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Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation.

ABSTRACT: Low socioeconomic status (SES) is associated with earlier onset of age-related chronic conditions and reduced life-expectancy, but the underlying biomolecular mechanisms remain unclear. Evidence of DNA-methylation differences by SES suggests a possible association of SES with epigenetic age acceleration (AA). We investigated the association of SES with AA in more than 5,000 individuals belonging to three independent prospective cohorts from Italy, Australia, and Ireland. Low SES was associated with greater AA (??=?0.99 years; 95% CI 0.39,1.59; p?=?0.002; comparing extreme categories). The results were consistent across different SES indicators. The associations were only partially modulated by the unhealthy lifestyle habits of individuals with lower SES. Individuals who experienced life-course SES improvement had intermediate AA compared to extreme SES categories, suggesting reversibility of the effect and supporting the relative importance of the early childhood social environment. Socioeconomic adversity is associated with accelerated epigenetic aging, implicating biomolecular mechanisms that may link SES to age-related diseases and longevity.

SUBMITTER: Fiorito G

PROVIDER: S-EPMC5701128 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation.

Fiorito Giovanni G Polidoro Silvia S Dugué Pierre-Antoine PA Kivimaki Mika M Ponzi Erica E Matullo Giuseppe G Guarrera Simonetta S Assumma Manuela B MB Georgiadis Panagiotis P Kyrtopoulos Soterios A SA Krogh Vittorio V Palli Domenico D Panico Salvatore S Sacerdote Carlotta C Tumino Rosario R Chadeau-Hyam Marc M Stringhini Silvia S Severi Gianluca G Hodge Allison M AM Giles Graham G GG Marioni Riccardo R Karlsson Linnér Richard R O'Halloran Aisling M AM Kenny Rose A RA Layte Richard R Baglietto Laura L Robinson Oliver O McCrory Cathal C Milne Roger L RL Vineis Paolo P

Scientific reports 20171124 1

Low socioeconomic status (SES) is associated with earlier onset of age-related chronic conditions and reduced life-expectancy, but the underlying biomolecular mechanisms remain unclear. Evidence of DNA-methylation differences by SES suggests a possible association of SES with epigenetic age acceleration (AA). We investigated the association of SES with AA in more than 5,000 individuals belonging to three independent prospective cohorts from Italy, Australia, and Ireland. Low SES was associated w ...[more]

PMID: 29176660

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Project description:BackgroundAlzheimer's disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized that the disease-associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs.ResultsComparison of 23 disease discordant Finnish twin pairs with reduced representation bisulfite sequencing revealed peripheral blood DNA methylation differences in 11 genomic regions with at least 15.0% median methylation difference and FDR adjusted p value ≤ 0.05. Several of the affected genes are primarily associated with neuronal functions and pathologies and do not display disease-associated differences in gene expression in blood. The DNA methylation mark in ADARB2 gene was found to be differentially methylated also in the anterior hippocampus, including entorhinal cortex, of non-twin cases and controls. Targeted bisulfite pyrosequencing of the DNA methylation mark in ADARB2 gene in 62 Finnish and Swedish twin pairs revealed that, in addition to the disease status, DNA methylation of this region is influenced by gender, age, zygosity, APOE genotype, and smoking. Further analysis of 120 Swedish twin pairs indicated that this specific DNA methylation mark is not predictive for Alzheimer's disease and becomes differentially methylated after disease onset.ConclusionsDNA methylation differences can be detected in the peripheral blood of twin pairs discordant for Alzheimer's disease. These DNA methylation signatures may have value as disease markers and provide insights into the molecular mechanisms of pathogenesis. We found no evidence that the DNA methylation marks would be associated with gene expression in blood. Further studies are needed to elucidate the potential importance of the associated genes in neuronal functions and to validate the prognostic or diagnostic value of the individual marks or marker panels.

Dataset Information

Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation.

Publications

Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation.

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