DNA methylation rates scale with maximum lifespan across mammals


DNA methylation rates have previously been found to broadly correlate with maximum lifespan in mammals, yet no precise relationship has been observed. We developed a statistically robust framework to compare methylation rates at conserved age-related sites across mammals. We found that methylation rates negatively scale with maximum lifespan in both blood and skin. The emergence of explicit scaling suggests that methylation rates are, or are linked to, an evolutionary constraint on maximum lifespan acting across diverse mammalian lineages.

I need to spend some time reading this paper to get to properly understand it, but it seems quite interesting.

I have been pondering on why genes get methylated and I am currently thinking that perhaps they get methylated almost at random, but when the gene is transcribed then the methylation is removed. Hence methylation is to some extent a measurement of whether or not a gene is functioning.

The evolutionary advantage of this is to avoid wasting cellular resource on genes that won’t function anyway.


I wonder whether jntra-species variation in methylation genes correlate with longevity. Im thinking mthfr etc

I have just had my attention drawn to this again. I am wondering on a systems basis what causes methylation. Is it something that occurs linked to failed transcription, is it something based upon a logic system or is it something that tends to happen almost at random. I do think a succesful transcription tends to remove methylation, however.

I’ll admit to not understanding this topic at all! I would love to learn more though. I put my 23 and Me raw data into a free methylation analysis and I have quite a few heterozygous and a couple homozygous mutations related to methylation but I have no idea what to do with the information! Hahaha
If anyone knows of a methylation for dummies guide I’d be interested in reading up on it. :slightly_smiling_face:

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Pretty interesting paper.

Also, FYI methylation rate is distinct from methylation. Whereas a given CpG site might be methylated in some percentage of cells within a sample, and this percentage might change with aging in a predictable and statistically significant way (giving rise to age-associated CpGs), the methylation rate measures how rapidly this percentage is changing. Essentially, for a given CpG site, its methylation rate is just the slope when you graph its methylation percentage as a function of time.

So it makes sense that the rate at which the clock ticks increases with decreasing species lifespan.

Similar results found also for the rate of epigenetic drift, which is no longer looking at the median age-associated CpG methylation rate, but looking at age-associated changes in the relation between methylation states of neighboring CpGs.

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It remains that the question of what methylation means functionally is the key.

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