Genetic mutations that alter DNA methyltransferase activity in developmental disorders, such as Sotos syndrome, produce 5 to 10 year deviations in human epigenetic age.
"There are very exciting findings where people studied certain developmental disorders where where mutations deactivated DNA methyltransferase or mutation rendered it overactive, you know. And sure enough, all of these mutations in humans, you know, affect epigenetic age. And so at that level, we know it has an effect as expected, and the effect is pronounced. It could add fi It could add 5 or 10 years to a person, or or the opposite, you know." (said at 0:42:28)
The speaker accurately describes research showing that mutations in epigenetic machinery genes associated with developmental disorders markedly alter epigenetic age measured by DNA methylation clocks. In a landmark study examining patients with developmental disorders, loss-of-function mutations in NSD1 (which cause Sotos syndrome) were found to substantially accelerate epigenetic aging. However, NSD1 is technically a histone (H3K36) methyltransferase rather than a DNA methyltransferase, although H3K36 methylation directly directs and coordinates downstream DNA methylation patterns.
- context: Screening for genes that accelerate the epigenetic aging clock in humans reveals a role fo… (Genome biology 2019)
"Here, we have examined the human epigenetic clock in patients with a variety of developmental disorders, harboring mutations in proteins of the epigenetic machinery. Using the Horvath epigenetic clock, we perform an unbiased screen for epigenetic age acceleration in the blood of these patients. We demonstrate that loss-of-function mutations in the H3K36 histone methyltransferase NSD1, which cause Sotos syndrome, substantially accelerate epigenetic aging." (abstract, results, passage verified)
pubmedfull study (doi)