GrimAge: methlyation DNA change, mortality

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Discussion Overview

The discussion revolves around the concept of DNA methylation as a biomarker for predicting mortality and healthspan, particularly focusing on the GrimAge model. Participants explore the mechanisms of DNA methylation, its implications for aging, and the accuracy of predictions derived from such analyses.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • Some participants describe DNA methylation as a universal "calendar" that records age-related changes, suggesting that it can provide insights into an individual's risk of mortality.
  • One participant questions the accuracy of the GrimAge model, specifically the claim that it is 18% more accurate than calendar age, and seeks clarification on the implications of this statistic.
  • Another participant speculates that the popular article may be based on an interview, indicating uncertainty about the source of the claims made.
  • There is a discussion about the role of methylation in gene expression, with one participant arguing that it is not a direct measure of DNA damage but rather a long-term regulatory mechanism that may reflect developmental processes and the accumulation of senescent cells.
  • Concerns are raised about the predictive accuracy of the GrimAge test and the need for further confirmation before it becomes widely accepted.

Areas of Agreement / Disagreement

Participants express differing views on the interpretation of DNA methylation and its implications for mortality prediction. There is no consensus on the accuracy or applicability of the GrimAge model, and the discussion remains unresolved regarding its reliability and the mechanisms involved.

Contextual Notes

Some assumptions about the relationship between DNA methylation and aging processes are not fully explored. The discussion also highlights the need for clarity regarding statistical claims and the mechanisms underlying the observed phenomena.

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TL;DR
DNA methylation - Grimage strongly predicts lifespan and healthspan
Popular precis:
https://www.aging-us.com/dna-methylation-grimage-strongly-predicts-lifespan-and-healthspan Ake Lu, Steve Horvath
David Geffen School of Medicine at UCLA

DNA biomarkers measure an individual’s risk of mortality by analyzing positions on the DNA where methyl groups change with age. These positions are analysed by applying DNA from blood onto a “chip”, which measures the degree of their methylation.

My take:
While DNA may change anywhere due to methylation, so that cells in a given tissue may have different damage points on DNA, there apparently is a Universal "calendar" (or clock if you like) that is consistent for recording methylation changes. Sampling methylation states using ~1000 places on sample DNA from the parts of this calendar is the first step. Next step is applying metrics using GrimAge software on the sample data to give an overall estimate of age-related DNA damage. The changes to DNA start in utero. And persist throughout life.

One result is in units called packyears - number of years of smoking.

Aging appears to be an open source journal. @Ygggdrasil likely knows more details about this universal calendar. I'm strictly an outsider.
 
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18% more accurate than calendar age. Does that mean if mortality tables predict 20+-10 years they can predict with an uncertainty of 10/1.18=8.5 years? The original study doesn't have "18" anywhere with such a meaning.
 
The popular article is based on an interview. It could an explanatory example from that interview...? Merely a guess.
 
Methylation is one of the many methods used to control gene expression, in this case it stops gene expression and it is a long term action. Its not a measure of DNA damage which clearly does accumulate with age. I suspect there are a great many processes in our body that are turned on at particular times in our lives and then turned off, its a characteristic of our development. So it would make sense that as we age we would see more evidence of gene expression being disabled, we also accumulate in our tissues an increasing number of senescent cells, cells that are alive but essentially none functioning. My own view is that it is these things that this test might be measuring, really we have little information about specific blood proteins that are reliable indicators of future health, if we did this is what we would be measuring.
I can't see the predictive accuracy will have people clamouring for this test to be available and I think it requires some confirmation.
 

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