DNA Methylation-based Biomarkers And The Epigenetic Clock Theory Of Ageing

[Mito]

Abstract | Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These ‘epigenetic clocks’ link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course. Epigenetic biomarkers may help to address long-standing questions in many fields, including the central question: why do we age?

DNA methylation-based biomarkers and the epigenetic clock theory of ageing | Nature Reviews Genetics

 

[Mito]

There exists hundreds, if not thousands, of studies attempting to correlate DNA methylation with such things as: longevity

Another published last week claiming a breakthrough.

 

[Travis]

Another published last week claiming a breakthrough.

Hmmm. But I can tell you Mito that this article needs to be read carefully because DNA cytosine-5-methylation isn't a post replication methylation event at all, but that the nucleotide itself—five-methylcytosine—is actually synthesized as such. The synthetic pathway of 5-methylcytosine is the same as that for cytosine, the only difference is that β-methylaspartate is used in the former and aspartate in the latter. Thus, the only thing which determines so-called 'DNA methylation' is the β-methylaspartate∶aspartate ratio and cobalamin levels—which is used as a cofactor in enzymes which transform (isomerize) glutamate into β-methylaspartate. Thus, the so-called 'DNAmethylation' very closely approximates the glutamate∶aspartate ratio is those on average diets.

[Diclaimer: There are legitimate forms of DNA methylation such as O-linked and N-linked methylation: Carbon-linked methylation is more energetically demanding and the enzyme purported to do this has kinetic rates identical to nonenzymatic S-adenosylmethionine side reactions, or side-methylations.]​

So this could really correlate with something since the amount of β-methylaspartate would depend on having excessive protein (glutamate) and enough cobalamin to convert it. You would then expect a heavy meat-eater to have highest levels of both of these requirements and vegans the least. Five-methylcytosine could then be a correlate of diet, but on account of the fact that: many vegans supplement cobalamin, vitamin B₁₂ can actually be synthesized by enteral bacteria, and many vegans consume quite a bit of glutamate, I don't think you'd expect to see any Pearson's ratios exceeding the .30 range for this one.

But it certainly makes sense, to me at-least, that 5-methylcytosine would decrease with age simply because protein intake—as glutamate—usually decreases with age.