Scary DNAge result

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vegarejuvinated
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Scary DNAge result

Postby vegarejuvinated » Sun Sep 19, 2021 3:59 pm

Hi All - I recently ran a DNAge test to check on how my interventions were going. I’ve read that these tests based on Horvaths clock are pretty accurate and I was keen to get a sense (and honestly felt like it would make me feel good as I’m fitter than most people I know which a good body weight and healthy habits). Imagine my surprise when my bio age came back as 69 when my chrono age is 47! I have emailed DNAge but they don’t seem interested in communicating with me :x

I did the blood test not urine and I think this is maybe a reflection on my immune system (long standing challenges with allergies and autoimmune conditions)

Thanks in advance to anyone who can help me troubleshot this disturbing result.

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floramaria
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Re: Scary DNAge result

Postby floramaria » Mon Sep 20, 2021 11:14 pm

vegarejuvinated wrote:Hi All - I recently ran a DNAge test to check on how my interventions were going. I’ve read that these tests based on Horvaths clock are pretty accurate and I was keen to get a sense (and honestly felt like it would make me feel good as I’m fitter than most people I know which a good body weight and healthy habits). Imagine my surprise when my bio age came back as 69 when my chrono age is 47! I have emailed DNAge but they don’t seem interested in communicating with me :x

I did the blood test not urine and I think this is maybe a reflection on my immune system (long standing challenges with allergies and autoimmune conditions)

Thanks in advance to anyone who can help me troubleshot this disturbing result.
I wish I had some insights to offer, but unfortunately I don’t. It does seem strange though that as someone who is generally fit you’d get those results. Maybe you are right about the allergies and autoimmune conditions. Please post an update if you learn anything more about this.
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NF52
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Re: Scary DNAge result

Postby NF52 » Tue Sep 21, 2021 11:54 am

vegarejuvinated wrote:... I’m fitter than most people I know which a good body weight and healthy habits). Imagine my surprise when my bio age came back as 69 when my chrono age is 47! ...
Thanks in advance to anyone who can help me troubleshot this disturbing result.
Hello to an Aussie 4/4 from someone who is also ApoE 4/4 and at the chronological age of 69!

My first, deeply held belief is this: All numbers are only estimates of greatly limited samples with predictions for large populations, not for individuals. I was not quite 62 when I learned my 4/4 results, and the first link on 23&me announced: "Average age of diagnosis of Alzheimer's dementia is 68." Yikes! It was only after thinking about WHO got taken to a research center for diagnosis of dementia and also tested for ApoE status in the years before 2014 that I realized they were people 1) unexpectedly young with memory issues and 2) people whose loved ones desperately wanted an answer.

I decided to not sweat the predictions and instead seek to leverage lots of good information and my own knowledge of what seems to work. (And to volunteer for some clinical trials of healthy ApoE 4's.) So here's an April 2021 article that's been picked up by the U.S. National Institute of Health for free access:
Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers One of the co-authors is Dr. Richard Isaacson, the Director of the Alzheimer's Prevention Program at Cornell Weill Medical Center in NYC. The recommendations and the acknowledgements that the science is evolving led me to read it carefully.

Dr. Isaacson was also the lead author on a 2018 article you might also like: Clinical Application of APOE in Alzheimer’s Prevention: A Precision Medicine Approach Here's his top recommendation from the article:

Physical activity
A systematic review of 16 prospective studies concluded that physical activity decreased the risk of developing AD by 45%
...The findings also suggest that physical activity may prevent Aβ accumulation that occurs in the brains of ε4 carriers before clinical symptoms of AD even become apparent
As an aside, a quick look at an earlier post of your about PPRA (G/G) as a metabolic risk gene seems to be different than articles showing it is seen in elite endurance athletes. So maybe you ARE incredibly fit and the methylation DNA test is measuring one, but not a telling, biomarker.

You may also want to browse/read the WIKI on Methylation by our expert SusanJ, and to think about asking your FM doctor for a B12 test.

Trust in your body's ability to read itself!! And plan to report back in 22 years that you're doing great!
4/4 and still an optimist!

vegarejuvinated
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Re: Scary DNAge result

Postby vegarejuvinated » Tue Sep 21, 2021 2:54 pm

floramaria wrote: Iwish I had some insights to offer, but unfortunately I don’t. It does seem strange though that as someone who is generally fit you’d get those results. Maybe you are right about the allergies and autoimmune conditions. Please post an update if you learn anything more about this.


Hi Floramaria - thanks for your response and moral support. :D I’ll let you know anything I find out as I dig deeper.
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vegarejuvinated
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Re: Scary DNAge result

Postby vegarejuvinated » Tue Sep 21, 2021 2:59 pm

NF52 wrote:Hello to an Aussie 4/4 from someone who is also ApoE 4/4 and at the chronological age of 69!


Hi NF52 - thanks for your helpful links. I have a copy of the nutrition report to read through and have scanned the methylation wiki which is very comprehensive. I’m going to get a full set of blood tests - the most recent ones showed very high B vitamin status and low Zinc (I’ve been doing IV vitamins which might explain the high b’s and lots of sauna which might explain the low zinc). In the meantime I’ll try not to worry, I’m doing a lot of things right :D
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Re: Scary DNAge result

Postby Tincup » Tue Sep 21, 2021 3:50 pm

vegarejuvinated wrote: I’ve read that these tests based on Horvaths clock are pretty accurate and I was keen to get a sense (and honestly felt like it would make me feel good



In this Peter Attia interview with Matt Kaeberlein they talk about these biomarkers and gave their opinions, which don't seem as positive as you might expect.

Biomarkers of aging and epigenetic clocks [1:29:15];

These are from the subscriber's podcast notes:

Biomarkers of aging and epigenetic clocks [1:29:15]
Aging biomarkers

What would biomarkers for aging look like?
When Peter had Eileen White on the podcast, she pointed out that we don’t even have biomarkers for something as important as autophagy
We don’t know how long a human should fast to generate a meaningful amount of autophagy (in mice it’s a day, and in humans 7 days is likely enough, but we don’t precisely know)
We can measure telomere length, but Peter does not think this is a helpful measurement for aging: “I think there’s plenty of data to suggest that while telomere length is a very important marker of cellular division, it really speaks very little about the organism’s state of aging”
Epigenetic clocks

Peter doesn’t think epigenetic clocks are useful either because they can easily be manipulated by short-term interventions that don’t seem biologically relevant
The epigenetic clock refers to chemical marks on DNA that regulate gene expression (whether or not a gene is turned on or off)
these marks change with age in pretty much every organism where it’s been studied
We have identified patterns of change at specific locations in the genome that correlate very strongly with chronological age
So we have tried to create clocks that look at specific chemical marks in the DNA to determine how long that that organism has been alive
You can identify individuals whose chemical marks are not in line with what we would expect given their chronological age
They seem to be aging faster or more slowly than expected
And indeed, those individuals who tend to be off the line turn out to be at lower or higher risk for specific diseases depending on whether they seem to be aging more slowly or more quickly
This adds some weight to the argument that epigenetic clocks are measuring biological age
Can we develop epigenetic clocks that will, in a predictive way, tell you how old you are biologically?
Some companies are selling these tests right now
Human tests are based on markers in the blood, but it’s not clear whether the “biological age” of the blood reflects the biological age of the entire body
They are mostly looking at peripheral blood mononuclear cells (PBMCs) and maybe saliva tests, but Matt’s not sure how the commercial companies are doing it
Peter discounts clocks that use inputs like glucose or vitamin D level, because they vary widely from day to day and are easy to manipulate
Matt thinks the data and correlations of epigenetic clocks are strong
But he’s skeptical that there are so many data points in the epigenome that you can find a pattern that will fit pretty much anything you look for
It may not be a robust predictor of biological age, but they are telling us something
Peter would like to have Steve Horvath on the podcast to talk about the details of data from epigenetic clocks
Matt says that people are now “going beyond the epigenetic clocks to try to look at every possible thing you could measure, sometimes combining that with the epigenetic clock to build these multi-element clocks”
Now you have tens of thousands of additional data points, which makes it more likely you can find a pattern
We’re not yet at the point of getting to biological explanations for what the patterns are telling us
Are the genes at the mark locations causal for biological aging in any way? We’d need to understand the mechanism to know
“We have a lot of biomarkers of aging. We just don’t have any validated biomarkers of aging. …You can identify all sorts of things that correlate with age. How do you get to the point of convincing yourself … that these things are actually telling you something about biological aging that can then be used to understand whether an intervention is working?’” —Matt Kaeberlein

The goal would be to develop a test you could take to find out if something you are doing (fasting, taking metformin or rapamycin, etc.) is working based on a set of biomarkers
We are not there yet


Prospects of a test that could calculate biological age [1:37:45]
Steve Austad was recently on the podcast and made a similar point about the ITP studies
They out a lot of time and money into it, but you can argue that the technology simply wasn’t mature enough
Now, 30 years later, we have “omics,” machine learning, etc.
Maybe it could be done today, but it might be too disjointed a project for academia
But it’s not a particularly good commercial endeavor because you’d have to invest far too much up front before it would pay off
“someone’s got to pony up a lot of money to develop the foundation of a pyramid that will ultimately become a great tool for drug discovery”
Matt thinks there isn’t much of a barrier to doing it pre-clinically now
You could do a multiomic analysis of aging in mice
Apply machine learning to identify patterns that predict the effect of interventions and individual outcomes for longevity
Would be restricted to looking at blood if wanted to do a longitudinal study because you could not kill the animals
The biotech company Calico has the resources and expertise to do this kind of study
They are interested in multiomic signatures of different aging processes
They’re a kind of hybrid between academia and industry
You could develop a test of, say, 24 factors that give you 95% confidence on remaining life
Then you could do an independent study to see if it works
It would be really impressive if you could predict how long mice would live at the individual level when they are 6 months old, and even more impressive to show that a specific intervention can predict they’re going to live 30% longer
But you can’t use this approach in humans
It takes a long time to do the validation step and know that you have actually changed somebody’s biological state so that they are at lower risk for disease and are likely to live some X percent longer
You are almost obligated to have some level of faith in the test at that point
It’s not clear what you’d have to do before you could convince regulators that you can actually go out and tell the general public that this test works (although they are not really stopping people who are already doing that)
Tincup
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Re: Scary DNAge result

Postby vegarejuvinated » Sat Sep 25, 2021 3:28 pm

Tincup wrote:In this Peter Attia interview with Matt Kaeberlein they talk about these biomarkers and gave their opinions, which don't seem as positive as you might expect.


Thanks Tincup, I am an avid listener of Peter Attia as as you can imagine I was really interested in this episode. I don’t remember whether it was in this one but I remember Peter talking about a 5yr variance in a single day depending up a variety of things including hydration and nutrient status. I have never heard anyone even in podcasts with Steve Horvath discuss at 20+ year variance.

I’m going to to go and get some further blood tests on Monday. Anything you think I should specifically look at?
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Re: Scary DNAge result

Postby giftsplash » Fri Oct 08, 2021 7:24 pm

I would not be too concerned. I do not know what biomarkers made you seem older but what ever they are they can usually be fixed.

If you have your basic CBC test, and CRP from your last physical you can use those numbers with the Levine epigenetic clock.

https://www.oliverzolman.com/phenoage-calculator


Or if you have more data you can use Aging.AI clock

http://www.aging.ai/


I have been optimizing my diet to try to lower my epigenetic clock scores for the last year and the correlation between the 2 clocks I listed above are less than 0.5


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