Even though we don’t want to admit it, we all see changes in ourselves as the years pass by. A few more inches round the waistline here, and a little less muscle tone there, all due to a little less exercise and a little more food and drink! But what changes occur in our stem cells as we age and what controls this?
Previous studies covered here at Epigenie have shown that the H3K4me1 histone modification represents a marker of primed enhancers and aids gene expression during embryogenesis. Now, the group of Mario F Fraga has found that H3K4me1 also marks regions of DNA methylation loss during normal ageing in human mesenchymal stem cells (MSCs).
Using the HumanMethylation450 BeadChip platform (See the Epigenie guide to all things related to DNA methylation analysis technology) the group profiled DNA methylation in MSCs obtained from human patients aged from 2 to 92 years, finding that:
- MSCs harbor specific DNA methylation changes in relation to differentiated cell types.
- Only specific genomic loci display common genome wide DNA methylation changes during ageing.
- Repressive histone modifications (H3K9me3 and H3K27me3) mark sequences which gain DNA methylation in MSCs and differentiated cells.
- H3K4me1 marks sequences which lose DNA methylation in MSCs and differentiated cell types, so suggesting that H3K4me1 represents a cell type-independent signature of DNA methylation loss during ageing.
- Inter-individual variability in DNA methylation changes increased during ageing.
- Profiling of genetically identical individuals (monozygotic twins) found that DNA methylation changes depended on both genetic and non-genetic factors.
Further work will hopefully uncover why these specific histone modifications lead to different DNA methylation events with ageing, but the current study does highlight two important points; cell type plays an important role in the regulation of DNA methylation changes over time, and chromatin context is an important cell type-independent mark of DNA methylation.
Can we therefore identify and target stem cell specific alterations during ageing to stop ageing of the tissue as a whole? Or will the repression of genome wide changes be enough to halt father time? Only time will tell, but let’s start by spending some of our precious minutes reading this revealing study in Genome Research, September 2014.