effect size = −0.35; 95% CI, –0.46 to –0.24, p < 0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (p < .0001 and p = .0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control versus longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early life adversity and telomere length: a meta-analysis

et al. 2017

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“…[16] These hormones rapidly signal multiple physiological changes, including increasing heart rate and blood pressure, splanchnic vasoconstriction, muscle vasodilation, and bronchodilation. [18] This stress response in the short-term is vital for survival, but its adaptability is conditional on its efficient termination facilitated by cortisol via a negative feedback loop. [16] Cortisol, with its array of downstream effects, chiefly promotes glucose production to supply the energy necessary to respond to the stress.…”

Section: Adverse Childhood Experiences Are a Form Of Toxic Early Lifementioning

confidence: 99%

“…[16] The HPA-axis responds more slowly to the stressful stimulus and concludes with the release of glucocorticoids, namely cortisol, from the adrenal cortex. [18,19] Chronic activation of the stress response due to toxic stress exposure dysregulates the HPA-axis in the long-term, eventually leading to dysfunction across multiple physiological systems. [18] This stress response in the short-term is vital for survival, but its adaptability is conditional on its efficient termination facilitated by cortisol via a negative feedback loop.…”

Section: Adverse Childhood Experiences Are a Form Of Toxic Early Lifementioning

confidence: 99%

“…[23] Prolonged activation of the stress response following toxic stress exposure perturbs the immune and metabolic systems as demonstrated by the clustering of inflammatory and metabolic risk factors for stress-related disease observed in adults with ELS histories. [17,18,24] As a consequence of increased glucocorticoid secretion during a chronic stress response, elevated glucose levels alter mitochondrial morphology by promoting excessive mitochondrial fragmentation, thereby increasing reactive oxygen species (ROS) production. [17,18,24] As a consequence of increased glucocorticoid secretion during a chronic stress response, elevated glucose levels alter mitochondrial morphology by promoting excessive mitochondrial fragmentation, thereby increasing reactive oxygen species (ROS) production.…”

Section: Increased Allostatic Load May Link Toxic Stress To Health Oumentioning

confidence: 99%

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Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress

2018

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This manuscript reviews recent evidence supporting the utility of telomeres and mitochondrial DNA copy number (mtDNAcn) in detecting the biological impacts of adverse childhood experiences (ACEs) and outlines mechanisms that may mediate the connection between early stress and poor physical and mental health. Critical to interrupting the health sequelae of ACEs such as abuse, neglect, and neighborhood disorder, is the discovery of biomarkers of risk and resilience. The molecular markers of chronic stress exposure, telomere length and mtDNAcn, represent critical biological links between ACEs and poor health outcomes. We examine how telomeres and mtDNAcn may exacerbate health disparities and contribute to the intergenerational transmission of trauma. Finally, we explore how these molecular markers of early stress exposure may help define the role of resilience and develop effective interventions to moderate ACE health risk impact.

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Physician-Training Stress and Accelerated Cellular Aging

Ridout

Guille

et al. 2019

Biological Psychiatry

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The Cellular Sequelae of Early Stress: Focus on Aging and Mitochondria

Cited by 15 publications

References 6 publications

Early life adversity and telomere length: a meta-analysis

Early life adversity and telomere length: a meta-analysis

Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress

Physician-Training Stress and Accelerated Cellular Aging

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