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Published on: August 29, 2018
Widespread and tissue specific age-related DNA methylation changes in mice
Shinji Maegawa1, George Hinkal, Hyun Soo Kim
1Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Genome Research
|January 29, 2010
Summary
Aging is associated with widespread DNA methylation changes in mouse intestines, impacting gene expression. This epigenetic deregulation is common in mammals and shows tissue-specific patterns.
Area of Science:
- Epigenetics
- Genomics
- Aging Research
Background:
- Aberrant DNA methylation in promoter CpG islands is linked to cancer and tumor suppressor gene silencing.
- Age-dependent hypermethylation in normal tissues may indicate cancer risk, but its tissue specificity is unknown.
Purpose of the Study:
- To investigate age-related DNA methylation patterns in mouse intestine.
- To determine if age-related methylation is conserved across different tissues and species.
Main Methods:
- Comprehensive DNA methylation profiling of promoter regions in aging C57BL/6 mice (3-mo vs. 35-mo) using methylated CpG island amplification and microarray analysis.
- Quantitative validation of microarray data using pyrosequencing.
- Examination of age-related methylation changes in lung, liver, and spleen tissues.
Main Results:
- Significant age-related hypermethylation (21%) and hypomethylation (13%) were observed in mouse intestinal genes.
- Age-related methylation changes showed tissue specificity, with varying degrees of conservation between mouse and human intestines.
- Polycomb targets in embryonic stem cells were enriched among hypermethylated genes.
Conclusions:
- Epigenetic deregulation, including widespread hyper- and hypomethylation, is a common feature of aging in mammals.
- Age-related DNA methylation exhibits significant tissue specificity.
- Findings suggest a conserved epigenetic component to mammalian aging.
Related Concept Videos
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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