Table 4.

Genomic locations of age-related changes in DNA methylation.

Reference	Age	Tissue/cell	Genomic coordinates
Humans*
Day et al. (2013)	30–90	Blood, brain, kidney, muscle	Hypermethylated CpGs are found primarily in CG-islands while hypomethylated sites are very rare in cG-islands in all tissues. For Brain and kidney, the trend was similar for shores. in blood and muscle, the shores were enriched in hypomethylated CpGs.
Raddatz et al. (2013)	18–75	Epidermis	Hypermethylated DMRs are enriched in promoters and hypomethylated DMRs are enriched in enhancers.
Steegenga et al. (2014)	30–43 & 52–66	PBMCs	Hypermethylated DMCGs predominantly present in CC-islands while hypomentylated DMCGs found in less dense CpG regions, e.g., shelves and single CpGs.
Bysani et al. (2017)	28–64	Liver	Enrichment of DMCGs observed at transcription start sites, 5′-untranslated regions, and first exons. Under-representation of DMCGs at the gene body, 3’-UTR, and intergenic regions. Significant enrichment of DMGCs observed at GC-islands and under-represented in shelfs.
Mice*
Sun et al. (2014)	4 & 24	Hematopoietic stem cells	The distribution of CpG sites that are hypo- and hypermethylated with age is similar in CG-islands, shores, and promoters. However, these sites are enriched in the shores and depleted in CG-islands.
Cole et al. (2017)	2 & 22	Liver	DMRs are most abundant in genes, introns, and enhancers and disproportionately enriched at genic super-enhancers in highly expressed genes involved in liver function.
Masser et al. (2017)	3 & 24	Hippocampus	Differential methylation for both CpG and CpH sites is enriched in intergenic and intronic regions and under-represented in promoters, CG islands and specific enhances in both male and female mice.
Hahn et al., 2017	5 & 27	Liver	DMRs are strongly enriched for open chromatin histone marks. Enrichment was more pronounced for hypomethylated DMRs. Hypomethylated DMRs are also strongly enriched for distal and intragenic active enhances and active promoters.
Hadad et al. (2018)	3 & 24	Hippocampus	DMCGs were enriched in introns and shores and under-represented in CG-islands and shelves, exons, and promoters. The depletion of DMCGs is most pronounced in promoters containing CGIs. Enrichment of DMCGs was associated with both repressive and activation histone marks.

^*Age for humans given in years and from mice in months. Abbreviations: PBMC = peripheral blood mononucleated cells; DMR = differentially methylated regions; DMGC = differentially methylated CpG sites. The methylation of these regions or CpG sites change (either increase or decrease) change significantly with increasing age.