[HN Gopher] Epigenetic age oscillates during the day
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Epigenetic age oscillates during the day
Author : kkoncevicius
Score : 74 points
Date : 2024-04-19 16:48 UTC (6 hours ago)
(HTM) web link (onlinelibrary.wiley.com)
(TXT) w3m dump (onlinelibrary.wiley.com)
| Terr_ wrote:
| That certainly breathes new life into old metaphors like
| "twilight years".
|
| It sounds like the most immediate takeaway is that anyone
| analyzing this stuff needs to control for _when_ measure
| individuals.
| kkoncevicius wrote:
| And not just this stuff but a lot of health metrics probably
| have this occult dependence on the time of day. For example
| MRIs [1].
|
| [1]: https://www.nature.com/articles/s41467-023-42588-6
| gwern wrote:
| The potential for systematic bias here is also quite
| concerning. Imagine your experimental group tends to come in
| the morning (maybe because they're on-site) but your control
| group is scheduled to come in the rest of the day...
| biomcgary wrote:
| This problem is VERY real and happens in surprising ways. My
| biotech has a dataset that was collected over several years
| and we found this pattern of older people having more Vitamin
| D in their blood than younger people, which is the opposite
| of the published literature. It turns out that the sample
| collection was initially year round but switched to summer
| only and everyone in the cohort was older, by definition, in
| the later collection.
| huytersd wrote:
| Even things like posture seem to affect my parameters. My temp
| will be 98.4 while seated but if I stand up and check it, it
| drops down to 97.9.
| jajko wrote:
| Maybe its just not a good enough measure for any form of age?
| Some folks get obsessed with numbers without seeing bigger
| picture and focusing on actually important things in life (just
| general observation, please don't take any of this personally)
| Aurornis wrote:
| > My temp will be 98.4 while seated but if I stand up and check
| it, it drops down to 97.9
|
| Body temperature measurements from outside the body are
| impacted by changes in blood flow, which will happen when you
| stand up.
|
| Your core body temperature isn't fluctuating, the temperature
| at the measurement point is changing slightly because you've
| changed your blood flow.
|
| We're constantly losing heat from our bodies to the
| environment. You could probably get similar measurements if you
| heavily insulated the entire area around the thermometer and
| let measurements stabilized.
|
| In other words: Don't read too much into this experiment.
| biomcgary wrote:
| I work at a biotech that does intersecting research (predicting
| disease risk). We obsess about temporal variation at various time
| scales and the effects are quite real. We use multiple data
| planes (multi-omics) to evaluate temporal effects across diverse
| biology. Our goal is to ensure that our long-term predictions are
| minimally impacted by short-term fluctuations.
| canadiantim wrote:
| What's your company? I'd be interested in learning more about
| (multi-omics, etc.)
| biomcgary wrote:
| We're still in lite stealth mode, so posting the name on HN
| isn't the best idea. :-)
| greenish_shores wrote:
| I think I can relate to this, even despite mine is just
| purely software startup (but it's low-level
| software/firmware for off-the-shelf devices, which can only
| run commercial closed ones at the moment). Too much
| attention before our product is mature enough would be
| easily able to kill that. We won't be able to handle
| whatever could arise from that with our several-person
| team.
|
| But that's me. Mind sharing your reasons? Of course could
| be obscured as much as you need.
| biomcgary wrote:
| In this context, stealth helps with trust and
| communication. Although that might seem paradoxical, we
| are initially working with a small number of members
| reached by word of mouth.
|
| We walk members through our data usage policies in person
| and ask questions to ensure we understand both their
| health and privacy concerns. Without long-term
| trustworthiness on our part, we won't get the
| longitudinal data that we need to ensure that we continue
| building the best in class predictive models.
|
| There are other reasons, but that's the biggest one.
| renewiltord wrote:
| Haha it's really a marketing tool for bespoke medicine. Not
| really that useful in that field but people like it.
| JumpCrisscross wrote:
| > _Not really that useful in that field_
|
| Source? Because I know people working on it as a target measure
| at a national lab in India as well as at Pfizer (in America)
| and Novartis (in Switzerland).
| renewiltord wrote:
| If they think so, and I don't, then we just disagree on this
| and history will see who is right.
| JumpCrisscross wrote:
| > _then we just disagree on this and history will see who
| is right_
|
| That's not how science works.
|
| Epigenetic age prediction is an area of active research for
| general diagnostic and treatment vectors [1]. There are
| peer-reviewed studies on the stuff. You claimed "really a
| marketing tool for bespoke medicine". That appears to be
| false.
|
| [1] https://pubmed.ncbi.nlm.nih.gov/34415665/
| renewiltord wrote:
| All right. Use it as a health target for yourself. It's
| no skin off my back.
| nradov wrote:
| Here's one source.
|
| https://doi.org/10.1016/j.cell.2022.11.001
|
| Epigenetic alterations such as DNA methylation are only one
| hallmark of aging, and not the most useful one in most cases.
| Interventions to reduce those epigenetic alternations have
| generally not proven effective in extending lifespans or
| improving health outcomes.
| JumpCrisscross wrote:
| > _Epigenetic alterations such as DNA methylation are only
| one hallmark of aging, and not the most useful one in most
| cases. Interventions to reduce those epigenetic
| alternations have generally not proven effective in
| extending lifespans or improving health outcomes_
|
| Thank you. And I totally agree. It reminds me of telomere
| craze in the early noughties.
|
| It not being a panacea, however, is different from it being
| useless. Marking it as pure marketing makes it sound like
| it's cosmetics. It's not. The first research on
| chronological age prediction dates from 2011; we're still
| in the basic research phase. (Which the article mentioned
| is. It's not marketing any treatment.) To the degree it's
| being turned into a scam it's in supplements, not bespoke
| medicine.
| dahinds wrote:
| That doesn't really contradict the post you're responding to,
| does it? (they say it is not that useful for bespoke
| medicine, you say that people are using it for research
| purposes, both can be true?)
| claytongulick wrote:
| One of the "dirty secrets" in healthcare is similar issues with
| BP.
|
| Things like posture, white-coat syndrome, having to pee, cuff
| placement, cuff size, arm position, muscularity, arm diameter,
| time sitting, and many other variables have a massive influence
| on blood pressure.
|
| BP is kind of like weight - it should be taken at regular
| intervals during the day, at the same times, and averaged out
| over time to look at trends. "Snapshot" BP readings are most
| useful for things like hypertensive crisis, not ongoing BP
| management.
|
| Unfortunately, we see a lot of people put on BP meds where other
| interventions may be more appropriate based on bad BP
| measurements.
|
| I think there are a lot of things in healthcare like this, where
| our models are too simplistic and result in flawed understanding
| and consequently ineffective treatments.
| hzay wrote:
| Is it really secret though? It's the first thing you learn when
| you google "how to take bp". Like I'm not a medical person but
| when I was pregnant, I was asked to check BP and I asked the
| doctor "should I like average 3 readings or something?" and she
| said "just take one, don't stress it".
|
| This is well known re thyroid medication as well. Also re
| weight, progesterone, a bunch of things.
| pc86 wrote:
| It's not a secret. Most of my immediate family is or was in
| healthcare and nobody is getting put on BP meds because of a
| single errant reading. They're getting put on meds because of
| persistent, uncontrolled elevated BPs and with non-
| pharmaceutical interventions not addressing it. Everyone,
| especially physicians, know there's a list of 20-30 things
| that can give you temporarily elevated BP that won't respond
| to BP meds.
| importantbrian wrote:
| Yeah, that's been my experience. Everytime I see my primary
| my BP is elevated in the office and they send me home with
| a log and I have to take my BP multiple times a day for 2
| weeks and at home it's fine, so I've never been put on meds
| for it even though it's very high in the office.
| devmor wrote:
| I realized this a couple years ago when I moved and started
| getting my blood tests done at a new lab that was nearby.
|
| My entire life I've had perfect blood pressure, but suddenly
| this lab thinks I have hypertension. After 3-4 visits and
| checking my own BP during the day, I realized that my blood
| pressure is just higher in the morning - I never set
| appointments in the morning previously because I lived too far
| from a lab to make morning appointments convenient.
| greenish_shores wrote:
| What makes them think you have hypertension with purely blood
| laboratory tests? Electrolyte levels ratios? They aren't
| changed in all types of hypertension (won't be changed in
| most, probably), but that's just my wild guess.
| nradov wrote:
| Yes, blood pressure measurement is a real mess. Besides the
| factors you listed, I have found that temperature has a
| surprisingly large impact. If your hands are cold, then that
| causes peripheral vasoconstriction and raises BP.
| voisin wrote:
| Question, since you seem to know a lot about this: is high
| blood pressure meant to be a description of a persistent
| condition (I.e. took a reading at 5, 10, 20 minute intervals at
| rest and stayed elevated) or is it meant to be a description of
| something else (after standing up, or after walking, etc etc)?
| importantbrian wrote:
| I have really bad white-coat hypertension. Like 150-90 in the
| drs. office. So every time I go in they send me home with a
| chart and I have to dutifully record my blood pressure a couple
| of times a day for 2 weeks and send it back to them, and when
| measured at home it's totally fine.
|
| Since I have the cuff I check it every so often to make sure
| it's still fine and it is, but the moment I get in a drs.
| office boom it spikes. This is even true when I'm there for
| someone else like my son or my wife. I can feel that my blood
| pressure is high.
|
| I have absolutely no explanation for why except that I had a
| major surgery when I was 5 and there must be some suppressed
| trauma from that that comes out physically when I'm in a
| doctor's office.
| greenish_shores wrote:
| "Cuffless" blood pressure measurements, which could be easily
| used to measure BP continuously, could easily solve this
| problem.[0][1]
|
| [0]
| https://www.frontiersin.org/articles/10.3389/fcvm.2019.00040...
|
| [1] https://www.cnet.com/health/medical/i-have-high-hopes-for-
| th...
| V__ wrote:
| 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 wrote:
| 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 wrote:
| 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.
| pc86 wrote:
| 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 wrote:
| 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 wrote:
| 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.
| V__ wrote:
| 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/arti
| cle...
| kkoncevicius wrote:
| 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
| V__ wrote:
| Thanks for the link, that would be a great improvment. I
| really hope they get their someday.
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