Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

Jaime Madrigano; Andrea Baccarelli; Murray A. Mittleman; David Sparrow; Pantel S. Vokonas; Letizia Tarantini; Joel Schwartz

doi:10.4161/epi.7.1.18749

Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

Jaime Madrigano, Andrea Baccarelli, Murray A. Mittleman, David Sparrow, Pantel S. Vokonas, Letizia Tarantini, Joel Schwartz

Research output: Contribution to journal › Article › peer-review

Abstract

DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 1999-2009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFNγ, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFNγ (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFNγ was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging.

Original language	English (US)
Pages (from-to)	63-70
Number of pages	8
Journal	Epigenetics
Volume	7
Issue number	1
DOIs	https://doi.org/10.4161/epi.7.1.18749
State	Published - Jan 2012
Externally published	Yes

Keywords

Aging
DNA methylation
Epigenesis
Genetic

ASJC Scopus subject areas

Molecular Biology
Cancer Research

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10.4161/epi.7.1.18749

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title = "Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation",

abstract = "DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 1999-2009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFNγ, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFNγ (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFNγ was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging.",

keywords = "Aging, DNA methylation, Epigenesis, Genetic",

author = "Jaime Madrigano and Andrea Baccarelli and Mittleman, {Murray A.} and David Sparrow and Vokonas, {Pantel S.} and Letizia Tarantini and Joel Schwartz",

note = "Funding Information: This work was supported by the National Institue of Environmental Health Sciences at the National Institutes of Health (T32ES07069, ES0002, ES015172-01, ES014663 and T32ES016645). The VA NAS is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA.",

year = "2012",

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doi = "10.4161/epi.7.1.18749",

language = "English (US)",

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AU - Madrigano, Jaime

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AU - Sparrow, David

AU - Vokonas, Pantel S.

AU - Tarantini, Letizia

AU - Schwartz, Joel

N1 - Funding Information: This work was supported by the National Institue of Environmental Health Sciences at the National Institutes of Health (T32ES07069, ES0002, ES015172-01, ES014663 and T32ES016645). The VA NAS is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA.

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N2 - DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 1999-2009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFNγ, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFNγ (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFNγ was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging.

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Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

Abstract

Keywords

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