Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context
Brock C. Christensen,E. Andres Houseman,E. Andres Houseman,Carmen J. Marsit,Shichun Zheng,Margaret Wrensch,Joseph L. Wiemels,Heather H. Nelson,Margaret R. Karagas,James F. Padbury,Raphael Bueno,David J. Sugarbaker,Ru Fang Yeh,John K. Wiencke,Karl T. Kelsey +14 more
TLDR
This work provides novel insight into the role of aging and the environment in susceptibility to diseases such as cancer and critically informs the field of epigenomics by providing evidence of epigenetic dysregulation by age-related methylation alterations.Abstract:
Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are related to epigenomic states that vary across individuals. Thus, population-based investigations are needed to further our understanding of the fundamental dynamics of normal individual epigenomes. We analyzed 217 non-pathologic human tissues from 10 anatomic sites at 1,413 autosomal CpG loci associated with 773 genes to investigate tissue-specific differences in DNA methylation and to discern how aging and exposures contribute to normal variation in methylation. Methylation profile classes derived from unsupervised modeling were significantly associated with age (P<0.0001) and were significant predictors of tissue origin (P<0.0001). In solid tissues (n = 119) we found striking, highly significant CpG island-dependent correlations between age and methylation; loci in CpG islands gained methylation with age, loci not in CpG islands lost methylation with age (P<0.001), and this pattern was consistent across tissues and in an analysis of blood-derived DNA. Our data clearly demonstrate age- and exposure-related differences in tissue-specific methylation and significant age-associated methylation patterns which are CpG island context-dependent. This work provides novel insight into the role of aging and the environment in susceptibility to diseases such as cancer and critically informs the field of epigenomics by providing evidence of epigenetic dysregulation by age-related methylation alterations. Collectively we reveal key issues to consider both in the construction of reference and disease-related epigenomes and in the interpretation of potentially pathologically important alterations.read more
Citations
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DNA methylation age of human tissues and cell types
TL;DR: It is proposed that DNA methylation age measures the cumulative effect of an epigenetic maintenance system, and can be used to address a host of questions in developmental biology, cancer and aging research.
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Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates
Gregory Hannum,Justin Guinney,Ling Zhao,Ling Zhao,Li Zhang,Guy Hughes,Srinivas R. Sadda,Brandy Klotzle,Marina Bibikova,Jian-Bing Fan,Yuan Gao,Rob Deconde,Menzies Chen,Indika Rajapakse,Stephen H. Friend,Trey Ideker,Kang Zhang,Kang Zhang +17 more
TL;DR: A quantitative model of aging is built using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101, to measure the rate at which an individual's methylome ages, which is impacted by gender and genetic variants.
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Idiopathic pulmonary fibrosis
TL;DR: In this article, the authors reviewed recent data on the clinical course, therapeutic options, and underlying mechanisms thought to be involved in the pathogenesis of idiopathic pulmonary fibrosis.
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Epigenetics and the environment: emerging patterns and implications.
TL;DR: Although the underlying mechanisms remain largely unknown, particularly in humans, mechanistic insights are emerging from experimental model systems, which have implications for structuring future research and understanding disease and development.
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Principles and challenges of genome-wide DNA methylation analysis
TL;DR: There is such a diversity of DNA methylation profiling techniques that it can be challenging to select one, and this Review discusses the different approaches and their relative merits and introduces considerations for data analysis.
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