Amazing stuff! This could be a breakthrough!
"... describe a never-before-seen link between the two most accepted explanations: random genetic mutations and predictable epigenetic modifications. The latter, also known as the epigenetic clock theory, has been widely used by scientists as a consistent, quantitative measure of biological aging. ...
"Major research institutions and companies are betting on turning back the epigenetic clock as a strategy to reverse the effects of aging, but our research suggests that this may only be treating a symptom of aging, not the underlying cause,” ...
There are two prevailing theories about the relationship between aging and DNA. The somatic mutation theory suggests that aging is caused by the accumulation of mutations, permanent changes in our DNA sequence that occur randomly.
The epigenetic clock theory suggests that aging occurs due to the accumulation of epigenetic modifications, minor changes to the chemical structure of DNA that do not alter the underlying sequence, but instead change which genes are on or off. Unlike mutations, epigenetic modifications can also be reversed in some cases. ...
To answer this fundamental question, researchers analyzed data from 9,331 patients catalogued in the Cancer Genome Atlas and the Pan-Cancer Analysis of Whole Genomes. By comparing genetic mutations to epigenetic modifications, they found that mutations were predictably correlated with changes in DNA methylation, one type of epigenetic modification. They found that a single mutation could cause a cascade of epigenetic changes across the genome, not just where the mutation occurred. Using this relationship, the researchers were able to make similar predictions of age using either mutations or epigenetic changes. ...
“Our study demonstrates for the first time that epigenetic changes are intricately and predictably tied to random genetic mutations.” ..."
From the abstract:
"DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates.
In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but with pervasive remodeling of the methylome out to ±10 kilobases.
This one-to-many mapping allows mutation-based predictions of age that agree with epigenetic clocks, including which individuals are aging more rapidly or slowly than expected. Moreover, genomic loci where mutations accumulate with age also tend to have methylation patterns that are especially predictive of age. These results suggest a close coupling between the accumulation of sporadic somatic mutations and the widespread changes in methylation observed over the course of life."
Why Our Biological Clock Ticks: Research Reconciles Major Theories of Aging (original news release) "Two prominent explanations for aging are not so different after all; results call current anti-aging strategies into question"
Somatic mutation as an explanation for epigenetic aging (no public access)
Somatic mutation as an explanation for epigenetic aging (prepring, open access)
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