3 ms·

I mean epigenetic clocks are extremely unreliable and have enormous error bars. It is not surprising that they are easily influenced by additional variables.

by V__ 2y ago

kkoncevicius 2y ago
Epigenetic clocks are one of the (if not the) most accurate ways to estimate someone's real chronological age using molecular level data. So not sure what you mean by "extremely unreliable".
- epistasis 2y ago
  I disagree, because "real age" is defined in terms of the epigenetic clock. We don't have enough time observing them with humans to connect them to real age, at least as far as I have ever seen. If there's some major paper I have missed, and my other sources have missed, I'd love to see it.
  - deleted 2y ago
    [deleted]
  - pc86 2y ago
    Real age is chronological age, full stop. If you were born 50 years ago today, you're 50 years old. Age is a concrete, mathematical thing. That your cells appear to be younger or older to your actual (chronological) age is irrelevant. You don't get to say your "real age" is 45 because your cells are slightly better than they "should be."
    - voisin 2y ago
      I think you two are talking past each other. “I am 50 years old” is a statement of fact like you refer. “Real age” is essentially a term of art used to describe your relative health - a single number to indicate the cumulative impact of your lifestyle, genes, etc. No one says “I have a real age of 50” to the question “how old are you?”
      - epistasis 2y ago
        Thanks. Moreover nobody would use an epigenetic clock to refer to chronological age, because it's inferior in every way for that purpose. The purported use of an epigenetic clock in humans is that it predicts either aging effects of remaining life span in some sense; neither of these have been proven to be biologically true because in the first we don't necessarily have the definition of aging, and certainly don't have it down to a single axis, at best it is understood along many different dimensions, many of which are not captured by epigenetic measures. And second sense, predicting remaining life span, is completely unproven. Even more speculative is whether measures which change a person's epigenetic age will result in changes in remaining lifespan. There's a chance that epigenetic age becomes useful for something, but it's just a chance. It's not established science.
- deleted 2y ago
  [deleted]
- V__ 2y ago
  They probably are the most accurate way, but that still doesn't make them good. If there haven't been any recent breakthroughs I missed, then we are talking about getting it right +/- 4 years under ideal conditions. Repeating these test on the same subjects can result in fluctuations of 8 to 12 years [1]. Additionally, there are a lot of biotech/junk studies claiming some new intervention reduces/reverses biologic age using these epigenetic clocks as evidence. Making me very wary of the whole thing, though unfairly to those actually doing sound studies I admit. [1] https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-022-01293-9 https://clinicalepigeneticsjournal.biomedcentral.com/article...
  - kkoncevicius 2y ago
    I think we mostly agree. If you are interested, there are developments that reduce the fluctuations of clock predictions - like principal component based clocks [1], where the authors claim average difference between replicate measurements of 1.5 years. And the study you are citing (8 to 12 year errors) - seems to report maximum errors, not averages. These might be caused by poor quality samples, so it's unfair to report it like that. Also the publication under discussion (epigenetic age oscillates) would answer where the fluctuations observed by the article you linked to come from - part of them are of course technical due to measurement error, but part of them are influenced by differences in sample collection times. I also share your skepticism about intervention research and using "biological clocks" to measure how healthy you are. Curiously chronological clocks seem to not be easily affected by interventions. And I would guess this is why most people doing epigenetic aging for sport use biological clocks (like DunedinPACE). But then the question - if you are younger according to "biological age", but we still can measure your true chronological age accurately - are you actually younger in a meaningful sense. [1]: https://www.nature.com/articles/s43587-022-00248-2 https://www.nature.com/articles/s43587-022-00248-2
    - V__ 2y ago
      Thanks for the link, that would be a great improvment. I really hope they get their someday.

I mean epigenetic clocks are extremely unreliable and have enormous error bars. It is not surprising that they are easily influenced by additional variables.

by V__ 2y ago

I mean epigenetic clocks are extremely unreliable and have enormous error bars. It is not surprising that they are easily influenced by additional variables.

kkoncevicius 2y ago

Epigenetic clocks are one of the (if not the) most accurate ways to estimate someone's real chronological age using molecular level data. So not sure what you mean by "extremely unreliable".

epistasis 2y ago
I disagree, because "real age" is defined in terms of the epigenetic clock. We don't have enough time observing them with humans to connect them to real age, at least as far as I have ever seen. If there's some major paper I have missed, and my other sources have missed, I'd love to see it.
- deleted 2y ago
  [deleted]
- pc86 2y ago
  Real age is chronological age, full stop. If you were born 50 years ago today, you're 50 years old. Age is a concrete, mathematical thing. That your cells appear to be younger or older to your actual (chronological) age is irrelevant. You don't get to say your "real age" is 45 because your cells are slightly better than they "should be."
  - voisin 2y ago
    I think you two are talking past each other. “I am 50 years old” is a statement of fact like you refer. “Real age” is essentially a term of art used to describe your relative health - a single number to indicate the cumulative impact of your lifestyle, genes, etc. No one says “I have a real age of 50” to the question “how old are you?”
    - epistasis 2y ago
      Thanks. Moreover nobody would use an epigenetic clock to refer to chronological age, because it's inferior in every way for that purpose. The purported use of an epigenetic clock in humans is that it predicts either aging effects of remaining life span in some sense; neither of these have been proven to be biologically true because in the first we don't necessarily have the definition of aging, and certainly don't have it down to a single axis, at best it is understood along many different dimensions, many of which are not captured by epigenetic measures. And second sense, predicting remaining life span, is completely unproven. Even more speculative is whether measures which change a person's epigenetic age will result in changes in remaining lifespan. There's a chance that epigenetic age becomes useful for something, but it's just a chance. It's not established science.
deleted 2y ago
[deleted]
V__ 2y ago
They probably are the most accurate way, but that still doesn't make them good. If there haven't been any recent breakthroughs I missed, then we are talking about getting it right +/- 4 years under ideal conditions. Repeating these test on the same subjects can result in fluctuations of 8 to 12 years [1]. Additionally, there are a lot of biotech/junk studies claiming some new intervention reduces/reverses biologic age using these epigenetic clocks as evidence. Making me very wary of the whole thing, though unfairly to those actually doing sound studies I admit. [1] https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-022-01293-9 https://clinicalepigeneticsjournal.biomedcentral.com/article...
- kkoncevicius 2y ago
  I think we mostly agree. If you are interested, there are developments that reduce the fluctuations of clock predictions - like principal component based clocks [1], where the authors claim average difference between replicate measurements of 1.5 years. And the study you are citing (8 to 12 year errors) - seems to report maximum errors, not averages. These might be caused by poor quality samples, so it's unfair to report it like that. Also the publication under discussion (epigenetic age oscillates) would answer where the fluctuations observed by the article you linked to come from - part of them are of course technical due to measurement error, but part of them are influenced by differences in sample collection times. I also share your skepticism about intervention research and using "biological clocks" to measure how healthy you are. Curiously chronological clocks seem to not be easily affected by interventions. And I would guess this is why most people doing epigenetic aging for sport use biological clocks (like DunedinPACE). But then the question - if you are younger according to "biological age", but we still can measure your true chronological age accurately - are you actually younger in a meaningful sense. [1]: https://www.nature.com/articles/s43587-022-00248-2 https://www.nature.com/articles/s43587-022-00248-2
  - V__ 2y ago
    Thanks for the link, that would be a great improvment. I really hope they get their someday.