Epigenetic aging: insights from network biology

Teschendorff, Andrew E.

doi:10.18632/aging.100610

Cited by 7 publications

(5 citation statements)

References 6 publications

(8 reference statements)

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“…Across the life span, environmental and stochastic changes accumulate in DNAm throughout the genome and across tissues, and are believed to contribute to increasing diversity over time (Teschendorff, 2013). Well-powered studies assessing the DNAm landscape across the genome have identified normative patterns of cell changes associated with age (Teschendorff, West, & Beck, 2013).…”

Section: Dnam and The Epigenetic Clockmentioning

confidence: 99%

Epigenetic correlates of neonatal contact in humans

et al. 2017

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Animal models of early postnatal mother-infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4-5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.

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Section: Dnam and The Epigenetic Clockmentioning

confidence: 99%

Epigenetic correlates of neonatal contact in humans

et al. 2017

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“…DNA methylation patterns are shaped by two opposing processes of adding and removing a methyl group at position five of cytosine in DNA [ 12 ]. Age-associated alterations in DNA methylation are commonly grouped into a phenomenon known as “epigenetic drift,” which is characterized by gradual extensive demethylation of the genome and hypermethylation of a number of promoter-associated CpG islands [ 13 - 15 ]. Hypermethylation of CpG islands in gene promoters induces gene silencing and alters gene expression.…”

Section: Introductionmentioning

confidence: 99%

Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells

Wang

Chen

2016

Oncotarget

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Aging is an inevitable part of life for humans, and slowing down the aging process has become a main focus of human endeavor. Here, we applied a systems biology approach to construct protein-protein interaction networks, gene regulatory networks, and epigenetic networks, i.e. genetic and epigenetic networks (GENs), of elderly individuals and young controls. We then compared these GENs to extract aging mechanisms using microarray data in peripheral blood mononuclear cells, microRNA (miRNA) data, and database mining.The core GENs of elderly individuals and young controls were obtained by applying principal network projection to GENs based on Principal Component Analysis. By comparing the core networks, we identified that to overcome the accumulated mutation of genes in the aging process the transcription factor JUN can be activated by stress signals, including the MAPK signaling, T-cell receptor signaling, and neurotrophin signaling pathways through DNA methylation of BTG3, G0S2, and AP2B1 and the regulations of mir-223 let-7d, and mir-130a. We also address the aging mechanisms in old men and women. Furthermore, we proposed that drugs designed to target these DNA methylated genes or miRNAs may delay aging. A multiple drug combination comprising phenylalanine, cholesterol, and palbociclib was finally designed for delaying the aging process.

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“…De-regulation of DNA methylation can increase the susceptibility to chronic diseases like CVD. Furthermore, it has been hypothesised that a healthy lifestyle may reserve a more intact epigenome, promoting longevity [15]. In a recent compelling study by Horvath and colleagues, a novel, sensitive and highly robust DNAm age estimator (based on 391 CpGs) was developed for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood and saliva samples [16].…”

Section: Epigeneticsmentioning

confidence: 99%

Platelets: Functional Biomarkers of Epigenetic Drift

Twomey¹,

Wallace²,

Mangone³

et al. 2019

Homeostasis - An Integrated Vision

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Cardiovascular disease (CVD) risk factors can be classed as modifiable or non-modifiable. Physical inactivity and obesity represent major behavioural risk factors for the initiation, development and progression of CVD. Platelet dysfunction is pivotal to the aetiology of CVD, a chronic vascular inflammatory condition, which is characterised by a lag time between onset and clinical manifestation. This indicates the role of epigenetic drift, defined by stochastic patterns of gene expression not dependent on dynamic changes in coding DNA. The epigenome, a collection of chemical marks on DNA and histones, is established during embryogenesis and modified by age and lifestyle. Biogenesis and effector function of non-coding RNA, such as microRNA, play a regulatory role in gene expression and thus the epigenetic mechanism. In this chapter, we will focus on the effect of the modifiable risk factors of physical activity/inactivity and overweight/obesity on platelet function, via epigenetic changes in both megakaryocytopoiesis and thrombopoiesis. We will also discuss the role of acute exercise on platelet function and the impact of cardiorespiratory fitness (CRF) on platelet responses to acute exercise. This chapter will highlight the potential role of platelets as circulating functional biomarkers of epigenetic drift to implement, optimise and monitor CVD preventive management strategies.

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Epigenetic aging: insights from network biology

Cited by 7 publications

References 6 publications

Epigenetic correlates of neonatal contact in humans

Epigenetic correlates of neonatal contact in humans

Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells

Platelets: Functional Biomarkers of Epigenetic Drift

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