(CpG) is the least frequent dinucleotide, making up less than 1% of all dinucleotides (see CG suppression). At most CpG sites cytosine is methylated to form 5-methylcytosine. As indicated in the article CpG site, in mammals, 70% to 80% of CpG cytosines are methylated. However, in vertebrates there are CpG islands, about 300 to 3,000 base pairs long, with interspersed DNA sequences that deviate significantly from the average genomic pattern by being CpG-rich. These CpG islands are predominantly nonmethylated. In humans, about 70% of promoters located near the transcription start site of a gene (proximal promoters) contain a CpG island (see CpG islands in promoters). If the initially nonmethylated CpG sites in a CpG island become largely methylated, this causes stable silencing of the associated gene. For humans, after adulthood is reached and during subsequent aging, the majority of CpG sequences slowly lose methylation (called epigenetic drift). However, the CpG islands that control promoters tend to gain methylation with age. The gain of methylation at CpG islands in promoter regions is correlated with age, and has been used to create an epigenetic clock (see article Epigenetic clock). There may be some relationship between the epigenetic clock and epigenetic alterations accumulating after DNA repair. Both unrepaired DNA damage accumulated with age and accumulated methylation of CpG islands would silence genes in which they occur, interfere with protein expression, and contribute to the aging phenotype. See also Aging brain Biological immortality DNA damage (naturally occurring) DNA repair Life expectancy Longevity Maximum life span Rejuvenation Senescence Telomere References DNA Programmed cell death Proximate theories of biological ageing Senescence Theories of biological ageing Theories of ageing