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Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression and cancer.

ABSTRACT: Epigenetic marks are extensively altered in cancer but may also change in normal tissues with age, which is the primary risk factor for most cancers. We conducted an epigenome-wide study to identify age-related methylation sites and examine their relationship to cancer and other underlying epigenetic marks. We analyzed 1006 blood DNA samples of women aged 35-76 years from the Sister Study and found that 7694 (28%) of the 27 578 CpGs assayed were associated with age (false discovery rate, q < 0.05). Using independent data sets, we confirmed 749 'high-confidence' age-related CpG (arCpGs) sites in normal blood. Based on The Cancer Genome Atlas data, we show that these age-related changes are largely concordant in a broad variety of normal tissues and that a significantly higher (71-91%, P < 10(-74)) than expected proportion of increasingly methylated arCpGs (IM-arCpGs) were overmethylated in a wide variety of tumor types. IM-arCpGs sites occurred almost exclusively at CpG islands and were disproportionately marked with the repressive H3K27me3 histone modification (P < 1 × 10(-) (50)). Genes containing these IM-arCpG sites were highly enriched for developmental and signaling pathways (P < 10(-) (10)). Our findings suggest that as cells acquire methylation at age-related sites, they have a lower threshold for malignant transformation that may explain in part the increase in cancer incidence with age.

SUBMITTER: Xu Z

PROVIDER: S-EPMC3908753 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression and cancer.

Xu Zongli Z Taylor Jack A JA

Carcinogenesis 20131128 2

Epigenetic marks are extensively altered in cancer but may also change in normal tissues with age, which is the primary risk factor for most cancers. We conducted an epigenome-wide study to identify age-related methylation sites and examine their relationship to cancer and other underlying epigenetic marks. We analyzed 1006 blood DNA samples of women aged 35-76 years from the Sister Study and found that 7694 (28%) of the 27 578 CpGs assayed were associated with age (false discovery rate, q < 0.0 ...[more]

PMID: 24287154

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Project description:The retrieval (or testing) of information leads to better memory performance compared with reencoding. This phenomenon is known as "testing effect" or "retrieval practice effect" and has been primarily described in behavioral studies with healthy young subjects. However, possible age-related changes and their associated underlying neural processes, in particular neural oscillations, remain unclear. To address this issue, we used a previously established paradigm in healthy young (N = 27) and elderly (N = 28) male and female human adults while their brain activity was being recorded using EEG. Subjects viewed prefamiliarized scene images intermixed with new scenes and classified them as indoor versus outdoor (encoding task) or old versus new (retrieval task). Subsequently, subjects performed a recognition memory task 10 min and 24 h after encoding. Behaviorally, both age groups showed the testing effect at both time points but, importantly, it was less pronounced in the elderly. At the neural level, the retrieval compared with the encoding task was accompanied by power decreases in the alpha (9-12 Hz) and beta bands (13-30 Hz), possibly reflecting task demands, and this difference was more pronounced in the elderly. Finally, a correlation analysis revealed that those elderly who displayed a more pronounced testing effect exhibited a neural pattern that was more similar to the younger subjects. These findings provide evidence that the testing effect decreases across the life span, and they suggest that changes in alpha-beta oscillations play a direct role.SIGNIFICANCE STATEMENT Learning new and retrieving old information is part of everyday human life. Understanding how learning processes can be optimized therefore has direct applications in the realm of educational and rehabilitative contexts. Here, we show that retrieval practice is a strategy to optimize encoding into long-term memory in both young and elderly humans. Importantly, retrieval practice was significantly reduced in the elderly and closely related to changes in alpha (9-13 Hz) and beta band (13-30 Hz) oscillations. Our findings suggest that decreased retrieval practice effects across the life span contribute to, and may reflect, age-related declines in memory performance. They further provide new insights into the underlying neural mechanisms and point toward future avenues for neuro-modulatory interventions.

Dataset Information

Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression and cancer.

Publications

Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression and cancer.

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