Childhood location correlates with epigenetic age and methylation stability in British-Bangladeshi migrants

AbstractBackgroundMigration from one environment to another often causes marked changes in developmental conditions. Here we compare epigenetic ageing and stability of the epigenetic maintenance system among British-Bangladeshi women who grew up in Bangladesh (adult migrants), where there are higher pathogen loads and poorer health care, to second-generation Bangladeshis who grew up in the UK. In our previous studies of these migrants, those who spent their childhoods in Bangladesh also had lower levels of reproductive hormones and a shorter reproductive lifespan compared to those who grew up in the UK, suggesting life history trade-offs during development. In the present study, we hypothesised that women who grew up in Bangladesh would have i) an older epigenetic/biological age compared to the women with a childhood in the UK and ii) that differences in the pace of epigenetic ageing might also be reflected by altered stability of DNA methylation marks.ResultsIllumina EPIC array methylation data from buccal tissue was used to establish epigenetic age estimates from 15 adult migrants and 11 second-generation migrants, aged 18-35 years. Using residuals from linear regression of DNA methylation-based biological age (DNAm age) on the chronological age, the results showed significant differences (p=0.016) in epigenetic age estimates: women whose childhood was in Bangladesh are on average 6.02 (± 2.34) years older, than those who grew up in London. We further investigated the efficiency of the epigenetic maintenance system which purportedly is reflected by epigenetic clocks. Methylation states of CpGs at the LHCGR/LHR locus, which contributes to Horvath’s multi tissue epigenetic clock were evaluated. Based on the Ratio of Concordance Preference (RCP) approach that uses double-stranded methylation data, we find that maintenance of epigenetic information is more stable in women who grew up in Bangladesh.ConclusionsThe work supports earlier findings that adverse childhood environments lead to phenotypic life history trade-offs. The data indicate that childhood environments can induce subtle changes to the epigenetic maintenance system that are detectable long after exposure occurred. The implication of such a finding warrants further investigation as it implies that a less flexible epigenetic memory system established early in life could reduce the capacity to respond to different environmental conditions in adult life.

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DEVELOPMENT OF EPIGENETIC MEASURES FOR GEROSCIENCE CLINICAL TRIALS

Innovation in Aging ◽

10.1093/geroni/igz038.2732 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S746-S746

Author(s):

Morgan E Levine

Keyword(s):

Dna Methylation ◽

Clinical Trials ◽

Surrogate Endpoints ◽

Methylation Data ◽

Biomarkers Of Aging ◽

Age Related ◽

Epigenetic Age ◽

Human And Mouse ◽

Promising Avenue

Abstract One of the major goals of the NIA is to oversee development of biomarkers of aging. In recent years, DNA methylation has emerged as a promising avenue from which to quantify biological age. We and others have shown that these measures track age across various tissues and cells, and further deviations between chronological and “epigenetic age” have been shown to confer risk for various aging outcomes. However, the usefulness of these measures will depend on both their modifiability and ability to capture known targetable hallmarks of aging. Using DNA methylation data from cell line experiments, we have recently generated epigenetic predictors of cellular senescence for both human and mouse that when assessed in vivo from bulk samples, show age-related increases and are associated with aging outcomes. In moving forward, measures such as these may serve as promising surrogate endpoints for assessing efficacy of senolytic drugs and/or other anti-aging therapeutics.

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Epigenetic Control of Temperature-Dependent Female Reproductive Life History Trade-Offs in Seed Beetles, Callosobruchus maculatus

10.1101/2021.10.08.463711 ◽

2021 ◽

Author(s):

Beth Anne McCaw ◽

Aoife M Leonard ◽

Tyler J Stevenson ◽

Lesley T Lancaster

Keyword(s):

Dna Methylation ◽

Life History ◽

Callosobruchus Maculatus ◽

Global Environmental Change ◽

The Body ◽

Temperature Dependent ◽

Trade Offs ◽

Reproductive Life ◽

Seed Beetles ◽

Reproductive Life History

Many species are threatened by climate change and must rapidly respond to survive changing environments. Epigenetic modifications, such as DNA methylation, can facilitate plastic responses by regulating gene expression in response to environmental cues. Understanding epigenetic responses is therefore essential for predicting species’ ability to rapidly adapt in the context of global environmental change. Here, we investigated the functional significance of DNA methylation on temperature-dependent life history in seed beetles, Callosobruchus maculatus. We assessed changes in DNA methyltransferase (Dnmt1 and Dnmt2) expression levels under ambient conditions and thermal stress, and reproductive performance following artificially-induced epimutation via 3-aminobenzamide (3AB) and Zebularine (Zeb), at a range of ambient and warmer temperatures over two generations. We found that Dnmt1 and Dnmt2 were greatly expressed in females, throughout the body, and exhibited temperature-dependence; in contrast, Dnmt expression was minimal in males. Epimutation led to shifts in female reproductive life history trade-off allocation, and differentially altered thermal optima of fecundity and offspring viability. This study revealed the optimal allocation strategy among these fitness components is temperature-dependent, and trade-offs become increasingly difficult to resolve epigenetically under more extreme warming. Results suggest that epigenetic mechanisms are strongly implicated in, and perhaps limiting of, invertebrate life history responses to temperature change. Further investigation will reveal targeted DNA methylation patterns and specific loci associated with temperature-dependent life history trade-offs in seed beetles and other invertebrates.

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Different epigenetic clocks reflect distinct pathophysiological features of multiple sclerosis

Epigenomics ◽

10.2217/epi-2019-0102 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1429-1439 ◽

Cited By ~ 1

Author(s):

Eleftheria Theodoropoulou ◽

Lars Alfredsson ◽

Fredrik Piehl ◽

Francesco Marabita ◽

Maja Jagodic

Keyword(s):

Multiple Sclerosis ◽

Dna Methylation ◽

Positive Association ◽

Cell Types ◽

Gene Expression Omnibus ◽

Methylation Data ◽

Accession Number ◽

Age Related ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

Aim: Accumulating evidence links epigenetic age to diseases and age-related conditions, but little is known about its association with multiple sclerosis (MS). Materials & methods: We estimated epigenetic age acceleration measures using DNA methylation from blood or sorted cells of MS patients and controls. Results: In blood, sex (p = 4.39E-05) and MS (p = 2.99E-03) explained the variation in age acceleration, and isolated blood cell types showed different epigenetic age. Intrinsic epigenetic age acceleration and extrinsic epigenetic age acceleration were only associated with sex (p = 2.52E-03 and p = 1.58E-04, respectively), while PhenoAge Acceleration displayed positive association with MS (p = 3.40E-02). Conclusion: Different age acceleration measures are distinctly influenced by phenotypic factors, and they might measure separate pathophysiological aspects of MS. Data deposition: DNA methylation data can be accessed at Gene Expression Omnibus database under accession number GSE35069, GSE43976, GSE106648, GSE130029, GSE130030.

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DNA methylation age analysis of rapamycin in common marmosets

10.1101/2020.11.21.392779 ◽

2020 ◽

Cited By ~ 1

Author(s):

Steve Horvath ◽

Joseph A. Zoller ◽

Amin Haghani ◽

Ake T. Lu ◽

Ken Raj ◽

...

Keyword(s):

Dna Methylation ◽

Rhesus Macaques ◽

Common Marmoset ◽

Primate Species ◽

Vervet Monkeys ◽

Methylation Data ◽

Common Marmosets ◽

Biomarkers Of Aging ◽

Epigenetic Age ◽

The Common

AbstractHuman DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here, two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

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Epigenetic clock detected a breast cancer mitosis subtype with improved immunotherapy

10.21203/rs.3.rs-196073/v1 ◽

2021 ◽

Author(s):

Shipeng Shang ◽

Xin Li ◽

Yue Gao ◽

Shuang Guo ◽

Hanxiao Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Breast Tissue ◽

Pearson Correlation ◽

Breast Cancer Subtypes ◽

Chronological Age ◽

Epigenetic Clock ◽

Methylation Data ◽

Cancer Subtypes ◽

Epigenetic Age

Abstract Background Epigenetic clock based on DNA methylation can estimate the epigenetic age of tissue and cell that can describe the process of aging. However, the exploration of diseases by the epigenetic clock is still an uncharted territory. Our objective was to assess the role of the epigenetic clock in breast cancer. Methods In this study, DNA methylation data of breast tissue sample was download from TCGA and GEO database. DNA methylation level of CpG sites and age of samples was calculated by using pearson correlation test. Differentially expressed genes were identified using the limma package and Kruskal-Wallis test was used for the difference between cancer subtypes. Results We developed a workflow to construct the Breast Epigenetic Clock (BEpiC) that could accurately predict the chronological age of normal breast tissue. Furthermore, the BEpiC was applied to breast cancer to identify three breast cancer subtypes (including development, homeostasis, and mitosis) by using the deviation between epigenetic age and chronological age. Interestingly, the prognosis of the three breast cancer subtypes is significantly different. In addition, the three breast cancer subtypes had distinct differences in multiple immune cells and the mitosis subtype had the highest tumor mutation burden that was used to estimate response to checkpoint inhibitors. Conclusion Our model highlights that epigenetic age of breast cancer samples had an important impact on immunotherapy. We constructed a BEpiC web server (http://bio-bigdata.hrbmu.edu.cn/BEpiC/) where users submit DNA methylation data and age information to predict the epigenetic age of breast tissue and breast cancer subtypes. Trial registration Not applicable

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DNA methylation age analysis of rapamycin in common marmosets

GeroScience ◽

10.1007/s11357-021-00438-7 ◽

2021 ◽

Author(s):

Steve Horvath ◽

Joseph A. Zoller ◽

Amin Haghani ◽

Ake T. Lu ◽

Ken Raj ◽

...

Keyword(s):

Dna Methylation ◽

Rhesus Macaques ◽

Common Marmoset ◽

Primate Species ◽

Vervet Monkeys ◽

Methylation Data ◽

Common Marmosets ◽

Biomarkers Of Aging ◽

Epigenetic Age ◽

The Common

AbstractHuman DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

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Experimentally increased costs of parental care are shunted to offspring in species with extended care

10.32942/osf.io/y8wx4 ◽

2019 ◽

Author(s):

Gretchen F. Wagner ◽

Emeline Mourocq ◽

Michael Griesser

Keyword(s):

Life History ◽

Parental Care ◽

Total Duration ◽

Bird Species ◽

Life History Strategy ◽

Experimental Treatment ◽

Cost Of Care ◽

Adult Survival ◽

Supporting Evidence ◽

Trade Offs

Biparental care systems are a valuable model to examine conflict, cooperation, and coordination between unrelated individuals, as the product of the interactions between the parents influences the fitness of both individuals. A common experimental technique for testing coordinated responses to changes in the costs of parental care is to temporarily handicap one parent, inducing a higher cost of providing care. However, dissimilarity in experimental designs of these studies has hindered interspecific comparisons of the patterns of cost distribution between parents and offspring. Here we apply a comparative experimental approach by handicapping a parent at nests of five bird species using the same experimental treatment. In some species, a decrease in care by a handicapped parent was compensated by its partner, while in others the increased costs of care were shunted to the offspring. Parental responses to an increased cost of care primarily depended on the total duration of care that offspring require. However, life history pace (i.e., adult survival and fecundity) did not influence parental decisions when faced with a higher cost of caring. Our study highlights that a greater attention to intergenerational trade-offs is warranted, particularly in species with a large burden of parental care. Moreover, we demonstrate that parental care decisions may be weighed more against physiological workload constraints than against future prospects of reproduction, supporting evidence that avian species may devote comparable amounts of energy into survival, regardless of life history strategy.

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Telling Diaspora Stories: theoretical and methodological reflections on narratives of migrancy and belongingness in the second generation

MIGRATION LETTERS ◽

10.33182/ml.v6i2.73 ◽

2009 ◽

Vol 6 (2) ◽

pp. 143-153 ◽

Cited By ~ 11

Author(s):

Anastasia Christou

Keyword(s):

Life History ◽

Second Generation ◽

Life Stories ◽

Narrative Research ◽

Social Experiences ◽

Biographical Approach ◽

The Subject

This article explores the theoretical and methodological implications of the study of second generation migration through the use of life stories, a narrative and biographical approach. It presents a theoretical contextualisation of life history research in addressing the direction it has taken in the study of migration and identity in order to problematise how the subject and subjectivities in narrative research have been framed by social categorisations such as gender, ethnicity, class as well as social experiences such as trauma, exile, memory and imagination. The paper develops the analytical contribution of researching the biographicity of everyday migrant lives.

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Independent commissions and labour migration: The British MAC

MIGRATION LETTERS ◽

10.33182/ml.v11i1.167 ◽

2014 ◽

Vol 11 (1) ◽

pp. 23-32

Author(s):

Philip L. Martin ◽

Martin Ruhs

Keyword(s):

Labour Force ◽

Migration Policy ◽

Foreign Workers ◽

Foreign Born ◽

Independent Evidence ◽

Trade Offs ◽

Labour Immigration ◽

British Labour ◽

Policy Objectives ◽

The Uk

The independent Migration Advisory Committee (MAC) was created in 2007 after a decade in which the share of foreign-born workers in the British labour force doubled to 13 per cent. The initial core mandate of the MAC was to provide “independent, evidence-based advice to government on specific skilled occupations in the labour market where shortages exist which can sensibly be filled by migration.” The MAC's answers to these 3-S questions, viz, is the occupation for which employers are requesting foreign workers skilled, are there labour shortages, and is admitting foreign workers a sensible response, have improved the quality of the debate over the “need” for foreign workers in the UK by highlighting some of the important trade-offs inherent in migration policy making. The MAC can clarify migration trade-offs in labour immigration policy, but cannot decide the ultimately political questions about whose interests should be prioritised and how competing policy objectives should be balanced.

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