DNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma

Marinova, Zoya; Maercker, Andreas; Küffer, Andreas; Robinson, Mark D.; Wojdacz, Tomasz K.; Walitza, Susanne; Grünblatt, Edna; Burri, Andrea

doi:10.1186/s12881-017-0370-2

Cited by 27 publications

(23 citation statements)

References 47 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finding that Dlx5/6 are also important in determining healthspan and lifespan lead us to suggest that they might play an important role in establishing a fecundity/lifespan tradeoff during evolution. In this respect it is important to note that the methylation level of DLX5/6 increases in response to aging (43), metabolism (74) and life exposures (76) suggesting that these genes might be integrators of lifespan determinants. B) The quality of nests built by control, Vgat ∆Dlx5-6/+ and Vgat ∆Dlx5-6 mice was evaluated each day over a seven days period.…”

Section: Discussionmentioning

confidence: 99%

Dlx5andDlx6expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan

Lombares

Heude

Alfama

et al. 2019

Preprint

View full text Add to dashboard Cite

Dlx5 and Dlx6 encode two homeobox transcription factors expressed by developing and mature GABAergic interneurons. During development Dlx5/6 are important for the differentiation of Parvalbumin (Pvalb)-expressing neurons. Perinatal lethality of homozygous mice in which Dlx5/6 have been constitutively deleted has, so far, hindered the study of the function of these genes in adult neurons. We first show that Dlx5 and Dlx6 are expressed by all subclasses of adult cortical GABAergic neurons. Then we analyse VgatΔDlx5-6 mice in which Dlx5 and Dlx6 are simultaneously inactivated in all GABAergic interneurons. VgatΔDlx5-6 mice present a behavioral pattern suggesting reduction of anxiety and obsessive-compulsive activities. They rapidly access and spend more time in the central region of an open field, bury few marbles in the marble burying test and show little interest in nest building. Male and female 20-month-old VgatΔDlx5-6 animals have the same size as their normal littermates, but present a 25% body weight reduction associated with a marked decline in white and brown adipose tissue. Remarkably, both VgatΔDlx5-6/+ and VgatΔDlx5-6 mice present a 33% longer median survival than their control littermates. Hallmarks of biological aging such as motility, adipose deposition and coat conditions are improved in mutant animals. Our data imply that GABAergic interneurons can regulate mammalian healthspan and lifespan through Dlx5/6-dependent mechanisms. Understanding these regulations can be an entry point to unravel the processes through which the brain affects body homeostasis and, ultimately, longevity and healthy aging.SIGNIFICANCE STATEMENTDlx5 and Dlx6 are transcription factors controlling several developmental processes, including GABAergic neuronal migration and differentiation. To study their function in adult brain, we selectively inactivated both genes in GABAergic interneurons (VgatΔDlx5-6 mice). Mutant mice have reduced anxiety-like and obsessive-compulsive behaviors. Interestingly, VgatΔDlx5-6 mice have a 25% body weight reduction and about 70% less white and brown adipose tissue; their general health status is excellent. VgatΔDlx5-6 mice have a median survival about 33% longer than their control littermates and hallmarks of biological aging are improved. Dlx5/6-dependent regulations in GABAergic neurons could be an entry point to understand how the brain determines the psychophysiological status of the body and, ultimately, longevity and healthy aging.

show abstract

Section: Discussionmentioning

confidence: 99%

Dlx5andDlx6expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan

Lombares

Heude

Alfama

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, a cross-sectional study by Zhang et al [34] studied 82 candidate genes in 518 individuals and found that exposure to childhood abuse in European-Americans was associated with differential methylation in both subjects with ethanol dependence and controls, while no site was differentially methylated in African-Americans. In a group of former child labourers, 71 differentially methylated CpGs were found [35].…”

Section: Genome-wide Association Studiesmentioning

confidence: 99%

“…Of the nine genome-wide association studies, five articles utilized a common method (Illumina HumanMethylation450 BeadChip) to analyse DNA methylation across the genome, which made them eligible for inclusion in a meta-analysis of genome-wide association studies [31,32,[35][36][37]. Cecil et al [36] kindly made summary data from their study available, and discovery data from Houtepen et al [37] were accessed from the GEO data repository (GEO Accession Number: GSE77445).…”

Section: Meta-analysis Of Genome-wide Association Studiesmentioning

confidence: 99%

Epigenomic mediation after adverse childhood experiences: a systematic review and meta-analysis

Neves

Dinis-Oliveira

Magalhães

2019

Forensic Sciences Research

View full text Add to dashboard Cite

Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment, leading to changes in the regulation of multiple organ systems. This study was established to review the epigenetic mechanisms associated with childhood abuse as well as the long-term determinants that these epigenetic changes may have on future illness. We retrospectively analysed the effect of exposure to adverse childhood experiences (ACEs, specifically those relating to childhood maltreatment) between the ages of 0 and 16 years on the human epigenome, as well as possible clinical associations. After meeting inclusion and exclusion criteria, 36 articles were included in this systematic review. Eight of these studies did not find a relationship between childhood maltreatment and DNA methylation. Of the remaining 28 studies, nine were genome-wide association studies, whereas the rest were candidate-gene studies, mainly studying effects on neuroendocrine, serotoninergic and immunoregulatory systems. Meta-analysis of correlation coefficients from candidate gene studies estimated an association of childhood adversity and DNA methylation variation at r ¼ 0.291 (P < 0.0001), and meta-analysis of two epigenome-wide association studies (EWASs) identified 44 differentially methylated CpG sites. In conclusion, childhood maltreatment may mediate epigenetic mechanisms through DNA methylation, thereby affecting physiological responses and conferring a predisposition to an increased risk for psychopathology and forensic repercussions. Similar evidence for somatic illnesses is not yet available. KEY POINTS Adverse childhood experiences are associated with increased mortality partly explained by acquired epigenetic changes There is a positive correlation between childhood abuse and DNA methylation at specific gene sites The cumulative effect of different types of childhood abuse and neglect may lead to changes in DNA methylation Epigenome changes associated with childhood abuse appear to be involved in the development of psychiatric illness in adulthood Studying epigenetic changes may have important public health and forensic applications in the future ARTICLE HISTORY

show abstract

“…Although a substantial body of research has accumulated linking early-life adversity to differences in DNA methylation, methods and results are heterogeneous and nonoverlapping. Under the label of “adversity,” studies have focused on a diverse mix of exposures spanning maternal psychiatric disease (13), early parental loss (14), institutionalization (15), indentured child labor (16), child abuse (17), and the Holocaust (18). On the outcome side, DNA methylation differences in surrogate tissue, such as whole blood, have been reported, but often in different genomic regions.…”

mentioning

confidence: 99%

Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood

Marzi

Sugden

Arseneault

et al. 2018

AJP

120

100

View full text Add to dashboard Cite

Objective DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become “embedded” in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation. Method The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994–1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime). Results Epigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes. Conclusions Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress.

show abstract

DNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma

Cited by 27 publications

References 47 publications

Dlx5andDlx6expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan

Dlx5andDlx6expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan

Epigenomic mediation after adverse childhood experiences: a systematic review and meta-analysis

Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood

Contact Info

Product

Resources

About