Epigenetic drift in aging identical twins

Martin, George M.

doi:10.1073/pnas.0504743102

Cited by 172 publications

(126 citation statements)

References 17 publications

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“…Based on these early studies, it was hypothesized that DNA methylation was not accurately maintained over cell divisions, resulting in a gradual loss and increase in variability over the lifespan (Cooney, 1993). This phenomenon has been referred to as ‘epigenetic drift’ (Egger et al ., 2004; Martin, 2005). More recent work has shown that both Alu and LINE‐1 repetitive elements exhibit decreased DNA methylation levels and increased variability with age (Bollati et al ., 2009; Talens et al ., 2012).…”

Section: Dna Methylation Dynamics During Agingmentioning

confidence: 99%

“…Microarray studies confirmed a decrease in DNA methylation with age, while site‐specific analysis indicated an increase in variability of DNA methylation with age. The latter was first noted in monozygotic twins, and subsequently in unrelated individuals (Fraga et al ., 2005; Martin, 2005; Poulsen et al ., 2007; Kaminsky et al ., 2009; Martino et al ., 2011). These studies also supported the idea that DNA methylation showed reduced stringency in maintenance over the lifespan, resulting in an increase in interindividual variability along with the overall decrease in DNA methylation.…”

Section: Dna Methylation Dynamics During Agingmentioning

confidence: 99%

“…In addition to the environmental signatures, DNA methylation changes with no obvious cause or pattern have been observed and ascribed to the reduced capability of faithfully maintaining epigenetic marks over cell divisions (Fraga et al ., 2005; Martin, 2005). Changes in the functionality of epigenetic machinery in addition to exposure of the genome to environmental factors might therefore also contribute to increasing epigenetic diversity with age (Fraga & Esteller, 2007).…”

Section: Epigenetic Drift Vs the Epigenetic Clock: Two Phenomena Undmentioning

confidence: 99%

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DNA methylation and healthy human aging

2015

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SummaryThe process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next‐generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site‐specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age‐related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining ‘epigenetic age’ for human health and outline some important caveats to existing and future studies.

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Section: Dna Methylation Dynamics During Agingmentioning

confidence: 99%

Section: Dna Methylation Dynamics During Agingmentioning

confidence: 99%

Section: Epigenetic Drift Vs the Epigenetic Clock: Two Phenomena Undmentioning

confidence: 99%

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DNA methylation and healthy human aging

2015

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“…The DNA methylation profile is heritable through mitosis, but the fidelity of this transmission is imperfect (Bennett-Baker et al 2003) and may contribute to differences in gene expression and phenotype observed between genetically identical individuals, whether isogenic strains of mice (Gartner and Baunack 1981;Pritchard et al 2006) or human MZ twins (Fraga et al 2005;Martin 2005;Kuratomi et al 2008;Kaminsky et al 2009;Javierre et al 2010).…”

mentioning

confidence: 99%

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

Gordon¹,

Joo²,

Powell³

et al. 2012

Genome Res.

258

216

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Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of~20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.

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“…Reliance on leukocyte DNA extracted from peripheral blood introduces a potential source of measurement error [66]. Given the labile nature of leukocyte subtype populations over time, this variation may make an important contribution to intra-individual changes in DNA methylation.…”

Section: The Epidemiological Toolkitmentioning

confidence: 99%