The study investigates the epigenetic differences in monozygotic (MZ) twins over their lifetime. Despite sharing a common genotype, MZ twins often exhibit phenotypic differences, which can be attributed to epigenetic variations. The researchers examined DNA methylation and histone acetylation levels in a large cohort of MZ twins, finding that while early in life, twins are epigenetically indistinguishable, older twins show significant differences in DNA methylation and histone acetylation. These differences are more pronounced in twins who have spent less time together, have different lifestyles, and are older. The study also identified specific genomic regions with differential methylation, affecting both repeat DNA sequences and single-copy genes, and these differences are associated with altered gene expression. The findings suggest that epigenetic changes play a crucial role in the phenotypic differences observed in MZ twins and may contribute to the discordant frequency and onset of diseases.The study investigates the epigenetic differences in monozygotic (MZ) twins over their lifetime. Despite sharing a common genotype, MZ twins often exhibit phenotypic differences, which can be attributed to epigenetic variations. The researchers examined DNA methylation and histone acetylation levels in a large cohort of MZ twins, finding that while early in life, twins are epigenetically indistinguishable, older twins show significant differences in DNA methylation and histone acetylation. These differences are more pronounced in twins who have spent less time together, have different lifestyles, and are older. The study also identified specific genomic regions with differential methylation, affecting both repeat DNA sequences and single-copy genes, and these differences are associated with altered gene expression. The findings suggest that epigenetic changes play a crucial role in the phenotypic differences observed in MZ twins and may contribute to the discordant frequency and onset of diseases.