Replicative history as a major determinant of epigenetic noise across human tissues

A study analyzing DNA methylation patterns across 14 human tissue types has found that the number of times cells divide, known as mitotic history, plays a crucial role in determining the level of epigenetic noise. This noise, which measures the loss of precise epigenetic information, was consistently lower in regions like promoter areas, first exons, and CpG islands, while higher in CpG-poor and intergenic regions.

The research, which analyzed genome-wide DNA methylation profiles from 1,531 healthy human samples, revealed that cumulative mitotic history had a stronger association with epigenetic noise than chronological age. This effect was particularly pronounced in CpG-rich regulatory regions. In contrast, age-related, replication-independent factors seemed to dominate in low-proliferative tissues such as the brain.

The study also found that biological age acceleration was largely due to cell division, but this effect varied across different tissues. In summary, mitotic history emerged as a major determinant of epigenetic noise accumulation across human tissues, while the biological context influenced the vulnerability of specific regions to methylation information loss during the aging process.