I have blogged an article looking superficially at the interplay between gene transcription and methylation.
HannumAge is just strange, I’ve seen people with extreme negative deviations in their HannumAge (uniquely) - even those with accelerated HorvathAge, and I don’t think it means anything. It seems weirdly strongly sensitive to a lot of things.
It’s mostly noise, I expect that within a few years, we’ll be discounting it way more b/c more modern clocks will be used more often.
To me, however, it is the broader question of the interplay between gene expression (particularly transcription) and methylation that is interesting.
It appears quite clear that you can reduce methylation by ensuring that DNA is transcribed. I read that both from my own data where all of the methylation clocks show a reduction in methylation. The real problem with the clocks is that they only look at lymphocytes from blood samples and we are guessing about the rest.
This does fit with the aging of cells being a bit sticky and demonstrates that the use of my protocol gradually reduces methylation.
It would actually be useful to have a more direct measure of the proportion of CpG sites that are methlyated.
This also fits with “use it or lose it” as a biological principle.