5 ms·

Epigenetic age oscillates during the day

85 points by kkoncevicius 2y ago

Terr_ 2y ago
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 2y ago
  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 https://www.nature.com/articles/s41467-023-42588-6
- gwern 2y ago
  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...
  - deleted 2y ago
    [deleted]
  - biomcgary 2y ago
    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 2y ago
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 2y ago
  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 2y ago
  > 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.
- lowestprimate 2y ago
  How are you taking your temperature? Infrared sensor on the forehead? Infrared only measures surface temperatures and can give false readings of temperature based on how the body "radiator" system is working.
  - huytersd 2y ago
    Under the tongue.
  - TeMPOraL 2y ago
    The fluctuations aren't that bad. Now, I don't trust the infrared sensors myself, because I can't see the "local gradient" of what they're measuring, nor how it changes momentarily (why does it always take a second or two to measure?), and there certainly are areas on the face that vary by whole degree centigrade in temperature. How do I know? Because I got so annoyed at the IR thermometers that I recently got myself one of those USB-C thermal cameras (UTi721M, specifically). It's like a 256x192 array of IR thermometers, measuring continuously, so you actually see what's going on. Lots of interesting things you can learn that way, for example that cheeks, chin and nose can easily be 1-2℃ cooler than the forehead, or that the neck/throat shows about the same temperature that the forehead, but seems more stable. And, it's much faster to take temp of everyone at home in one go. And then you also can learn a lot about your own environment, too. I highly recommend this to anyone. That said, I found in-ear IR most reliable, and use it as a baseline for health checkups. You do however need to watch out for insertion - if you put the head in the ear too fast and measure immediately, you can get a result that's a degree or two centigrade above correct, which I imagine is because of momentary friction heating.
biomcgary 2y ago
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 2y ago
  What's your company? I'd be interested in learning more about (multi-omics, etc.)
  - biomcgary 2y ago
    We're still in lite stealth mode, so posting the name on HN isn't the best idea. :-)
    - greenish_shores 2y ago
      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 2y ago
        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 2y ago
Haha it's really a marketing tool for bespoke medicine. Not really that useful in that field but people like it.
- JumpCrisscross 2y ago
  > 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 2y ago
    If they think so, and I don't, then we just disagree on this and history will see who is right.
    - JumpCrisscross 2y ago
      > 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/ https://pubmed.ncbi.nlm.nih.gov/34415665/
      - renewiltord 2y ago
        All right. Use it as a health target for yourself. It's no skin off my back.
  - nradov 2y ago
    Here's one source. https://doi.org/10.1016/j.cell.2022.11.001 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.
claytongulick 2y ago
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 2y ago
  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 2y ago
    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 2y ago
      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.
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?”

85 points by kkoncevicius 2y ago

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 2y ago
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 https://www.nature.com/articles/s41467-023-42588-6
gwern 2y ago
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...
- deleted 2y ago
  [deleted]
- biomcgary 2y ago
  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 2y ago

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 2y ago
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 2y ago
> 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.
lowestprimate 2y ago
How are you taking your temperature? Infrared sensor on the forehead? Infrared only measures surface temperatures and can give false readings of temperature based on how the body "radiator" system is working.
- huytersd 2y ago
  Under the tongue.
- TeMPOraL 2y ago
  The fluctuations aren't that bad. Now, I don't trust the infrared sensors myself, because I can't see the "local gradient" of what they're measuring, nor how it changes momentarily (why does it always take a second or two to measure?), and there certainly are areas on the face that vary by whole degree centigrade in temperature. How do I know? Because I got so annoyed at the IR thermometers that I recently got myself one of those USB-C thermal cameras (UTi721M, specifically). It's like a 256x192 array of IR thermometers, measuring continuously, so you actually see what's going on. Lots of interesting things you can learn that way, for example that cheeks, chin and nose can easily be 1-2℃ cooler than the forehead, or that the neck/throat shows about the same temperature that the forehead, but seems more stable. And, it's much faster to take temp of everyone at home in one go. And then you also can learn a lot about your own environment, too. I highly recommend this to anyone. That said, I found in-ear IR most reliable, and use it as a baseline for health checkups. You do however need to watch out for insertion - if you put the head in the ear too fast and measure immediately, you can get a result that's a degree or two centigrade above correct, which I imagine is because of momentary friction heating.

biomcgary 2y ago

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 2y ago
What's your company? I'd be interested in learning more about (multi-omics, etc.)
- biomcgary 2y ago
  We're still in lite stealth mode, so posting the name on HN isn't the best idea. :-)
  - greenish_shores 2y ago
    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 2y ago
      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 2y ago

Haha it's really a marketing tool for bespoke medicine. Not really that useful in that field but people like it.

JumpCrisscross 2y ago
> 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 2y ago
  If they think so, and I don't, then we just disagree on this and history will see who is right.
  - JumpCrisscross 2y ago
    > 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/ https://pubmed.ncbi.nlm.nih.gov/34415665/
    - renewiltord 2y ago
      All right. Use it as a health target for yourself. It's no skin off my back.
- nradov 2y ago
  Here's one source. https://doi.org/10.1016/j.cell.2022.11.001 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.

claytongulick 2y ago

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 2y ago
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 2y ago
  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 2y ago
    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.

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?”